Autotaxin inhibitors and uses thereof

摘要

Described herein are compounds that are inhibitors of autotaxin. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such inhibitors, alone and in combination with other compounds, for treating autotaxin-dependent or autotaxin-mediated conditions or diseases.

主权项

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the following structure: wherein, R1 is H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6-fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, or -L1-R4; L1 is substituted or unsubstituted C1-C6alkylene, substituted or unsubstituted phenylene, or substituted or unsubstituted monocyclic heteroarylene; R4 is substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted naphthyl, or substituted or unsubstituted monocyclic heteroaryl; R2 is H, C1-C4alkyl or C1-C4-fluoroalkyl; X is —O—, or —S—, provided that if X is —O—, L2 is not absent, L2 is absent, C1-C6alkylene or C3-C6cycloalkylene; RA is —CO2H, —CO2(C1-C6alkyl), —OH, —CN, —B(OH)2, —C(═O)NHSO2R9, —C(═O)N(R10)2,—C(═O)NHCH2CH2N(CH3)2, —C(═O)NHCH2CH2N(CH3)3, —C(═O)NH—OH, —C(═O)NH-CN, —SO2NHC(═O)R9, —CN, tetrazolyl or carboxylic acid bioisostere; R3 and R5 are each independently H, halogen, —CN, —OH, C1-C4alkyl, C1-C4alkoxy, —S—C1-C4alkyl, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, and C1-C4heteroalkyl; R6 is H, halogen, —CN, —NO2, —OH, —OR9, —SR9, —S(═O)R9, —S(═O)2R9, —S(═O)2N(R10)2, —NR10S(═O)2R9, —C(═O)R9, —OC(═O)R9, —CO2R10, —OCO2R9, —N(R10)2, —C(═O)N(R10)2, —OC(═O)N(R10)2, —NHC(═O)R9, —NHC(═O)OR9, C1-C4alkyl, C1-C4alkoxy, —S—C1-C4alkyl, —S(O)2—C1-C4alkyl, C1-C4-fluoroalkyl, C1-C4-fluoroalkoxy, C1-C4heteroalkyl, C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl; R9 is C1-C6alkyl, C3-C6cycloalkyl, a substituted or unsubstituted phenyl, or a substituted or unsubstituted monocyclic heteroaryl; each R10 is independently selected from H, C1-C6alkyl, C3-C6cycloalkyl, a substituted or unsubstituted phenyl, or a substituted or unsubstituted monocyclic heteroaryl; or two R10 groups attached to the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted heterocycle.