Triazole N-linked carbamoyl cyclohexyl acids as LPA antagonists
The present invention provides compounds of Formula (I): or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.
1. A compound according to Formula (I):
or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein:
X 1 , X 2 , X 3 , and X 4 are each independently CR 6 or N; provided that no more than two of X 1 , X 2 , X 3 , or X 4 are N;
one of Q 1 , Q 2 , and Q 3 is NR 5 , and the other two are N; and the dashed circle denotes optional bonds forming an aromatic ring;
Y 1 is O or NR 3 ;
Y 2 is
Y 3 is O or NR 4a ; provided that (1) Y 1 and Y 3 are not both O, and (2) when Y 2 is C(O), Y 1 is not O;
L is a covalent bond or C 1-4 alkylene substituted with 0 to 4 R 7 ;
R 1 is (—CH 2 ) a R 9 ;
a is an integer of 0 or 1;
R 2 is each independently halo, cyano, hydroxyl, amino, C 1-6 alkyl, C 3-6 cycloalkyl, C 4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyalkyl, or haloalkoxy;
n is an integer of 0, 1, or 2;
R 3 and R 4a are each independently hydrogen, C 1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R 4 is C 1-10 alkyl, C 1-10 deuterated alkyl, C 1-10 haloalkyl, C 1-10 alkenyl, C 3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, —(C 1-6 alkylene)-(C 3-8 cycloalkyl), —(C 1-6 alkylene)-(6 to 10-membered aryl), —(C 1-6 alkylene)-(3 to 8-membered heterocyclyl), or —(C 1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R 8 ; or alternatively, R 3 and R 4 taken together with the atoms to which they are attached, form a 4- to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R 8 ;
R 5 is hydrogen, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R 6 is hydrogen, halo, cyano, hydroxyl, amino, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R 7 is halo, oxo, cyano, hydroxyl, amino, C 1-6 alkyl, C 3-6 cycloalkyl, C 4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R 8 are each independently deuterium, halo, hydroxyl, amino, cyano, C 1-6 alkyl, C 1-6 deuterated alkyl, C 2-6 alkenyl, C 2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, —CHO, phenyl, or 5 to 6 membered heteroaryl; or alternatively, two R 8 , taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R 12 ;
R 9 is selected from —CN, —C(O)OR 10 , —C(O)NR 11a R 11b ,
R e is C 1-6 alkyl, C 3-6 cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl;
R 10 is hydrogen or C 1-10 alkyl;
R 11a and R 11b are each independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and
R 12 is halo, cyano, hydroxyl, amino, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6 membered heteroaryl.
2. The compound according to claim 1 , wherein
the
moiety is
3. The compound according to claim 2 , wherein
the
moiety is selected from
Y 4 is O or NH.
4. The compound according to claim 3 , wherein n is 0 or 1.
5. The compound according to claim 4 , wherein R 5 is C 1-4 alkyl.
6. The compound according to claim 5 , wherein R 1 is CO 2 H.
7. The compound according to claim 6 , wherein
R 3 and R 4 , taken together with the N and O to which they are attached, form a 5 to 7-membered heterocyclic ring moiety which is substituted with 1 R 8 ; and
R 8 is benzyl or phenyl.
8. The compound according to claim 1 , wherein
R 4 is C 1-10 alkyl, C 1-10 haloalkyl, C 3-6 cycloalkyl, —(C 1-4 alkylene)-(C 3-6 cycloalkyl), —(C 1-4 alkylene)-(C 1-6 alkoxy), or —(C 1-4 alkylene)-phenyl; wherein each of the alkyl, alkylene, cycloalkyl, and phenyl, by itself or as part of another group, is independently substituted with 0 to 3 R 8 ; and
R 8 is each independently halo, hydroxyl, amino, cyano, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; or alternatively, two R 8 , taken together with the atom(s) to which they are attached, form a 3 to 6-membered carbocyclic ring.
