US2014315255A1PendingUtilityA1
Novel antibacterial compounds, methods of making them, and uses thereof
Est. expiryJul 9, 2030(~3.9 yrs left)· nominal 20-yr term from priority
A61P 31/04A61P 43/00A61P 17/00C07H 5/06C07H 15/252C12P 19/28A61K 31/7056A61K 31/706A61K 31/7048A61P 17/02C12P 7/66A61P 11/00A61K 31/015A61K 31/704A61K 31/35C07C 50/22C12R 2001/465C12N 1/205
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Claims
Abstract
The present invention relates to novel therapeutics with antibacterial activity, processes for their preparation, and pharmaceutical, veterinary and nutritional compositions containing them as active ingredients. The present invention also relates to uses of the novel therapeutics, for example, as medicants or food additives in the treatment of bacterial infections or to aid body mass gain in a subject.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1 . A method for making a product compound having the formula:
said method comprising:
fermenting a culture medium comprising Streptomyces strain AMRI-7957 (ATCC Accession No. PTA-11098) under conditions effective to produce a fermentation broth comprising the product compound, and
isolating the product compound.
2 . The method according to claim 1 , wherein fermenting comprises:
culturing Streptomyces strain AMRI-7957 (ATCC Accession No. PTA-11098), and inoculating the culture into a fermentor.
3 . The method according to claim 1 , wherein isolating comprises:
separating the fermentation broth into a biomass fraction and a supernatant fraction.
4 . The method according to claim 3 , wherein isolating comprises:
extracting the product compound from the biomass fraction.
5 . The method according to claim 3 , wherein isolating comprises:
extracting the product compound from the supernatant fraction.
6 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate compound having the structure
under conditions effective to form the product compound.
7 . The method according to claim 6 , wherein treating comprises reacting the first intermediate with R 1 Z 1 , wherein Z 1 is a halide.
8 . A method of making a product compound of formula I
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate compound having the structure:
under conditions effective to form the product compound.
9 . The method according to claim 8 , wherein treating comprises reacting the first intermediate with R 2 Z 2 , wherein Z 2 is a halide or H.
10 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate compound having the structure:
under conditions effective to form the product compound.
11 . The method according to claim 10 , wherein treating comprises reacting the first intermediate compound with N—R 3 -succinimide.
12 . The method according to claim 10 , wherein R 3 is NO 2 and treating comprises reacting the first intermediate with a nitration agent.
13 . The method according to claim 12 , wherein the nitration agent is zirconyl(IV) nitrate hydrate.
14 . The method according to claim 12 further comprising:
reacting the product compound with a reducing agent.
15 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , (CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate having the structure:
under conditions effective to form the product compound.
16 . The method according to claim 15 , wherein R 4 is ═NR 14 and treating comprises reacting the first intermediate with NH 2 R 14 .
17 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate having the structure:
under conditions effective to form the product compound.
18 . The method according to claim 17 , wherein treating comprises reacting the first intermediate compound with R 5 Z 1 , wherein Z 1 is a halide.
19 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of (CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —N 12 R 13 , (CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , (CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate having the structure:
under conditions effective to form the product compound.
20 . The method according to claim 19 , wherein X is N and treating comprises reacting the first intermediate with NH 2 R 6 .
21 . The method according to claim 19 further comprising:
reacting the product compound with a coupling agent such that R 5 and R 6 combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy.
22 . The method according to claim 21 , wherein the coupling agent is carbonyldiimidazole.
23 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , (CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate having the structure
under conditions effective to form the product compound.
24 . The method according to claim 23 , wherein treating comprises reacting the first intermediate compound with N—R 7 -succinimide.
25 . The method according to claim 23 , wherein R 7 is —NO 2 and treating comprises reacting the first intermediate with a nitration agent.
26 . The method according to claim 25 , wherein the nitration agent is zirconyl(IV) nitrate hydrate.
27 . The method according to claim 25 further comprising:
reacting the product compound with a reducing agent.
28 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate having the structure:
under conditions effective to form the product compound.
29 . The method according to claim 28 , wherein treating comprises reacting the first intermediate with R 8 -M-L, wherein M is a metal and L is a halide.
30 . The method according to claim 28 , wherein treating comprises reacting the first intermediate with R 9 -M-L, wherein M is a metal and L is a halide.
