US2009239873A1PendingUtilityA1
Phenyl-piperazine derivatives as modulators of muscarinic receptors
Assignee: BLANCO MIGUEL GARCIA-GUZMANPriority: Sep 26, 2003Filed: Dec 31, 2008Published: Sep 24, 2009
Est. expirySep 26, 2023(expired)· nominal 20-yr term from priority
Inventors:Miguel Garcia-Guzman BlancoDaniele BergeronPeter GrootenhuisDennis HurleyAkiko NakataniLewis R. MakingsDaniel DisepioGabriel Raffai
A61P 43/00A61P 9/06A61P 27/02A61P 3/04A61P 25/00A61P 25/28A61P 25/24A61P 25/14A61P 25/04A61P 27/06A61P 25/18A61P 25/16A61P 1/00A61P 17/02A61P 1/02A61P 11/06C07D 451/02A61K 31/495C07D 295/073C07D 295/096C07D 295/155A61K 31/496C07D 211/58C07D 451/04C07D 295/135C07D 309/14C07D 493/08C07D 295/033A61K 31/196
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Claims
Abstract
The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases.
Claims
exact text as granted — not AI-modified1 . A method of modulating activity of a muscarinic receptor, comprising the step of contacting said receptor with a compound having the formula:
wherein:
B is selected from
D is CF 2 , CH 2 , or CHR 9 ;
Ring C is phenyl optionally substituted with 1 to 4 of R 1 , R 2 , R 3 , R 4 , or R 5 ;
Ring A is a 3-8 membered monocyclic carbocyclic ring, a 7-14 membered bicyclic carbocyclic ring, a 7-14 tricyclic carbocyclic ring, a 3-8 membered monocyclic heterocyclic ring, a 7-14 membered bicyclic, heterocyclic ring, or a 7-14 tricyclic heterocyclic ring, in which the heterocyclic rings contain 1-5 atoms selected from O, S, and N;
wherein ring A contains up to 5 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 ;
Each R 1 is independently oxo or ((C1-C4)aliphatic) m -Q 1 ;
Each Q 1 is independently halo, CN, NO 2 , CF 3 , OCF 3 , OH, SR 6 , S(O)R 6 , SO 2 R 6 , N(R 6 ) 2 , NR 6 R 8 , COOH, COOR 6 or OR 6 ;
Each R 2 is independently aliphatic optionally substituted with 1-3 substituents independently selected from R 1 , R 4 , or R 5 ;
Each R 3 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1-3 substituents independently selected from R 1 , R 2 , R 4 , or R 5 ;
Each R 4 is independently OR 5 , OR 6 , OC(O)R 6 , OC(O)R 5 , OC(O)OR 6 , OC(O)OR 5 , OC(O)N(R 6 ) 2 , OC(O)N(R 5 ) 2 , OC(O)N(R 6 R 5 ), S(O) i R 6 , S(O) i R 5 , SO 2 N(R 6 ) 2 , SO 2 N(R 5 ) 2 , SO 2 NR 5 R 6 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , C(O)N(R 5 R 6 ), C(O)N(OR 6 )R 6 , C(O)N(OR 5 )R 6 , C(O)N(OR 6 )R 5 , C(O)N(OR 5 )R 5 , C(NOR 6 )R 6 , C(NOR 6 )R 5 , C(NOR 5 )R 6 , C(NOR 5 )R 5 , N(R 6 ) 2 , N(R 5 ) 2 , N(R 5 R 6 ), NR 5 C(O)R 5 , NR 6 C(O)R 6 , NR 6 C(O)R 5 , NR 6 C(O)OR 6 , NR 5 C(O)OR 6 , NR 6 C(O)OR 5 , NR 5 C(O)OR 5 , NR 6 C(O)N(R 6 ) 2 , NR 6 C(O)NR 5 R 6 , NR 6 C(O)N(R 5 ) 2 , NR 5 C(O)N(R 6 ) 2 , NR 5 C(O)NR 5 R 6 , NR 5 C(O)N(R 5 ) 2 , NR 6 SO 2 R 6 , NR 6 SO 2 R 5 , NR 5 SO 2 R 5 , NR 6 SO 2 N(R 6 ) 2 , NR 6 SO 2 NR 5 R 6 , NR 6 SO 2 N(R 5 ) 2 , NR 5 SO 2 NR 5 R 6 , NR 5 SO 2 N(R 5 ) 2 , N(OR 6 )R 6 , N(OR 6 )R 5 , N(OR 5 )R 5 , or N(OR 5 )R 6 ;
Each R 5 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1 to 3 of R 1 ;
Each R 6 is independently H or aliphatic optionally substituted with R 7 ;
