US2003144501A1PendingUtilityA1
Conformationally constrained L-nucleosides
Priority: May 11, 1999Filed: Feb 14, 2003Published: Jul 31, 2003
Est. expiryMay 11, 2019(expired)· nominal 20-yr term from priority
Inventors:Kanda Ramasamy
C07H 19/056C07H 19/04
52
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Claims
Abstract
L-nucleosides are conformationally constrained by at least one additional ring formed by a bridge connecting at least two atoms within a sugar moiety of the nucleoside. While a single additional ring is formed by bridging C 1 -C 4 atoms, two additional rings are formed by bridging both C 1 -C 2 , and C 3 -C 4 atoms, or C 1 -C 3 and C 2 -C 4 atoms by bridges having the general structure A—B—Z. The conformationally constrained nucleosides may be incorporated into oligonucleotides and dinucleotides, and it is contemplated that compositions including the conformationally constrained nucleosides may have superior viral inhibitory or antineoplastic properties.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A nucleoside having a nucleobase glycosidically bound to a sugar moiety wherein the sugar moiety has an L-configuration and has at least one additional ring that is formed via a bridge connecting a first and a second atom in the sugar moiety, wherein the first and the second atom are separated by at least a third atom in the sugar moiety.
2 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n , or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
wherein no more than two of A, B, and Z are an atom other than a carbon atom; and
R 2 and R 3 are independently H, OH, OPO 3 2− , CN, halogen, N 3 , CH 2 OH, methylidene, lower alkyl or lower alkyl amine, and R 4 is H, OH, OPO 3 2− .
3 . The nucleoside of claim 2 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 2 , R 3 , R 4 , and B.
4 . The nucleoside of claim 3 wherein the nucleoside is covalently coupled to an oligonucleotide to form a modified oligonucleotide.
5 . The nucleoside of claim 4 wherein the coupling to the oligonucleotide is on at least one of a 5′-end and a 3′-end of the oligonucleotide.
6 . The nucleoside of claim 3 wherein the nucleoside is covalently coupled to a mononucleotide to form a modified dinucleotide.
7 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n , or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
R 1 is H, OH, or OPO 3 2− ; and
wherein no more than two of A, B, and Z are an atom other than a carbon atom.
8 . The nucleoside of claim 7 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 and B.
9 . The nucleoside of claim 8 wherein the nucleoside is covalently coupled to an oligonucleotide to form a modified oligonucleotide.
10 . The nucleoside of claim 9 wherein the coupling to the oligonucleotide is on at least one of a 5′-end and a 3′-end of the oligonucleotide.
11 . The nucleoside of claim 8 wherein the nucleoside is covalently coupled to a mononucleotide to form a modified dinucleotide.
12 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
R 1 is H, OH, or OPO 3 2− ; and
wherein no more than two of A, B, and Z are an atom other than a carbon atom.
13 . The nucleoside of claim 12 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 and B.
14 . The nucleoside of claim 13 wherein the nucleoside is covalently coupled to an oligonucleotide to form a modified oligonucleotide.
15 . The nucleoside of claim 14 wherein the coupling to the oligonucleotide is on at least one of a 5′-end and a 3′-end of the oligonucleotide.
16 . The nucleoside of claim 13 wherein the nucleoside is covalently coupled to a mononucleotide to form a modified dinucleotide.
17 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CHOH, CH 2 or N—COCH 3 ;
R 1 is H, OH, or OPO 3 2− ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n , or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
wherein no more than two of A, B, and Z are an atom other than a carbon atom;
E is O, S, (CH 2 ) n , N—R, or nothing, and when both F and G are independently O, S or N—R then E is (CH 2 ) n , wherein R is H, OH, CO—, lower alkyl or COCH 3 , and n is 1-5;
F and G are independently O, S, (CH 2 ) n , or N—R, and when both E and F are independently O, S or N—R then G is (CH 2 ) n , wherein R is H, OH, CO—, lower alkyl or COCH 3 , and n is 1-5; and
wherein no more than two of E, F, and G are an atom other than a carbon atom.
18 . The nucleoside of claim 17 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 and B.
19 . The nucleoside of claim 18 wherein the nucleoside is covalently coupled to an oligonucleotide to form a modified oligonucleotide.
20 . The nucleoside of claim 19 wherein the coupling to the oligonucleotide is on at least one of a 5′-end and a 3′-end of the oligonucleotide.
21 . The nucleoside of claim 18 wherein the nucleoside is covalently coupled to a mononucleotide to form a modified dinucleotide.
22 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n , or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
R 1 and R 2 is independently H, OH, or OPO 3 2− ; and
wherein no more than two of A, B, and Z are an atom other than a carbon atom.
23 . The nucleoside of claim 22 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 , R 2 and B.
24 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n , or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
R 1 and R 2 is independently H, OH, or OPO 3 2− ; and
wherein no more than two of A, B, and Z are an atom other than a carbon atom.
25 . The nucleoside of claim 24 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 , R 2 and B.
26 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ; and
R 1 and R 2 is independently H, OH, or OPO 3 2− .
27 . The nucleoside of claim 26 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 and R 2 .
28 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n , or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
R 1 and R 2 is independently H, OH, or OPO 3 2− ; and
wherein no more than two of A, B, and Z are an atom other than a carbon atom.
29 . The nucleoside of claim 28 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 and R 2 .
30 . The nucleoside of claim 1 having the structure:
wherein
Base is a nucleobase covalently bound to the C 1 -atom via a nitrogen- or carbon atom in the nucleobase;
X is O, S, CHOH, CH 2 or N—COCH 3 ;
A is O, S, (CH 2 ) n , N—R, or nothing, and when both B and Z are independently O, S or N—R then A is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
B and Z are independently O, S, (CH 2 ) n , or N—R, and when both A and B are independently O, S or N—R then Z is (CH 2 ) n , wherein R is H, OH, CO—, OPO 3 2− , lower alkyl or COCH 3 , and n is 1-5;
R 1 and R 2 is independently H, OH, or OPO 3 2− ; and
wherein no more than two of A, B, and Z are an atom other than a carbon atom.
31 . The nucleoside of claim 30 wherein the nucleoside is covalently coupled to at least one nucleotide, and wherein the covalent coupling involves at least one of R 1 and R 2 .Join the waitlist — get patent alerts
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