Granted Patent B2

US 12,630,510 · App. 17/621,137 · Granted May 19, 2026

Inventors: Akio Watanabe (Osaka, JP); Atsushi Yoshida (Osaka, JP); Yasuo Hirooka (Osaka, JP); Michael G. Yang (Narberth, PA); Ning Li (Lexington, MA)

Assignee: ONO PHARMACEUTICAL CO., LTD.

C07D207/34A61K31/145A61K31/167A61K31/192A61K31/40A61K31/415A61K31/4174A61K31/44A61K31/4439A61K31/4965A61K31/519A61P35/00C07C233/76C07C323/29C07D213/56C07D213/75C07D231/12C07D233/70C07D241/18C07D401/12C07D487/04C07C2601/16

Abstract

Claims (154)

1 . A compound of formula (I-1):

wherein:

R 38 and R 40 each independently represent (1) a hydrogen atom, (2) a halogen atom, or (3) a C1-4 alkyl group;

the C1-4 alkyl group in each of R 38 and R 40 may be independently substituted by a halogen atom;

L 2 represents (1) a bond, (2) a C1-8 alkylene group, (3) a C2-8 alkenylene group, or (4) a C2-8 alkynylene group, wherein one or two carbon atoms in the C1-8 alkylene group, the C2-8 alkenylene group and the C2-8 alkynylene group may be independently replaced by an oxygen atom or a sulfur atom that may be oxidized, and each of the C1-8 alkylene group, the C2-8 alkenylene group and the C2-8 alkynylene group may be substituted by 1 to 8 halogen atoms;

Y represents (1) a bond, (2) an oxygen atom, or (3) a sulfur atom that may be oxidized;

R 1 represents (1) COOR 10 ;

R 10 represents (1) a hydrogen atom or (2) a C1-4 alkyl group;

R 2 represents (1) a hydrogen atom or (2) a C1-4 alkyl group;

R 3 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) a (3- to 6-membered cyclic group)-O—, or (8) a (3- to 6-membered cyclic group)-(C1-4 alkylene)-;

each of the groups (2) to (8) in R 3 may be substituted by 1 to 9 R 16 s;

when there are a plurality of R 3 s, the plurality of R 3 s may be the same as or different from each other;

R 16 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR 17 R 18 ;

when there are a plurality of R 16 s, the plurality of R 16 s may be the same as or different from each other;

R 17 and R 18 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;

R 4 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) (3- to 6-membered cyclic group)-O—, or (8) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;

each of the groups (2) to (8) in R 4 may be substituted by 1 to 9 R 19 s;

when there are a plurality of R 4 s, the plurality of R 4 s may be the same as or different from each other;

R 19 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR 20 R 21 ;

R 20 and R 21 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;

when there are a plurality of R 19 s, the plurality of R 19 s may be the same as or different from each other;

R 5 represents (1) a hydrogen atom, (2) a C3-10 carbocyclic ring, or (3) a 3- to 10-membered heterocyclic ring, wherein each of the C3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring may be substituted by 1 to 5 R 22 s;

when L 2 represents a bond, R 5 is not a hydrogen atom;

R 22 represents (1) a C1-6 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a C3-6 cycloalkyl group, (5) a C1-6 alkoxy group, (6) a C3-6 cycloalkyloxy group, (7) a C2-6 acyl group, (8) a C2-6 acyloxy group, (9) a C1-6 alkylthio group, (10) a C3-6 cycloalkylthio group, (11) a C1-6 alkylsulfinyl group, (12) a C3-6 cycloalkylsulfinyl group, (13) a C1-6 alkylsulfonyl group, (14) a C3-6 cycloalkylsulfonyl group, (15) a C1-6 alkoxycarbonyl group, (16) a 5- to 6-membered cyclic group, (17) (5- to 6-membered cyclic group)-(C1-4 alkylene)-, (18) a (5- to 6-membered cyclic group)-(C1-4 alkylene)-O— group, (19) a (5- to 6-membered cyclic group)-C1-4 acyl group, (20) a halogen atom, (21) a hydroxyl group, (22) a nitro group, (23) a cyano group, (24) —NR 23 R 24 , (25) —CONR 25 R 26 or (26) —SO 2 NR 27 R 28 ,

R 23 , R 24 , R 25 , R 26 , R 27 and R 28 each independently represent (1) a hydrogen atom, (2) a C1-6 alkyl group, (3) a C2-6 acyl group or (4) a C1-6 alkylsulfonyl group;

each of the groups (1) to (19) in R 22 may be substituted by 1 to 9 R 29 s;

when there are a plurality of R 22 s, the plurality of R 22 s may be the same as or different from each other;