Each R 7 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1 to 2 of (C 1 -C 6 )-straight or branched alkyl, (C 2 -C 6 ) straight or branched alkenyl or alkynyl, 1,2-methylenedioxy, 1,2-ethylenedioxy, or (CH 2 ) n -Q 2 ;
Each Q 2 is independently selected from halo, CN, NO 2 , CF 3 , OCF 3 , OH, S-aliphatic, S(O)-aliphatic, SO 2 -aliphatic, COOH, C(O)O-aliphatic, or O-aliphatic;
Each R 8 is independently an amino protecting group;
Each R 9 is independently R 2 , R 3 , or R 6 ;
Each i is independently 0, 1, 2, or 3;
Each m is independently 0 or 1; and
Each n is independently 0 or 1; further provided that
(i) when n is 1, D is CH 2 , C is phenyl, and B is piperazine then ring A is not
(ii) when n is 1, D is CH 2 , C is phenyl, and B is piperazine then ring A is not
(iii) when n is 0, C is phenyl, and B is piperazine then ring A is not
(iv) when n is 1, D is CH 2 , ring A is 1,2,3,4 tetrahydroquinoline optionally substituted with R 4 , and B is piperazine, then C is not phenyl substituted with halo, phenyl substituted with —OCH 3 , or phenyl substituted with halo and —OCH 3 ;
(v) when n is 1, D is CH 2 , ring A is
in which R 20 is —C(O)R5, —C(O)R6, —C(O)OR5, C(O)OR6, and B is piperazine, then C is not phenyl optionally substituted with halo or —OCH 3 .
2 . The method according to claim 1 , wherein D is CH 2 or CHR 9 .
3 . The method according to claims 1 , wherein D is CH 2 or CF 2 .
4 . The method according to claim 3 , wherein D is CH 2 .
5 . The method according to claim 2 , wherein D is CHR 9 .
6 . The method according to any one of claims 1 - 4 , wherein n is 0.
7 . The method according to any one of claims 1 - 4 , wherein n is 1.
8 . The method according to any one of claims 1 - 7 , wherein A is an monocyclic C3-C8 cycloaliphatic ring optionally substituted with 1-5 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 .
9 . The method according to claim 8 , wherein A is a cyclopropyl, cyclopentyl, cyclohexyl, or cycloheptyl, each optionally substituted with 1-5 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 .
10 . The method according to any one of claims 1 - 9 , wherein A is a bicyclic, bridged bicyclic or bridged tricyclic C7-C14 cycloaliphatic ring, each optionally substituted with 1-5 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 .
11 . The method according to claim 11 , wherein A is 1-adamantyl, 2-adamantyl, 1-norbornyl, or 1-bicyclo[2.2.1]hept-5-en-2-yl.
12 . The method according to any one of claims 1 - 8 , wherein A is a monocyclic, bicyclic, bridged bicyclic or bridged tricyclic C3-C12 heterocyclic ring, each optionally substituted with 1-5 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 , provided that ring A together with any substituent of ring A does not include a basic nitrogen atom.
13 . The method according to claim 12 , wherein A is selected from optionally substituted pyrrolidyl, tetrahydrofuranyl, tetrahydrothienyl, dioxolanyl, pyrrolinyl, pyranyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, or indolinyl, provided that ring A together with any substituent of ring A does not include a basic nitrogen atom.