31 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate having the structure:
under conditions effective to form the product compound.
32 . The method according to claim 31 , wherein Y is N and treating comprises reacting the first intermediate with NH 2 R 10 .
33 . A method of making a product compound of formula I:
wherein:
the carbohydrate anomeric carbon designated * is in the R or S configuration;
R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, heteroarylalkyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , or —NR 12 R 13 ;
R 2 is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 3 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 4 is selected from the group consisting of H, halogen, —OR 12 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , phenyl, benzyl, ═NOR 14 , ═NR 14 , a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 6 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —NR 12 R 13 , —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n (O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
or R 5 and R 6 can combine to form a heterocycle group containing from 1 to 5 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur and optionally substituted 1 to 3 times with halogen, oxo, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 7 is selected from the group consisting of H, halogen, —OR 12 , —NR 12 R 13 , —NR 12 C(O)R 13 , —NR 12 C(O) 2 R 13 , —NR 12 C(O)NR 12 R 13 , —S(O) q R 12 , —CN, —NO 2 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , an amino acid group, and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 12 , or —NR 12 R 13 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —OR 12 , phenyl, benzyl, a benzyl ether moiety, a carbamate moiety, and a carbonate moiety, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 8 and R 9 can combine to form an oxo, thio, imine, or an ═NR 14 moiety;
R 10 is optionally present and, if present, is selected from the group consisting of H, —OR 12 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, benzyl, a carbohydrate, a benzyl ether moiety, a carbamate moiety, an ═NR 14 moiety, and a carbonate moiety, wherein each of —(CH 2 ) n C(O)R 11 , —(CH 2 ) n C(O)NR 12 R 13 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, —NO 2 , —NR 12 R 13 , —OR 12 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 11 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 12 and R 13 are each independently selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n NR 16 R 17 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 16 R 17 , —(CH 2 ) n OC(O)NR 16 R 17 , —(CH 2 ) n NR 16 C(O)OR 17 , —(CH 2 ) n NC(O)NR 16 R 17 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, OH, C 1 -C 4 alkoxy, an amino acid group, or [NR 11 C(O)(CH 2 ) n ] m NR 16 R 17 , which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy, aryl alkyl, wherein the C 1 -C 4 alkyl and the aryl alkyl substituents are optionally substituted 1 to 3 times with halogen, alkyl, OH, NH 2 , —CO 2 H, —C(O)NH 2 , —NHC(O)NH 2 , —NHC(NH)NH 2 , imidazole, pyrolidine, SMe, SH, or SeH;
or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
R 14 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —S(O) q R 12 , —(CH 2 ) n NR 12 R 13 , —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —(CH 2 ) n C(O)R 11 , —(CH 2 ) n OC(O)R 11 , —(CH 2 ) n C(O) 2 R 11 , —(CH 2 ) n C(O)NR 12 R 13 , —(CH 2 ) n OC(O)NR 12 R 13 , —(CH 2 ) n NR 11 C(O)OR 12 , —(CH 2 ) n NC(O)NR 12 R 13 , aryl, heteroaryl, arylalkyl, and heteroarylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C 1 -C 3 alkyl, halogen, —CN, —OR 12 , —NR 12 R 13 , and phenyl which is optionally substituted 1-3 times with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —NO 2 , —OR 12 , —NR 12 R 13 , or an amino acid group;
R 15 is H, C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, or phenyl, wherein each of C 1 -C 4 alkyl, arylalkyl, heteroarylalkyl C 1 -C 4 haloalkyl, and phenyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, or an amino acid group;
R 16 and R 17 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 15 , —C(O)OR 15 , phenyl, or benzyl, wherein each of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, and benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, and an amino acid group;
or R 16 and R 17 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which may be saturated or unsaturated and comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
X is O or N;
Y is O or N;
m is 0, 1, 2, or 3;
n is 0 to 5;
q is 0, 1, or 2; and
represents an optional double bond;
said method comprising:
treating a first intermediate having the structure:
under conditions effective to form the product compound.
34 . The method according to claim 33 , wherein treating comprises reacting the first intermediate with an imidate having a formula:
35 . The method according to claim 34 , wherein the imidate isJoin the waitlist — get patent alerts
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