R 29 represents (1) a C1-4 alkyl group, (2) a C1-4 alkoxy group, (3) a C2-6 acyl group, (4) a C3-6 cycloalkyl group, (5) a hydroxyl group, (6) —NR 30 R 31 or (7) a halogen atom;

R 30 and R 31 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;

when there are a plurality of R 29 s, the plurality of R 29 s may be the same as or different from each other;

X represents (1) CR 6 or (2) NR 7 ;

R 6 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) (3- to 6-membered cyclic group)-O—, or (8) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;

each of the groups (2) to (8) in R 6 may be substituted by 1 to 9 R 32 s;

R 32 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR 33 R 34 ;

R 33 and R 34 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;

when there are a plurality of R 32 s, the plurality of R 32 s may be the same as or different from each other;

R 7 represents (1) a C1-6 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a 3- to 6-membered cyclic group, or (5) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;

R 7 may be substituted by 1 to 9 R 35 s;

R 35 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR 36 R 37 ,

R 36 and R 37 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;

when there are a plurality of R 35 s, the plurality of R 35 s may be the same as or different from each other;

the ring A represents (1) a benzene ring, or (2) a 5- to 6-membered nitrogen-containing aromatic heterocyclic ring;

the symbol

in the ring A represents a single bond or a double bond;

n represents an integer of 1 to 4;

m represents an integer of 0 to 3; and

p represents an integer of 1 to 4,

or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-C):

wherein:

X a represents CR 6a or NR 7a ;

R 6a represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) (3- to 6-membered cyclic group)-O—, or (7) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;

each of the groups (2) to (7) in R 6a may be substituted by 1 to 9 R 32 s;

R 7a represents (1) a C1-6 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a 3- to 6-membered cyclic group, or (5) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;

R 7a may be substituted by 1 to 9 R 35 s;

R 3a , R 3b and R 3c each independently represent (1) a hydrogen atom, (2) a halogen atom, (3) a C1-6 alkyl group, (4) a C2-6 alkenyl group, (5) a C2-6 alkynyl group, (6) a C1-6 alkoxy group, (7) a 3- to 6-membered cyclic group, (8) (3- to 6-membered cyclic group)-O—, or (9) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;

each of the groups (3) to (9) in R 3a , R 3b and R 3c may be substituted by 1 to 9 R 16 s;

wherein at least one of R 3a , R 3b and R 3c represents a substituent other than a hydrogen atom;

p represents an integer of 1 to 4; and

the same symbols as those recited in claim 1 have the same meanings as those recited in claim 1 .

3 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the ring A is a benzene ring or a 5-membered nitrogen-containing aromatic heterocyclic ring.

4 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the ring A is a pyrrole ring and Y is a bond.

5 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the ring A is a benzene ring and Y is an oxygen atom.

6 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

(1) rel-(1R,2S)-2-{3-([1-sec-butyl-5-(3-phenylpropyl)-1H-pyrrole-2-carbonyl]amino)-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(2) rel-(1R,2S)-2-{3-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(3) rel-(1R,2S)-2-{3-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-5-methylphenyl}cyclopropanecarboxylic acid;

(4) rel-(1R,2R)-2-{3-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-5-methylphenyl}cyclopropanecarboxylic acid;

(5) rel-(1R,2S)-2-{5-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-2-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(6) rel-(1R,2R)-2-{5-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-2-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(7) (1S,2R)-2-[3-({[1-isopropyl-5-(3-phenylpropyl)-1H-pyrrol-2-yl]carbonyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(8) (1R,2R)-2-[3-({[1-isopropyl-5-(3-phenylpropyl)-1H-pyrrol-2-yl]carbonyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(9) (1R,2S)-2-{3-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-4-methoxyphenyl}cyclopropanecarboxylic acid;

(10) (1S,2R)-2-{3-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(11) (1R,2S)-2-{3-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(12) (1R,2S)-2-{3-[({1-[(2S)-2-butanyl]-5-(3-phenylpropyl)-1H-pyrrol-2-yl}carbonyl)amino]-4-chlorophenyl}cyclopropanecarboxylic acid;

