Pyrazole n-linked carbamoyl cyclohexyl acids as lpa antagonists

Abstract

The present invention provides compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X, X, X, and Xare each independently CRor N; provided that no more than two of X, X, X, or Xare N; Qis N or NR; one of Qand Qis CR, and the other is N or NR; and the dashed circle denotes optional bonds forming an aromatic ring; Yis O or NR; Yis —CO—, —SO—, or —S(O(NH)—; Yis O or NR; provided that (1) Yand Yare not both O, and (2) when Yis C(O), Yis not O; L is a covalent bond or Calkylene substituted with 0 to 4 R; Ris (—CH)R; a is an integer of 0 or 1; Ris each independently halo, cyano, hydroxyl, amino, Calkyl, Ccycloalkyl, Cheterocyclyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxy, alkoxyalkyl, haloalkoxyalkyl, or haloalkoxy; n is an integer of 0, 1, or 2; Rand Rare independently hydrogen, Calkyl, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; Ris Calkyl, Chaloalkyi, Cdeuterated alkyl, Calkenyl, Ccycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, —(Calkylene)—(Ccycloalkyl), —(Calkylene)—(6 to 10-membered aryl), —(Calkylene)—(3 to 8-membered heterocyclyl), or —(Calkylene)—(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R; or alternatively, Rand R, taken together with the N and 0 atoms which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; or alternatively, (Rand R) or (Rand R), taken together with the atoms to which they are attached to, form a 5 to 8-membered heterocyclic ring moiety which is substituted with 0 to 3 R; Ris hydrogen, Calkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; Rand Rare each independently hydrogen, halo, cyano, hydroxyl, amino, alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; Ris halo, oxo, cyano, hydroxyl, amino, Calkyl, Ccycloalkyl, Cheterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; Rare each independently deuterium, halo, hydroxyl, amino, cyano, Calkyl, Cdeuterated alkyl, Calkenyl, Calkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R, taken together with the atom(s) 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; Ris selected from —CN, —C(O)OR, —C(O)NRR—, —CO—NH—CO—R, —CO—NH—SO—R, —CO—NH—SO—R, —SO—OH, —SO—NH—CO—R, —P(O)(OH), tetrazol-5-yl, —CH—CO—NH—CO—R, —CH—CO—NH—SO—R, —CH—CO—NH—SO—R, —CH—SO—OH, —CH—SO—NH—CO—R, —CH—P(O)(OH), tetrazol-5-ylmethylene; Ris Calkyl, Ccycloalkyl, haloalkyl, hydroxyalkyi, aminoalkyi, alkoxyalkyi, or haloalkoxyalkyi; Ris hydrogen or Calkyl; and Rand Rare each independently hydrogen, Calkyl, Ccycloalkyl, Cheterocyclyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, or haloalkoxy; and Ris halo, cyano, hydroxyl, amino, Calkyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.