Isoxazole o-linked carbamoyl cyclohexyl acids as LPA antagonists

US11180488B2 · kind B2 · utility

Inventors

• Peter Tai Wah Cheng · Princeton, US
• Robert F. Kaltenbach, III · Wilmington, US
• Hao Zhang · Montgomery, US
• Yan Shi · Flourtown, US
• Jun Li · Foster City, US

Key dates

• Filing date: Dec 18, 2018
• Grant date: Nov 23, 2021
• Expiry date: Dec 18, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D413/12
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; L is C1-4 alkylene substituted with 0 to 4 R7; R1 is (—CH2)aR9; a is an integer of 0 or 1; R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 is hydrogen, C1-6 alkyl, C1-6 deuterated 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; R4 is C1-10 alkyl, C1-10 deuterated alkyl, C1-10 haloalkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, —(C1-6 alkylene)-(C3-8 cycloalkyl), —(C1-6 alkylene)-(6 to 10-membered aryl), —(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or —(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl,…