(13) (1R,2S)-2-{3-[({5-[2-(benzyloxy)ethyl]-1-[(2S)-2-butanyl]-1H-pyrrol-2-yl}carbonyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(14) rel-(1R,2S)-2-[3-{[(1-[(2S)-2-butanyl]-5-{2-[(2-fluoro-4-pyridinyl)oxy]ethyl}-1H-pyrrol-2-yl)carbonyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(15) (1R,2S)-2-[3-{[(1-[(2S)-2-butanyl]-5-{2-[(2-chloro-6-fluoro-4-pyridinyl)oxy]ethyl}-1H-pyrrol-2-yl)carbonyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(16) (1R,2S)-2-{3-[({1-[(2S)-2-butanyl]-5-[2-(2-chloro-3,5-difluorophenoxy)ethyl]-1H-pyrrol-2-yl}carbonyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(17) (1R,2S)-2-{3-[({1-[(2S)-2-butanyl]-5-[2-(2,4-difluorophenoxy)ethyl]-1H-pyrrol-2-yl}carbonyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(18) (1R,2S)-2-[3-{[(1-[(2S)-2-butanyl]-5-{2-[(1-methyl-1H-pyrazol-4-yl)oxy]ethyl}-1H-pyrrol-2-yl)carbonyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(19) rel-(1R,2S)-2-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(20) (1R,2S)-2-[3-{[2,6-dimethyl-4-(3-phenylpropyl)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(21) (1R,2S)-2-[3-({4-[2-(2,4-difluorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(22) rel-(1R,2S)-2-(2,3-dichloro-5-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-fluorophenyl)cyclopropanecarboxylic acid;

(23) rel-(1R,2R)-2-(2,3-dichloro-5-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-fluorophenyl)cyclopropanecarboxylic acid;

(24) (1R,2S)-2-[2-chloro-5-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(25) (1R,2S)-2-(4-chloro-3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}phenyl)cyclopropanecarboxylic acid;

(26) rel-(1R,2S)-2-(2,3-dichloro-5-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}phenyl)cyclopropanecarboxylic acid;

(27) rel-(1R,2R)-2-(2,3-dichloro-5-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}phenyl)cyclopropanecarboxylic acid;

(28) (1R,2S)-2-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(29) (1S,2R)-2-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(30) (1R,2S)-2-[3-({2,6-dimethyl-4-[2-(1-methyl-1H-pyrazol-4-yl)ethoxy]benzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(31) (1R,2S)-2-[3-{[4-(2-cyclopropylethoxy)-2,6-dimethylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(32) (1R,2S)-2-{3-[(2,6-dimethyl-4-propoxybenzoyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(33) (1R,2S)-2-[3-{[4-(hexyloxy)-2,6-dimethylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(34) (1R,2S)-2-[3-{[4-(benzyloxy)-2,6-dimethylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(35) (1R,2S)-2-[3-{[4-(2-methoxyethoxy)-2,6-dimethylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(36) (1R,2S)-2-[3-({2,6-dimethyl-4-[2-(tetrahydro-2H-pyran-2-yl)ethoxy]benzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(37) (1R,2S)-2-[3-({4-[2-(2-furyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(38) (1R,2S)-2-[3-({4-[2-(2-chlorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(39) (1R,2S)-2-[3-({4-[2-(3-chlorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(40) (1R,2S)-2-[3-({4-[2-(1H-imidazol-1-yl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(41) (1R,2S)-2-[3-({4-[2-(2,6-difluorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(42) (1R,2S)-2-[3-({4-[2-(3,5-difluorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(43) (1R,2S)-2-[3-({4-[(6-chloro-2-pyrazinyl) oxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(44) (1R,2S)-2-[3-{[4-(6-fluoro-3-pyridinyl)-2,6-dimethylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(45) (1R,2S)-2-[3-({4-[2-(4-hydroxyphenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(46) 3-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl] propanoic acid;

(47) 3-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl] butanoic acid;

(48) 3-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]-2-methylpropanoic acid;

(49) (1R,2S)-2-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclobutanecarboxylic acid; or

(50) (1R,2R)-2-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]-1-methylcyclopropanecarboxylic acid.