14 . The method according to claim 1 , wherein A is
in which
X, Y, and Z 5 are each independently CR′;
X 1 and Y 1 are independently selected from a bond, CH 2 , CHR 9 , O, S, NR′, C(O), S(O), or SO 2 provided that both X 1 and Y 1 are not simultaneously a bond;
Z is C(R′) 2 , C(R′) 2 —C(R′) 2 , C(R′) 2 -Q, or Q, wherein Q is O, NR′, S(O), SO 2 , or C(O);
Each of Z 1 , Z 2 , Z 3 , and Z 4 is independently selected from CH 2 , CHR′, O, S, NR′, C(O), S(O), SO 2 ;
R′ is selected from (C1-C4)aliphatic) m -Q 1 , S(O) i R 6 , S(O) i R 5 , SO 2 N(R 6 ) 2 , SO 2 N(R 5 ) 2 , SO 2 NR 5 R 6 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , C(O)N(R 5 R 6 ), C(O)N(OR 6 )R 6 , C(O)N(OR 5 )R 6 , C(O)N(OR 6 )R 5 , C(O)N(OR 5 )R 5 , C(NOR 6 )R 6 , C(NOR 6 )R 5 , C(NOR 5 )R 6 , C(NOR 5 )R 5 , R 2 , or R 6 , provided that when any of X 1 , Y 1 , Z, Z 1 , Z 2 , Z 3 , and Z 4 are NR′, then R′ is S(O) i R 6 , S(O) i R 5 , SO 2 N(R 6 ) 2 , SO 2 N(R 5 ) 2 , SO 2 NR 5 R 6 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , C(O)N(R 5 R 6 ), C(O)N(OR 6 )R 6 , C(O)N(OR 5 )R 6 , C(O)N(OR 6 )R 5 , C(O)N(OR 5 )R 5 , C(NOR 6 )R 6 , C(NOR 6 )R 5 , C(NOR 5 )R 6 , C(NOR 5 )R 5 .
15 . The method according to claim 1 , wherein A is
optionally substituted with 1-3 of R′; in which
X 1 is independently selected from a bond, CH 2 , CHR 9 , O, S, NR′, C(O), S(O), SO 2 ;
R′ is selected from (C1-C4)aliphatic) m -Q 1 , S(O) i R 6 , S(O) i R 5 , SO 2 N(R 6 ) 2 , SO 2 N(R 5 ) 2 , SO 2 NR 5 R 6 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , C(O)N(R 5 R 6 ), C(O)N(OR 6 )R 6 , C(O)N(OR 5 )R 6 , C(O)N(OR 6 )R 5 , C(O)N(OR 5 )R 5 , C(NOR 6 )R 6 , C(NOR 6 )R 5 , C(NOR 5 )R 6 , C(NOR 5 )R 5 , R 2 , or R 6 , provided that when any of X 1 , Y 1 , Z, Z 1 , Z 2 , Z 3 , and Z 4 are NR′, then R′ is S(O) i R 6 , S(O) i R 5 , SO 2 N(R 6 ) 2 , SO 2 N(R 5 ) 2 , SO 2 NR 5 R 6 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , C(O)N(R 5 R 6 ), C(O)N(OR 6 )R 6 , C(O)N(OR 5 )R 6 , C(O)N(OR 6 )R 5 , C(O)N(OR 5 )R 5 , C(NOR 6 )R 6 , C(NOR 6 )R 5 , C(NOR 5 )R 6 , C(NOR 5 )R 5 ;
y is 0, 1, or 2;
z is 0, 1, or 2; and
bond r is optionally a single or double bond;
provided that when D is CH 2 , y is 1 and z is 2, that X1 is other than C(O) or —CH(OH)—.
16 . The method according to claim 1 , wherein B is piperazine.
