US 11,529,341 B2Granted

Bicyclic compounds as inhibitors of PD1/PD-L1 interaction/activation

OwnerChandregowda Venkateshappa, Jeyaraj D A +3inventors

InventorsChandregowda Venkateshappa, Jeyaraj D A, Muralidhar Pendyala, Dhanalakshmi Sivanandhan, Sridharan Rajagopal

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Abstract

The compounds of Formula I is described herein along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof. The compounds described herein, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof are bicyclic compounds that are inhibitors of PD-1/PD-L1 interaction/activation.

Claims15

Dependent claims

A compound of Formula I

their stereoisomers and pharmaceutically acceptable salts thereof,
wherein, X1 is selected from —CH2O— or —OCH2—;
R4 is hydrogen;
X is selected from CR3 or N;
R1, R2, R3, R6, and R7 are independently selected from hydrogen, halo, C1-6 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl-, and C(O)ORa, wherein the C1-6 alkyl and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, are independently optionally substituted with 1, 2, or 3 Rb substituents;
Ra is selected from hydrogen, C1-6 alkyl, C1-4 haloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, or (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein, the C1-6 alkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl- and (4-10 membered heterocycloalkyl)-C1-4 alkyl- are independently optionally substituted with 1, 2, or 3 Rd substituents;
Rb is selected from hydroxy, amino, C1-4 alkyl, 4-10 membered heterocycloalkyl, ORc, C(O)NRcRc, C(O)ORc, NHRc, NRcRc, or NRcC(O)Rc;
wherein, the C1-4 alkyl and 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 Rd substituents;
Rc is selected from hydrogen, C1-6 alkyl, or C3-10 cycloalkyl, wherein, the C1-6 alkyl and C3-10 cycloalkyl are optionally substituted with 1, 2, or 3 Rf substituent;
Rd is selected from cyano, C1-6 alkyl, halo, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C(O)NRcRc, or C(O)ORc, wherein, the C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 Rf substituents;
Rf is selected from C1-4 alkyl, halogen, CN, C(O)NRgRg, C(O)ORg, or NRgC(O)Rg;
Rg is selected from hydrogen or C1-6 alkyl;
m is 1 or 2;
Ring A is substituted or unsubstituted C6-10 aryl, substituted with C1-4 alkyl, cyano, or C1-4 haloalkyl;
Ring B is selected from C6-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

12 more elements

A compound or its stereoisomers and pharmaceutically acceptable salts thereof, selected from a group consisting of:

