POLYCYCLIC COMPOUNDS AS LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS

摘要

Described herein are compounds that are antagonists of lysophosphatidic receptor(s). Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists, alone and in combination with other compounds, for treating LPA-dependent or LPA-mediated conditions or diseases.

主权项

1. A compound having the structure of Formula (I), or a pharmaceutically acceptable salt thereof:wherein,
R1 is —CO2RD, —C(═O)NHSO2RE, —C(═O)N(RD)2, —CN, or tetrazolyl; RD is H or C1-C6 alkyl; RE is C1-C6 alkyl or a substituted or unsubstituted phenyl; L2 is absent, —C(═O)—, —N(RD)—, substituted or unsubstituted C1-C4 alkylene, or substituted or unsubstituted C1-C4heteroalkylene, where if L2 is substituted, then L2 is substituted with R12, where R12 is F, C1-C4alkyl, —OH, or —ORD; ring A is a substituted or unsubstituted phenyl, or a substituted or unsubstituted monocyclic C1-C5heteroarylene excluding [1,2,3]-triazolyl, where if ring A is substituted, then ring A is substituted with 1 or 2 R14, each R14 is independently selected from halogen, —CN, —OH, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4alkoxy, and C1-C4heteroalkyl; L4 is absent, or a substituted or unsubstituted C1-C4 alkylene, where if L4 is substituted then L4 is substituted with R13, where R13 is F, C1-C4alkyl, —OH, or —ORD; R5 is H or C1-C4 alkyl; each RA is independently selected from halogen, —CN, —OH, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4alkoxy, and C1-C4heteroalkyl; each RB is independently selected from halogen, —CN, —OH, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4alkoxy, and C1-C4heteroalkyl; each RC is independently selected from halogen, —CN, —OH, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4alkoxy, and C1-C4heteroalkyl; m is 0, 1 or 2; n is 0, 1 or 2; p is 0, 1 or 2; r is 1, 2, 3, or 4.