17 . The method according to claim 1 , wherein said compound of formula (I) is selected from any one of compounds
18 . The method according to claim 1 , wherein said compound of formula (I) is selected from any one of compounds
19 . The method according to claim 1 , wherein said method is selective for at least one of M 1 and M 4 .
20 . The method according to claim 19 , wherein said method is selective for M 4 .
21 . The method according to claim 1 , wherein the modulation is activation.
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50 . A method of treating or reducing the severity of a muscarinic receptor mediated disease in a mammal, comprising the step of administering to said mammal a compound of Formula I:
wherein:
B is selected from
D is CF 2 , CH 2 , or CHR 9 ;
Ring C is phenyl optionally substituted with 1 to 4 of R 1 , R 2 , R 3 , R 4 , or R 5 ;
Ring A is a 3-8 membered monocyclic carbocyclic ring, a 7-14 membered bicyclic carbocyclic ring, a 7-14 tricyclic carbocyclic ring, a 3-8 membered monocyclic heterocyclic ring, a 7-14 membered bicyclic heterocyclic ring, or a 7-14 tricyclic heterocyclic ring, in which the heterocyclic rings contain 1-5 atoms selected from O, S, and N;
wherein ring A contains up to 5 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 ;
Each R 1 is independently oxo or ((C1-C4)aliphatic) m -Q1;
Each Q1 is independently halo, CN, NO 2 , CF 3 , OCF 3 , OH, SR 6 , S(O)R 6 , SO 2 R 6 , N(R 6 ) 2 , NR 6 R 8 , COOH, COOR 6 or OR 6 ;
Each R 2 is independently aliphatic optionally substituted with 1-3 substituents independently selected from R 1 , R 4 , or R 5 ;
Each R 3 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1-3 substituents independently selected from R 1 , R 2 , R 4 , or R 5 ;
Each R 4 is independently OR 5 , OR 6 , OC(O)R 6 , OC(O)R 5 , OC(O)OR 6 , OC(O)OR 5 , OC(O)N(R 6 ) 2 , OC(O)N(R 5 ) 2 , OC(O)N(R 6 R 5 ), S(O) i R 6 , S(O) i R 5 , SON(R 6 ) 2 , SO 2 N(R 5 ) 2 , SO 2 NR 5 R 6 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , C(O)N(R 5 R 6 ), C(O)N(OR 6 )R 6 , C(O)N(OR 5 )R 6 , C(O)N(OR 6 )R 5 , C(O)N(OR 5 )R 5 , C(NOR 6 )R 6 , C(NOR 6 )R 5 , C(NOR 5 )R 6 , C(NOR 5 )R 5 , N(R 6 ) 2 , N(R 5 ) 2 , N(R 5 R 6 ), NR 5 C(O)R 5 , NR 6 C(O)R 6 , NR 6 C(O)R 5 , NR 6 C(O)OR 6 , NR 5 C(O)OR 6 , NR 6 C(O)OR 5 , NR 5 C(O)OR 5 , NR 6 C(O)N(R 6 ) 2 , NR 6 C(O)NR 5 R 6 , NR 6 C(O)N(R 5 ) 2 , NR 5 C(O)N(R 6 ) 2 , NR 5 C(O)NR 5 R 6 , NR 5 C(O)N(R 5 ) 2 , NR 6 SO 2 R 6 , NR 6 SO 2 R 5 , NR 5 SO 2 R 5 , NR 6 SO 2 N(R 6 ) 2 , NR 6 SO 2 NR 5 R 6 , NR 6 SO 2 N(R 5 ) 2 , NR 5 SO 2 NR 5 R 6 , NR 5 SO 2 N(R 5 ) 2 , N(OR 6 )R 6 , N(OR 6 )R 5 , N(OR 5 )R 5 , or N(OR 5 )R 6 ;
Each R 5 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1 to 3 of R 1 ;
Each R 6 is independently H or aliphatic optionally substituted with R 7 ;