9. The compound according to claim 1 , which is represented by Formula (IIa), (IIb), (IIc), (IId), (IIe), or (IIf):
or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein:
each R 7a is independently hydrogen, halo, oxo, cyano, hydroxyl, amino, C 1-6 alkyl, C 3-6 cycloalkyl, C 4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
f is an integer of 0, 1, or 2;
R 3 and R 4a are each independently hydrogen or C 1-4 alkyl;
R 4 is C 1-10 alkyl, C 3-8 cycloalkyl, 6 to 10-membered aryl, —(C 1-6 alkylene)-(C 3-8 cycloalkyl), or —(C 1-6 alkylene)-(6 to 10-membered aryl); wherein each of the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R 8 ; or alternatively, R 3 and R 4 , taken together with the N and O to which they are attached, form a 4- to 6-membered heterocyclic ring moiety which is substituted with 0 to 3 R 8 ;
n is 0 or 1; and
R 1 , R 2 , R 5 , R 5a , R 8 ; X 1 , X 2 , X 3 , X 4 , and Z are the same as defined in any one of claims 1 to 7 .
10. The compound according to claim 9 , wherein X 1 is CR 6 , where R 6 is hydrogen, C 1-4 alkyl, C 1-4 haloalkyl, or C 1-4 alkoxyalkyl.
11. The compound according to claim 9 , wherein X 3 is N.
12. The compound according to claim 9 , wherein
the
moiety is selected from
R 6a is each independently halo, cyano, hydroxyl, amino, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and
d is an integer of 0, 1, or 2.
13. The compound according to claim 12 , wherein
the
moiety is selected from the from
R 6 is each independently hydrogen, halo, cyano, hydroxyl, amino, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy.
14. The compound according to claim 9 , wherein f is 0 or 1.
15. The compound according to claim 1 , which is represented by Formula (IIIa) or (IIIb):
or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein:
R 2a is hydrogen, chloro, fluoro, or C 1-4 alkyl;
R 3 is hydrogen or C 1-6 alkyl; and
R 1 , R 4 , X 1 , X 2 , X 3 , and X 4 are the same as defined in any one of claims 1 to 14 .
16. The compound according to claim 15 , wherein the
moiety is selected from
17. The compound according to claim 15 , wherein R 1 is CO 2 H.
18. The compound according to claim 15 , wherein
the
moiety is selected from
R 6 is each independently hydrogen, CH 3 , CH 2 CH 3 , CH 2 OCH 3 , CHF 2 , or CF 3 .
19. The compound according to claim 15 , wherein
R 4 is C 3-10 alkyl, C 3-10 haloalkyl, C 3-6 cycloalkyl, phenyl, —(C 1-4 alkylene)-(C 1-3 alkoxy), —(C 1-4 alkylene)-(C 3-6 cycloalkyl), or benzyl; wherein the alkyl, alkylene, cycloalkyl, and benzyl are each independently substituted with 0 to 3 R 8 ; and
R 8 is each independently halo, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; or alternatively, two R 8 , taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring.
20. The compound according to claim 15 , wherein
R 4 is C 3-10 alkyl, C 3-10 haloalkyl, cyclobutyl, cyclopentyl, —(CH 2 ) 1-2 —(C 1-3 alkoxy), —(CHR 8a ) 1-2 -cyclopropyl, —(CHR 8a ) 1-2 -cyclobutyl, or —(CHR 8a ) 1-2 -phenyl; wherein the cyclopropyl, cyclobutyl, cyclopentyl, and phenyl are each independently substituted with 0 to 3 R 8 ; or alternatively, two R 8 , taken together with the atom to which they are attached, form cyclopropyl;
R 8a is each independently hydrogen or methyl; and
R 8 is each independently halo or C 1-4 alkyl.
21. The compound according to claim 15 , which is represented by Formula (VI):
or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein:
R 2a is hydrogen, chloro, fluoro, or C 1-4 alkyl;
R 3 is hydrogen or C 1-6 alkyl;
R 4 is C 1-10 alkyl, —(C 1-6 alkylene) 0-1 -phenyl, or —(C 1-6 alkylene) 0-1 -(C 3-8 cycloalkyl);
and
R 6 is hydrogen, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy.
22. The compound according to claim 21 , wherein:
R 4 is C 1-6 alkyl, —(CH 2 ) 0-2 —(C 3-6 cycloalkyl), —(CHCH 3 )—(C 3-6 cycloalkyl), —(CH 2 ) 1-2 -phenyl, or —(CHCH 3 )-phenyl and
R 6 is methyl or ethyl.
