Isoxazole o-linked carbamoyl cyclohexyl acids as lpa antagonists

Abstract

The present invention provides compounds of Formula (Ia) or (Ib) 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; L is 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, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; Ris hydrogen, Calkyl, Cdeuterated alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy, and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully; Ris Calkyl, Cdeuterated alkyl, Chaloalkyl, 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 atom to which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; Rand Rare each independently hydrogen, halo, cyano, hydroxyl, amino, Calkyl, 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 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; 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, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; Ris hydrogen or Calkyl; and Rand Rare each independently hydrogen, Calkyl, Ccycloalkyl, Cheterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and Ris halo, cyano, hydroxyl, amino, Calkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.