Each R 7 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1 to 2 of (C 1 -C 6 )-straight or branched alkyl, (C 9 -C 6 ) straight or branched alkenyl or alkynyl, 1,2-methylenedioxy, 1,2-ethylenedioxy, or (CH 2 ) n -Q 2 ;
Each Q2 is independently selected from halo, CN, NO 2 , CF 3 , OCF 3 , OH, S-aliphatic, S(O)-aliphatic, SO 2 -aliphatic, COOH, C(O)O-aliphatic, or O-aliphatic;
Each R 8 is independently an amino protecting group;
Each R 9 is independently R 2 , R 3 , or R 6 ;
Each i is independently 0, 1, 2, or 3;
Each m is independently 0 or 1; and
Each n is independently 0 or 1;
further provided that
(i) when n is 1, D is CH 2 , C is phenyl, and B is piperazine then ring A is not
(ii) when n is 1, D is CH 2 , C is phenyl, and B is piperazine then ring A is not
(iii) when n is 0, C is phenyl, and B is piperazine then ring A is not
(iv) when n is 1, D is CH 2 , ring A is 1, 2, 3, 4 tetrahydroquinoline optionally substituted with R 4 , and B is piperazine, then C is not phenyl substituted with halo, phenyl substituted with —OCH 3 , or phenyl substituted with halo and —OCH 3 ;
(v) when n is 1, D is CH 2 , ring A is
in which R 20 is —C(O)R5, —C(O)R6, —C(O)OR5, C(O)OR6, and B is piperazine, then C is not phenyl optionally substituted with halo or —OCH 3 .
51 . The method according to claim 50 , wherein said muscarinic receptor is M 4 .
52 . The method according to claim 50 , wherein said receptor is M 1 .
53 . A method of treating or reducing the severity of a disease in a patient, wherein said disease is selected from CNS derived pathologies including cognitive disorders, Attention Deficit Hyperactivity Disorder (ADHD), obesity, Alzheimer's disease, various dementias such as vascular dementia, psychosis associated with CNS disorders including schizophrenia, mania, bipolar disorders, pain conditions including acute and chronic syndromes, Huntington's Chorea, Friederich's ataxia, Gilles de la Tourette's Syndrome, Downs Syndrome, Pick disease, clinical depression, Parkinson's disease, peripheral disorders such as reduction of intra ocular pressure in Glaucoma and treatment of dry eyes and dry mouth including Sjögren's Syndrome, bradhycardia, gastric acid secretion, asthma, GI disturbances, and wound healing, wherein said method comprises the step of contacting said patient with a compound of Formula I:
wherein:
B is selected from
D is CF 2 , CH 2 , or CHR 9 ;
Ring C is phenyl optionally substituted with 1 to 4 of R 1 , R 2 , R 3 , R 4 , or R 5 ;
Ring A is a 3-8 membered monocyclic carbocyclic ring, a 7-14 membered bicyclic carbocyclic ring, a 7-14 tricyclic carbocyclic ring, a 3-8 membered monocyclic heterocyclic ring, a 7-14 membered bicyclic heterocyclic ring, or a 7-14 tricyclic heterocyclic ring, in which the heterocyclic rings contain 1-5 atoms selected from O, S, and N;
wherein ring A contains up to 5 substituents independently selected from R 1 , R 2 , R 3 , R 4 , or R 5 ;
Each R 1 is independently oxo or ((C1-C4)aliphatic) m -Q 1 ;