23. The compound according to claim 1 , which is selected from:
(1S,3S)-3-((2-Methyl-6-(1-methyl-5-(((((S)-2-methylbutoxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((2-Methyl-6-(1-methyl-5-((methyl(((S)-2-methylbutoxy)carbonyl)amino) methyl)-1H-1,2,3-triazol-4-yl)pyridine-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((6-(5-(((butoxycarbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(±)-(trans)-3-(4-(5-((((isopentyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)phenoxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((butoxycarbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((cyclopentyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((cyclopropyl-methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((3,5-difluoro-benzyl)oxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-(((phen-ethoxycarbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridine-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-(((((R)-1-phenylethoxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl) pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((3-fluoro-benzyl)oxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((3-fluorobenzyl)oxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((hexyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((butoxycarbonyl)(methyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy) cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-((methyl ((pentyloxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((phenethoxycarbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((2,5-difluoro-benzyl)oxy)carbonyl)amino)methyl)-1-methyl-H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((R)-1-phenylethoxy)carbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((3-methylbenzyl)oxy)carbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((hexyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((2-methoxy-ethoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((neopentyloxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((pentyloxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((propoxycarbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((isobutoxy-carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-((((neo-pentyloxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carb oxylic acid,
(1S,3S)-3-((6-(1-methyl-5-((((pentyloxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carb oxylic acid,
(1S,3S)-3-((6-(5-((((cyclopentyl-oxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((isobutoxy-carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((tert-butoxycarbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-((((4,4,4-trifluoro-2-methylbutoxy)carbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((4,4,4-trifluoro-2-methylbutoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclo-hexane- 1-carboxylic acid,
(1S,3S)-3-((6-(5-((((cyclobutyl-methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxyli c acid,
(1S,3S)-3-((6-(5-((((benzyloxy)carbonyl)(methyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((6-(5-(((butoxycarbonyl)(methyl)amino) methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane carboxylic acid,
(1S,3S)-3-((6-(5-((((3,3-dimethyl-butoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((6-(5-(((((3,3-dimethylcyclobutyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylic acid,
(±)-trans-3-(4-(5-((((2-cyclopropyl-ethoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)phenoxy)cyclohexane-1-carboxylic acid,
(±)-trans-3-(4-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)phenoxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((butoxycarbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-ethyl-6-(1-methyl-5-(((propoxycarbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((cyclopentyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethylpyridin-3-yl)oxy)cyclo-hexane-1-carboxylic acid,
(1S,3S)-3-((2-ethyl-6-(1-methyl-5-((((neopentyloxy)carbonyl)amino)methyl)-1H-H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-ethyl-6-(5-(((isobutoxy-carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((3-fluorocyclobutyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((3-fluorocyclobutyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((1-fluorocyclopropyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-(((((1-propylcyclopropyl)methoxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((1-ethylcyclopropyl)methoxy)carbonyl)amino) methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-(((((1-methylcyclopropyl)methoxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((3-methoxy-propoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((1-propylcyclobutyl)methoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((3-fluoropropoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((2-ethoxyethoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((1-ethylcyclobutyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((1-ethylcyclo-propyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((1-methylcyclopropyl)methoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((1-propylcyclopropyl) methoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyri din-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-3-methylpyrazin-2-yl)oxy)cyclohexane-I-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((p-tolyloxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyri dine-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((4-methoxy-phenoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl pyridin-3-yl)oxy)cyclo-hexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((tert-butoxycarbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((3,3-dimethyl-butoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclopentyloxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((neopentyl oxy)carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((propoxycarbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((1-cyclopropyl-ethoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((isopropoxycarbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((pentyloxy)carbonyl)amino)-1H-H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((R)-1-phenylethoxy)carbonyl) amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((2-cyclopropyl-ethoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclopropyl-methoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclobutyl-methoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclohexyl-methoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((isopentyloxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((isobutoxy-carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclopentylmethoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((benzyloxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclobutyl-methoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((R)-1-cyclopropyl-ethoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclopropyl-methoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((2-cyclopropyl-ethoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((isopentyloxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclohexyl-methoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((isobutoxy-carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-(((pentyl-oxy)carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((butoxycarbonyl) amino)-i-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-I-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclopentyloxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-((((R)-1-phenylethoxy)carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy) cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((benzyl oxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(trifluoro-methyl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((isobutoxy-carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(trifluoro-methyl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((butoxycarbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(trifluoromethyl) pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-(((propoxy-carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)-2-(trifluoromethyl) pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
1S,3S)-3-((6-(5-((((cyclopentyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(trifluoro-methyl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((4-fluorobutoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(trifluoro-methyl)pyridine-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(difluoro-methyl)pyridine-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-(difluoromethyl)-6-(5-(((isobutoxycarbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl) pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((butoxycarbonyl) amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(difluoromethyl) pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-(difluoromethyl)-6-(1-methyl-5-(((propoxycarbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-(methoxy-methyl)pyridin-3-yl)oxy)cyclohexane-I-carboxylic acid,
(1S,3S)-3-((6-(5-(2-((((2-chloro-benzyl)oxy)carbonyl)amino)ethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(2-(((neopentyloxy)carbonyl)amino)ethyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(2-(((cyclopentyl-oxy)carbonyl)amino)ethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(2-(((benzyloxy)carbonyl)amino)ethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(2-((butoxy-carbonyl)amino)ethyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-(cyclobutylmethyl)-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((6-(5-((3-benzyl-3-methyl-ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-methyl-3-propylureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-methyl-3-pentylureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((6-(5-((3-benzylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-benzyl-1-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-(2-cyclopropyl-ethyl)-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-benzyl-1,3-dimethylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-isopentyl-3-methyl-ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-(bicyclo [2.2.1] heptan-2-yl)ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-(2-methylbutyl)ureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-(1-phenylbutyl)ureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-(1-phenylpropyl)ureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-(2-fluoro-1-phenyl-ethyl)ureido)methyl)-i-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-isopentyl-ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-((3,3-difluorocyclo-butyl)methyl)ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-butylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-methyl-3-(3-methylbutan-2-yl)ureido) methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-(3-methylbutan-2-yl)ureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-isobutylureido) methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-isobutyl-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(I-methyl-5-((3-(1-phenylethyl)ureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclo-hexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-((R)-1-phenylethyl)ureido) methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-methyl-3-((R)-1-phenylethyl)ureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((3-methyl-3-((S)-1-phenylethyl) ureido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-(tert-butyl)-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-isopropyl-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-I-carboxylic acid,
(1S,3S)-3-((6-(5-(3-benzylureido)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(3-((R)-1-phenylethyl)ureido)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((N-(cyclopentylmethyl)-N-methylsulfamoyl)amino)methyl)-1-methyl-H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((N-butyl-N-methylsulfamoyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((N-benzyl-N-methylsulfamoyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((pentan-2-yloxy)carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclohexyloxy)carbonyl)amino)-1-methyl-H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((pentan-3-yl oxy)carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((2-fluoropropoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((3-fluoropropoxy)carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((3,3,3-trifluoropropoxy)carbonyl) amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(3-((R)-1-cyclopropylethyl)ureido)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(3-(pentan-2-yl)ureido)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-(cyclobutyl methyl)-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-benzyl-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-butyl-3-methylureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-butyl-ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-(cyclopropylmethyl)ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((3-benzyl-ureido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-(1-methyl-5-((((4,4,4-trifluoro-2-methylbutoxy)carbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyrimidin-5-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((3-methyl-5-(1-methyl-5-((((4,4,4-trifluoro-2-methylbutoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyrazin-2-yl)oxy) cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-(5-((((cyclobutyl-methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-3-methylpyrazin-2-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((2-cyclopropyl-ethoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-(5-((((3,3-dimethyl-butoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-3-methylpyrazin-2-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-(5-(((((3-fluorobenzyl)oxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-3-methylpyrazin-2-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-(5-((((2-cyclopropylethoxy)carbonyl)amino)methyl)-methyl-1H-1,2,3-triazol-4-yl)-3-methylpyrazin-2-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((3-methyl-5-(1-methyl-5-(((((S)-2-methylbutoxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyrazin-2-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((4-fluorobutoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((1-(2-fluoro-ethyl)cyclopropyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((2,2-dimethyl-cyclopropyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl) oxy) cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((((S)-pentan-2-yl)oxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((5,5,5-trifluoropentyl)oxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((R)-1-cyclo-propylethoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((3,3-dimethyl-cyclobutoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((4,4,4-trifluorobutoxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((((R)-3-methylbutan-2-yl)oxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((((R)-pentan-2-yl)oxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((R)-sec-butoxy carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((((S)-3-methylbutan-2-yl)oxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((((S)-1,1,1-trifluoropropan-2-yl) oxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyri din-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((S)-sec-butoxy-carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((S)-1-cyclo-propylethoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((cyclobutoxy carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((3,3-difluoro-cyclobutoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((2-methylcyclopropyl)methoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((2,2-difluoro-cyclopropyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((3,3,3-trifluoropropoxy)carbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((3,3-difluoro-cyclobutyl)methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((trans-2-methylcyclopropyl)methoxy)carbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((2-cyclopropyl propoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((2-(1-methylcyclopropyl) ethoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((4,4-difluoro-2-methylbutoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((isopentyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((2,2,3,3,3-pentafluoropropoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((((4-oxopentyl)oxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((2,2-difluoropropoxy)carbonyl)amino)methy)-1-methyl-H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((spiro[2.3]hexan-5-yloxy)carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-I-carboxylic acid,
(1S,3S)-3-((6-(5-((((3,3-difluoro butoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((isobutoxy-carbonyl)(methyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((3,3,3-trifluoro-2-methylpropoxy) carbonyl)amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy) cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((cyclopropyl methoxy)carbonyl)(methyl) amino) methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((4,4-difluoropentyl)oxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((((R)-2,2-difluorocyclopropyl)methoxy)carbonyl)amino) methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(±)-Cis-3-((6-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)-1-fluorocyclohexanecarboxylic acid,
(1R,3 S)-3-((6-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)-1-fluorocyclohexane-1-carboxylic acid,
(1S,3R)-3-((6-(5-((((benzyloxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)-1-fluorocyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((((cyclobutyl methoxy)carbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-5-fluoro-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-fluoro-6-(5-(((isobu-toxycarbonyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-fluoro-2-methyl-6-(1-methyl-5-((((spiro[2.3]hexan-5-yloxy)carbonyl)amino) methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-fluoro-2-methyl-6-(1-methyl-5-(((((1-methylcyclopropyl) methoxy)carbonyl) amino)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((((1-ethylcyclo-propyl)methoxy)carbonyl)amino) methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-5-fluoro-2-methylpyridin-3-yl) oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-[(6-{5-[(butoxycarbonyl) amino]-1-methyl-1H-1,2,3-triazol-4-yl}-5-fluoro-2-methylpyridin-3-yl)oxy]cyclohexane-1-carboxylic acid,
(1S,3S)-3-{[6-(5-{[(cyclopropyl methoxy)carbonyl]amino}-1-methyl-1H-1,2,3-triazol-4-yl)-5-fluoro-2-methylpyridin-3-yl]oxy} cyclohexane-1-carboxylic acid,
(1S,3S)-3-((5-fluoro-6-(5-((isobutoxycarbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((isopropoxy-carbonyl)amino)-1-methyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(1-methyl-5-((pro-poxy-carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((butoxycarbonyl) amino)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((2-methylcyclopropyl)methoxy) carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((((1-methylcyclopropyl)methoxy) carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(((spiro[2.3]hexan-5-yloxy) carbonyl)amino)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((N-(cyclopentyl methyl)sulfamoyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((N-benzyl-sulfamoyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methyl-pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((N-benzyl-N-methyl-sulfamoyl)(methyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-(((N-butyl-N-methyl-sulfamoyl)(methyl)amino)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-{[2-ethyl-6-(1-methyl-5-{[(2-methylpropoxy)carbonyl]amino}-1H-1,2,3-triazol-4-yl) pyridin-3-yl]oxy} cyclohexane-1-carboxylic acid,
(1S,3S)-3-{[6-(5-{[(cyclopropyl-methoxy)carbonyl]amino}-1-methyl-1H-1,2,3-triazol-4-yl)-2-ethylpyridin-3-yl]oxy} cyclohexane-1-carboxylic acid,
(1S,3S)-3-[(6-{5-[(butoxycarbonyl) amino]-1-methyl-1H-1,2,3-triazol-4-yl}-2-ethylpyridin-3-yl)oxy]cyclohexane-1-carboxylic acid,
(1S,3S)-3-[(2-ethyl-6-{1-methyl-5-[(propoxycarbonyl)amino]-1H-1,2,3-triazol-4-yl}pyridin-3-yl)oxy]cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-((2-methyl-2-phenoxypropanamido)methyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((6-(5-((2-cyclopentylacetamido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)-2-methylpyridin-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((6-(5-((2-cyclopentyl acetamido)methyl)-1-methyl-1H-1,2,3-triazol-4-yl)pyridine-3-yl)oxy)cyclohexanecarboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(pentanamidomethyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclo-hexanecarboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(2-(2-phenylacetamido)ethyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid,
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(2-(3,5,5-trimethylhexanamido) ethyl)-1H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid, and
(1S,3S)-3-((2-methyl-6-(1-methyl-5-(2-(4-methylpentanamido)ethyl)-1H-H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)cyclohexane-1-carboxylic acid;
or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof.