(S)-1-((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl) piperidine-2-carboxylic acid (1),
N-(2-(((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl) methyl)amino)ethyl)acetamide (2),
(S)-1-((7-((3-(1-(3-(3,3-difluoropyrrolidin-1-yl)propyl)-1H-indol-4-yl)-2-methylbenzyl)oxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (3),
(S)-1-((6-methyl-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (4),
(S)-1-((6-chloro-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (5),
Methyl 7-(((2-acetamidoethyl)amino)methyl)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-indene-5-carboxylate (6),
(S)-1-((7-((3′-(3-(3,3-difluoropyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (7), (S)-1-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (8),
(S)-1-((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (9)
N-(2-(((5-((5-fluoropyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (10)
(S)-5-((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (11)
(S)-1-((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-5-(2,2,2-trifluoroethoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (12)
N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)-N-methylacetamide (13)
N-(2-(((5-(1-(3-cyanophenyl)ethoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (14)
N-(1-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidin-3-yl)acetamide (15)
N-(2-(((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (16)
6-((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-2-oxa-6-azaspiro[3.3]heptane (17)
2-(hydroxymethyl)-2-(((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)propane-1,3-diol (18)
1-(((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)cyclopropane-1-carboxylic acid (19)
((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)glycine (20)
3-(((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)propanoic acid (21)
N-methyl-N-((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)glycine (22)
3-(((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)butanoic acid (23)
((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)alanine (24)
(2S,4R)-4-hydroxy-1-((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (25)
(S)-1-((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (26)
1-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)piperidine-2-carboxylic acid (27)
N-(2-(((6-methyl-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (28)
(2S,4R)-4-hydroxy-1-((6-methyl-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (29)
N-(2-(((6-chloro-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (30)
(2S,4R)-1-((6-chloro-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (31)
N-(2-(((7-((3′-(3-(3,3-difluoropyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (32)
(2S,4R)-1-((7-((3′-(3-(3,3-difluoropyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (33)
N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (34)
(2S,4R)-1-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (35)
(S)-1-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (36)
(S)-1-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxamide (37)
3-(((4-(((1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)benzonitrile (38)
3-(((4-((2-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)benzonitrile (39)
3-(((4-((3-hydroxypiperidin-1-yl)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)benzonitrile (40)
((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)glycine (41)
(S)-5-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (42)
rac-(1R,6S)-2-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl) dihydro-1H-inden-4-yl)methyl)-2-azabicyclo[4.1.0]heptane-1-carboxylic acid (cis, racemic) (43)
4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)butanoic acid (44)
(1R,6S)-2-((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl) methyl)-2-azabicyclo [4.1.0]heptane-1-carboxylic acid (cis, racemic) (45)
(S)-1-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (46)
(2S,4R)-1-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (47)
N-(2-(((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (48)
5-(((4-(((1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)nicotinonitrile (49)
(S)-4-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)morpholine-3-carboxylic acid (50)
rac-(1R,6S)-2-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methy 1-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-2-azabicyclo[4.1.0]heptane-1-carboxylic acid (cis, racemic) (51)
(S)-5-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (52)
N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)(methyl)amino)ethyl)acetamide (53)
N-(2-(((5-((4-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (54)
(S)-1-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (55)
N-(2-(((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (56)
(2S,4R)-1-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (57)
3-(((7-(((1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)-6-methoxy-2,3-dihydro-1H-inden-4-yl)oxy)methyl)-[1,1′-biphenyl]-2-carbonitrile (58)
(S)-4-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)morpholine-3-carboxylic acid (59)
((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)glycine (60)
(S)-5-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (61)
rac-(1R,6S)-2-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)-2-azabicyclo[4.1.0]heptane-1-carboxylic acid (cis, racemic) (62)
2-(1-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)piperidin-2-yl)acetic acid (63)
N-(2-(((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)(methyl)amino)ethyl)-N-methylacetamide (64)
5-((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)pentanoic acid (65)
5-((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)pentanamide (66)
(S)-1-((5-(4-carboxybutoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (67)
(S)-1-((5-((5-amino-5-oxopentyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (68)
(S)-1-((5-((5-cyanopyridin-3-yl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (69)
(2S,4R)-1-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (70)
(R)-1-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-3-carboxylic acid (71)
rac-(1R,6S)-2-((7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-5-((5-cyanopyridin-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-2-azabicyclo[4.1.0]heptane-1-carboxylic acid (cis racemic) (72)
Methyl 4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)bicyclo[2.2.2]octane-1-carboxylate (73)
4-(((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)bicyclo[2.2.2]octane-1-carboxylic acid (74)
(S)-1-((5-methoxy-7-((2-(trifluoromethyl)-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (75)
(2S,4R)-4-hydroxy-1-((5-methoxy-7-((2-(trifluoromethyl)-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)pyrrolidine-2-carboxylic acid (76)
(2S)-1-((7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-5-((1-methylpiperidin-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (77)
(S)-1-((5-(4-carboxybutoxy)-7-((2-cyano-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (78)
N-(2-(((5-(4-cyanobutoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (79)
(S)-1-((5-(4-cyanobutoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxamide (80)
(2S,4R)-1-((5-(4-cyanobutoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (81)
(S)-1-((5-(((1S,2R)-2-carboxycyclopropyl)methoxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (82)
(1R,2S)-2-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)cyclopropane-1-carboxylic acid (83)
(S)-1-((7-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (84)
(2S,4R)-1-((7-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methoxy-2,3-dihydro-1H-inden-4-yl)methyl)-4-hydroxypyrrolidine-2-carboxylic acid (85)
N-(2-(((5-((3-cyanobenzyl)oxy)-7-((2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (86)
N-(2-(((5-((3-cyanobenzyl)oxy)-7-((4′-fluoro-2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)amino)ethyl)acetamide (87)
(S)-1-((5-((3-carbamoylbenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)piperidine-2-carboxylic acid (88)
3-(((4-(aminomethyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)benzonitrile (89)
N-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)acetamide (90)
6-acetamido-N-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)hexanamide (91)
3-(((4-((dimethylamino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)benzonitrile (92)
5-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)nicotinic acid (93)
5-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)nicotinamide (94)
3-(((4-(((2-acetamidoethyl)amino)methyl)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-5-yl)oxy)methyl)benzamide (95)
(S)-1-((3-methoxy-1-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-6,7-dihydro-5H-cyclopenta[c]pyridin-4-yl)methyl)piperidine-2-carboxylic acid (96)
N-(2-(((3-methoxy-1-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-6,7-dihydro-5H-cyclopenta[c]pyridin-4-yl)methyl)amino)ethyl)acetamide (97)
(S)-4-((5-methoxy-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)morpholine-3-carboxylic acid (98)
5-((5-((3-cyanobenzyl)oxy)-7-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2,3-dihydro-1H-inden-4-yl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxylic acid (99).