7 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

(1) (1R,2S)-2-[3-{[2-methyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(2) (1R,2S)-2-[3-{[2-chloro-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(3) (1R,2S)-2-[3-{[4-(2-phenylethoxy)-2-(trifluoromethyl)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(4) (1R,2S)-2-[3-{[4-(1H-indazol-5-ylmethoxy)-2,6-dimethylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(5) (1R,2S)-2-[3-{[2,6-dimethyl-4-(1,2,3,4-tetrahydro-1-naphthalenylmethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(6) (1R,2S)-2-[3-({2,6-dimethyl-4-[2-(3-pyridinyl)ethoxy]benzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(7) (1R,2S)-2-[3-({2,6-dimethyl-4-[2-(4-pyridinyl)ethoxy]benzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(8) (1R,2S)-2-[3-({2,6-dimethyl-4-[2-(2-pyridinyl)ethoxy]benzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(9) (1R,2S)-2-[3-({4-[2-(2-chloro-1H-imidazol-1-yl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(10) (1R,2S)-2-[3-({4-[2-(2-fluorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(11) (1R,2S)-2-[3-({4-[2-(3-fluorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(12) (1R,2S)-2-[3-({4-[2-(4-fluorophenyl)ethoxy]-2,6-dimethylbenzoyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(13) (1R,2S)-2-[3-{[2,6-dimethyl-4-(3,3,3-trifluoropropoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(14) (1R,2S)-2-[3-{[2,6-dimethyl-4-(3,3,3-trifluoro-2-methylpropoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(15) (1R,2S)-2-{3-[(2,6-dimethyl-4-{[6-(trifluoromethyl)-2-pyridinyl]oxy}benzoyl)amino]-4-(trifluoromethyl)phenyl}cyclopropanecarboxylic acid;

(16) (1R,2S)-2-[3-{[2,6-dimethyl-4-(pyrazolo[1,5-a]pyrimidin-5-yloxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(17) rel-(1R,2S)-2-(3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-methylphenyl)cyclopropanecarboxylic acid;

(18) (1R,2S)-2-[3-{[4-(benzyloxy)-2-isopropylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(19) (1R,2S)-2-[3-{[2-isopropyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(20) (1R,2S)-2-[3-{[2-isopropyl-4-(3-phenylpropoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(21) (1R,2S)-2-[3-{[3-(benzyloxy)-2-isopropylbenzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(22) (1R,2S)-2-[3-{[2-isopropyl-3-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(23) (1R,2S)-2-[3-{[2-isopropyl-3-(3-phenylpropoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(24) (1R,2S)-2-[4-(trifluoromethyl)-3-{[2,3,5-trimethyl-4-(2-phenylethoxy)benzoyl]amino}phenyl]cyclopropanecarboxylic acid;

(25) (1R,2S)-2-[3-({[3-isopropyl-1-(3-phenylpropyl)-1H-pyrazol-4-yl]carbonyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(26) (1R,2S)-2-[3-({[5-isopropyl-1-(3-phenylpropyl)-1H-pyrazol-4-yl]carbonyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(27) (1R,2S)-2-[3-({[2,6-dimethyl-4-(2-phenylethoxy)phenyl]carbonothioyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(28) (1R,2S)-2-[3-({[4-(2-cyclopropylethoxy)-2,6-dimethylphenyl]carbonothioyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(29) (1R,2S)-2-[3-({[2-sec-butyl-1-(3-phenylpropyl)-1H-pyrrol-3-yl]carbonyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid;

(30) (1R,2S)-2-[3-({[2-isopropyl-1-(3-phenylpropyl)-1H-pyrrol-3-yl]carbonyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid; or

(31) (1R,2S)-2-[3-({[2-(2-methyl-2-propanyl)-1-(3-phenylpropyl)-1H-pyrrol-3-yl]carbonyl}amino)-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid.

8 . A pharmaceutical composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier.

9 . The pharmaceutical composition according to claim 8 , wherein the pharmaceutical composition is an EP 2 receptor antagonist.

10 . A treatment regimen, comprising the pharmaceutical composition according to claim 8 , and

at least one component selected from an alkylating agent, an antimetabolic agent, an anticancer antibiotic, a plant-derived preparation, a hormonal agent, a platinum compound, a topoisomerase inhibitor, a kinase inhibitor, an anti-CD20 antibody, an anti-human epidermal growth factor receptor (HER2) antibody, an anti-epidermal growth factor receptor (EGFR) antibody, an anti-vascular endothelial growth factor (VEGF) antibody, a proteasome inhibitor, a histone deacetylase (HDAC) inhibitor and an immunomodulatory drug.

11 . A method for treating colorectal cancer in a patient in need thereof, the method comprising administering the compound according to claim 1 , or a pharmaceutically acceptable salt thereof to the patient.

12 . A compound or a pharmaceutically acceptable salt thereof, wherein the compound is (1R,2S)-2-[3-{[2,6-dimethyl-4-(2-phenylethoxy)benzoyl]amino}-4-(trifluoromethyl)phenyl]cyclopropanecarboxylic acid.

13 . A compound of the following structure:

14 . A pharmaceutically acceptable salt of the compound of the following structure:

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (22)