24. A pharmaceutical composition comprising one or more compounds according to claim 1 , or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof; and a pharmaceutically acceptable carrier or diluent.
25. A method of treating a disease, disorder, or condition associated with dysregulation of lysophosphatidic acid receptor 1 (LPA 1) in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 1 , or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, to the patient.
26. The method according to claim 25 , wherein the disease, disorder, or condition is pathological fibrosis, transplant rejection, cancer, osteoporosis, or inflammatory disorders.
27. The method according to claim 26 , wherein the pathological fibrosis is pulmonary, liver, renal, cardiac, dernal, ocular, or pancreatic fibrosis.
28. The method according to claim 25 , wherein the disease, disorder, or condition is idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis.
29. The method according to claim 26 , wherein the cancer is of the bladder, blood, bone, brain, breast, central nervous system, cervix, colon, endometrium, esophagus, gall bladder, genitalia, genitourinary tract, head, kidney, larynx, liver, lung, muscle tissue, neck, oral or nasal mucosa, ovary, pancreas, prostate, skin, spleen, small intestine, large intestine, stomach, testicle, or thyroid.
30. A method of treating fibrosis in a mammal having fibrosis, comprising administering a therapeutically effective amount of a compound according to claim 1 , or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, to the mammal.
31. The method according to claim 30 , wherein the fibrosis is idiopathic pulmonary fibrosis (IPF), nonalcoholic steatohepatitis (NASH), chronic kidney disease, diabetic kidney disease, and systemic sclerosis.
32. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 1 , or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, to the mammal.
33. A compound selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
34. A compound selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
35. The compound according to claim 33 , wherein said compound is selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
36. The compound according to claim 33 , wherein said compound is selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
37. The compound according to claim 36 , wherein said compound is selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
38. A compound selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
39. The compound according to claim 38 , wherein said compound is selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
40. A compound selected from:
or a stereoisomer, a pharmaceutically acceptable salt or a solvate thereof.
41. A compound of the formula:
or a stereoisomer or a pharmaceutically acceptable salt thereof.
42. A compound of the formula:
43. A compound of the formula:
or a stereoisomer or a pharmaceutically acceptable salt thereof.
44. A compound of the formula:
45. A compound of the formula:
or a stereoisomer or a pharmaceutically acceptable salt thereof.
46. A compound of the formula:
47. A compound of the formula:
or a stereoisomer or a pharmaceutically acceptable salt thereof.
48. A compound of the formula:
49. A compound of the formula:
or a stereoisomer or a pharmaceutically acceptable salt thereof.
50. A compound of the formula:
51. A compound of the formula:
or a stereoisomer or a pharmaceutically acceptable salt thereof.
52. A compound of the formula:
53. The compound of claim 41 , wherein the stereoisomer is an enantiomer or a diastereoisomer.
54. The compound of claim 43 , wherein the stereoisomer is an enantiomer or a diastereoisomer.
55. The compound of claim 45 , wherein the stereoisomer is an enantiomer or a diastereoisomer.
56. The compound of claim 47 , wherein the stereoisomer is an enantiomer or a diastereoisomer.
57. The compound of claim 49 , wherein the stereoisomer is an enantiomer or a diastereoisomer.
58. The compound of claim 51 , wherein the stereoisomer is an enantiomer or a diastereoisomer.
59. A pharmaceutical composition comprising a compound according to claim 33 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
60. A pharmaceutical composition comprising a compound according to claim 34 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
61. A pharmaceutical composition comprising a compound according to claim 35 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
62. A pharmaceutical composition comprising a compound according to claim 36 , or a stereoisomer or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
63. A pharmaceutical composition comprising a compound according to claim 37 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
64. A pharmaceutical composition comprising a compound according to claim 38 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
65. A pharmaceutical composition comprising a compound according to claim 39 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
66. A pharmaceutical composition comprising a compound according to claim 40 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
67. A pharmaceutical composition comprising a compound according to claim 41 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
68. A pharmaceutical composition comprising a compound according to claim 43 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
69. A pharmaceutical composition comprising a compound according to claim 45 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
70. A pharmaceutical composition comprising a compound according to claim 47 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
71. A pharmaceutical composition comprising a compound according to claim 49 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
72. A pharmaceutical composition comprising a compound according to claim 51 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
73. A pharmaceutical composition comprising the compound according to claim 42 , and one or more pharmaceutically acceptable excipients.