95 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/980,284Filed 13 Mar 2019
Priority: IN 20184100925213 Mar 2018
Published: US 2021/0015810 A121 Jan 2021
Granted: 20 Dec 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification33 codes

A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61P 35/00
Antineoplastic agents
A61K 31/165
Amides, e.g. hydroxamic acids: having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/397
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having four-membered rings, e.g. azetidine

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US 2021/0015810 A1Pre-grant publication · published 21 Jan 2021
US 11,529,341 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula I

their stereoisomers and pharmaceutically acceptable salts thereof,
wherein, X1 is selected from —CH2O— or —OCH2—;
R4 is hydrogen;
X is selected from CR3 or N;
R1, R2, R3, R6, and R7 are independently selected from hydrogen, halo, C1-6 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl-, and C(O)ORa, wherein the C1-6 alkyl and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, are independently optionally substituted with 1, 2, or 3 Rb substituents;
Ra is selected from hydrogen, C1-6 alkyl, C1-4 haloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, or (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein, the C1-6 alkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl- and (4-10 membered heterocycloalkyl)-C1-4 alkyl- are independently optionally substituted with 1, 2, or 3 Rd substituents;
Rb is selected from hydroxy, amino, C1-4 alkyl, 4-10 membered heterocycloalkyl, ORc, C(O)NRcRc, C(O)ORc, NHRc, NRcRc, or NRcC(O)Rc;
wherein, the C1-4 alkyl and 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 Rd substituents;
Rc is selected from hydrogen, C1-6 alkyl, or C3-10 cycloalkyl, wherein, the C1-6 alkyl and C3-10 cycloalkyl are optionally substituted with 1, 2, or 3 Rf substituent;
Rd is selected from cyano, C1-6 alkyl, halo, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C(O)NRcRc, or C(O)ORc, wherein, the C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are optionally substituted with 1, 2, or 3 Rf substituents;
Rf is selected from C1-4 alkyl, halogen, CN, C(O)NRgRg, C(O)ORg, or NRgC(O)Rg;
Rg is selected from hydrogen or C1-6 alkyl;
m is 1 or 2;
Ring A is substituted or unsubstituted C6-10 aryl, substituted with C1-4 alkyl, cyano, or C1-4 haloalkyl;
Ring B is selected from C6-10 aryl, C3-6 cycloalkyl, 5-10 membered monocyclic saturated or unsaturated heterocyclic ring with 1-3 heteroatoms selected from N, S or O.

12 more elements

Facts

Application

16/980,284Filed 13 Mar 2019

Priority

IN 20184100925213 Mar 2018

Published

US 2021/0015810 A121 Jan 2021

Granted

20 Dec 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification33 codes

A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61P 35/00
Antineoplastic agents
A61K 31/165
Amides, e.g. hydroxamic acids: having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/397
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having four-membered rings, e.g. azetidine