Each Q 1 is independently halo, CN, NO 2 , CF 3 , OCF 3 , OH, SR 6 , S(O)R 6 , SO 2 R 6 , N(R 6 ) 2 , NR 6 R 8 , COOH, COOR 6 or OR 6 ;
Each R 2 is independently aliphatic optionally substituted with 1-3 substituents independently selected from R 1 , R 4 , or R 5 ;
Each R 3 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1-3 substituents independently selected from R 1 , R 2 , R 4 , or R 5 ;
Each R 4 is independently OR 5 , OR 6 , OC(O)R 6 , OC(O)R 5 , OC(O)OR 6 , OC(O)OR 5 , OC(O)N(R 6 ) 2 , OC(O)N(R 5 ) 2 , OC(O)N(R 6 R 5 ), S(O) i R 6 , S(O) i R 5 , SO 2 N(R 6 ) 2 , SO 2 N(R 5 ) 2 , SO 2 NR 5 R 6 , C(O)R 5 , C(O)OR 5 , C(O)R 6 , C(O)OR 6 , C(O)N(R 6 ) 2 , C(O)N(R 5 ) 2 , C(O)N(R 5 R 6 ), C(O)N(OR 6 )R 6 , C(O)N(OR 5 )R 6 , C(O)N(OR 6 )R 5 , C(O)N(OR 5 )R 5 , C(NOR 6 )R 6 , C(NOR 6 )R 5 , C(NOR 5 )R 6 , C(NOR 5 )R 5 , N(R 6 ) 2 , N(R 5 ) 2 , N(R 5 R 6 ), NR 5 C(O)R 5 , NR 6 C(O)R 6 , NR 6 C(O)R 5 , NR 6 C(O)OR 6 , NR 5 C(O)OR 6 , NR 6 C(O)OR 5 , NR 5 C(O)OR 5 , NR 6 C(O)N(R 6 ) 2 , NR 6 C(O)NR 5 R 6 , NR 6 C(O)N(R 5 ) 2 , NR 5 C(O)N(R 6 ) 2 , NR 5 C(O)NR 5 R 6 , NR 5 C(O)N(R 5 ) 2 , NR 6 SO 2 R 6 , NR 6 SO 2 R 5 , NR 5 SO 2 R 5 , NR 6 SO 2 N(R 6 ) 2 , NR 6 SO 2 NR 5 R 6 , NR 6 SO 2 N(R 5 ) 2 , NR 5 SO 2 NR 5 R 6 , NR 5 SO 2 N(R 5 ) 2 , N(OR 6 )R 6 , N(OR 6 )R 5 , N(OR 5 )R 5 , or N(OR 5 )R 6 ;
Each R 5 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1 to 3 of R 1 ;
Each R 6 is independently H or aliphatic optionally substituted with R 7 ;
Each R 7 is independently a cycloaliphatic, aryl, heterocyclic, or heteroaryl ring, wherein each of the cycloaliphatic, aryl, heterocyclic, or heteroaryl are optionally substituted with 1 to 2 of (C 1 -C 6 )-straight or branched alkyl, (C 2 -C 6 ) straight or branched alkenyl or alkynyl, 1,2-methylenedioxy, 1,2-ethylenedioxy, or (CH 2 ) n -Q 2 ;
Each Q 2 is independently selected from halo, CN, NO 2 , CF 3 , OCF 3 , OH, S-aliphatic, S(O)-aliphatic, SO 2 -aliphatic, COOH, C(O)O-aliphatic, or O-aliphatic;
Each R 8 is independently an amino protecting group;
Each R 9 is independently R 2 , R 3 , or R 6 ;
Each i is independently 0, 1, 2, or 3;
Each m is independently 0 or 1; and
Each n is independently 0 or 1;
further provided that
(i) when n is 1, D is CH 2 , C is phenyl, and B is piperazine then ring A is not
(ii) when n is 1, D is CH 2 , C is phenyl, and B is piperazine then ring A is not
(iii) when n is 0, C is phenyl, and B is piperazine then ring A is not
(iv) when n is 1, D is CH 2 , ring A is 1,2,3,4 tetrahydroquinoline optionally substituted with R 4 , and B is piperazine, then C is not phenyl substituted with halo, phenyl substituted with —OCH 3 , or phenyl substituted with halo and —OCH 3 ;
(v) when n is 1, D is CH 2 , ring A is
in which R 20 is —C(O)R5, —C(O)R6, —C(O)OR5, C(O)OR6, and B is piperazine, then C is not phenyl optionally substituted with halo or —OCH 3 .Join the waitlist — get patent alerts
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