74. A pharmaceutical composition comprising the compound according to claim 44 , and one or more pharmaceutically acceptable excipients.
75. A pharmaceutical composition comprising the compound according to claim 46 , and one or more pharmaceutically acceptable excipients.
76. A pharmaceutical composition comprising the compound according to claim 48 , and one or more pharmaceutically acceptable excipients.
77. A pharmaceutical composition comprising the compound according to claim 50 , and one or more pharmaceutically acceptable excipients.
78. A pharmaceutical composition comprising the compound according to claim 52 , and one or more pharmaceutically acceptable excipients.
79. A method of treating a disease, disorder, or condition associated with dysregulation of lysophosphatidic acid receptor 1 (LPA1) in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 33 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
80. The method according to claim 79 , wherein the disease, disorder, or condition is pathological fibrosis, transplant rejection, cancer, osteoporosis, or inflammatory disorders.
81. The method according to claim 80 , wherein the pathological fibrosis is pulmonary, liver, renal, cardiac, dernal, ocular, or pancreatic fibrosis.
82. The method according to claim 79 , wherein the disease, disorder, or condition is idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis.
83. The method according to claim 80 , wherein the cancer is of the bladder, blood, bone, brain, breast, central nervous system, cervix, colon, endometrium, esophagus, gall bladder, genitalia, genitourinary tract, head, kidney, larynx, liver, lung, muscle tissue, neck, oral or nasal mucosa, ovary, pancreas, prostate, skin, spleen, small intestine, large intestine, stomach, testicle, or thyroid.
84. A method of treating fibrosis in a mammal having fibrosis, comprising administering a therapeutically effective amount of a compound according to claim 33 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
85. The method according to claim 84 , wherein the fibrosis is idiopathic pulmonary fibrosis (IPF), nonalcoholic steatohepatitis (NASH), chronic kidney disease, diabetic kidney disease, and systemic sclerosis.
86. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 33 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
87. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 34 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
88. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 34 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
89. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 35 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
90. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 35 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
91. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 38 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
92. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 38 , or a stereoisomer, or a pharmaceutically acceptable salt or solvate thereof, to the mammal.
93. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 40 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
94. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 40 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
95. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 41 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
96. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 41 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
97. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 42 to the patient.
98. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 42 to the mammal.
99. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 43 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
100. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 43 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
101. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 44 to the patient.
102. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 44 to the mammal.
103. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 45 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
104. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 45 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
105. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 46 to the patient.
106. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 46 to the mammal.
107. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 47 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
108. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 47 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
109. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 48 to the patient.
110. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 48 to the mammal.
111. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 49 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
112. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 49 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
113. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 50 to the patient.
114. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 50 to the mammal.
115. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 51 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
116. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 51 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.
117. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 52 to the patient.
118. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 52 to the mammal.
119. A pharmaceutical composition comprising a compound according to claim 23 , or a stereoisomer or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients.
120. A method of treating a disease, disorder, or condition selected from: idiopathic pulmonary fibrosis (IPF), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, and systemic sclerosis, in a patient having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 23 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the patient.
121. A method of treating a disease, disorder, or condition selected from: lung fibrosis (idiopathic pulmonary fibrosis), asthma, chronic obstructive pulmonary disease (COPD), renal fibrosis, acute kidney injury, chronic kidney disease, liver fibrosis (non-alcoholic steatohepatitis), skin fibrosis, fibrosis of the gut, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, glioblastoma, bone cancer, colon cancer, bowel cancer, head and neck cancer, melanoma, multiple myeloma, chronic lymphocytic leukemia, cancer pain, tumor metastasis, transplant organ rejection, scleroderma, ocular fibrosis, age related macular degeneration (AMD), diabetic retinopathy, collagen vascular disease, atherosclerosis, Raynaud's phenomenon, or neuropathic pain in a mammal having the disease, disorder, or condition, comprising administering a therapeutically effective amount of a compound according to claim 23 , or a stereoisomer, a pharmaceutically acceptable salt or solvate thereof, to the mammal.