Bicyclic sulfonamide compounds as sodium channel inhibitors

摘要

The present invention provides compounds of Formula I,;
and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

主权项

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein: wherein each Ra is independently H, halo, —OH, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —CN, and R1 is a 5 to 10 membered aryl or heteroaryl, wherein the heteroaryl group can have from 1 to 3 heteroatoms independently selected from O, N or S, and the aryl or heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —OC1-6alkylCF3, —OC1-6alkylCN, —C1-6alkylOC1-6alkyl, —(SO2)C1-6alkyl, —(SO2)NRbRb, hydroxyC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —(CReRe)mCN, —C(═O)NRbRb, —C(═O)ORb, —N(CReRe)mA, —N(Re)(CReRe)mA, —(C═N)OC1-6alkyl, —(C═O)N(Re)(CReRe)mA, (C═O)N(Re)(CReRe)mCF3, —O(CReRe)mA, —O(CReRe)mOA or —C(═O)A; A is a 4 to 9 membered aryl, heteroaryl or heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have from 1 to 3 heteroatoms independently selected from O, N or S, or a 3 to 6 membered cycloalkyl group, and the aryl, heteroaryl, heterocycloalkyl or cycloalkyl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, —(CReRe)mOH, hydroxyC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN, —C(═O)NRbRb, —O(CReRe)mB or —(CReRe)mB; B is a 5 to 6 membered aryl, heteroaryl or heterocycloalkyl group, where the heteroaryl or heterocycloalkyl group can have from 1 to 3 heteroatoms independently selected from O, N or S, or a 3 to 5 membered cycloalkyl group, and the aryl, heteroaryl, cycloalkyl or heterocycloalkyl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, hydroxyC1-6alkyl, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN or —C(═O)NRbRb; R2 is a 5 to 10 membered aryl or heteroaryl, where the heteroaryl group can have from 1 to 3 heteroatoms independently selected from O, N or S, and the aryl or heteroaryl group can be unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, —NRbRb, —C1-6alkyl, —OC1-6alkyl, hydroxyC1-6alkyl, —(CRcRc)nNRbRb, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, —OCH2F, —CN or —C(═O)NRbRb; each Rb is independently H or —C1-6alkyl; each Rc is independently H or —C1-6alkyl; and each Rd is independently H, halo, —CN, —NRcRc, —OH, —C1-6alkyl, —C1-6haloalkyl, —OC1-6haloalkyl or —OC1-6alkyl; each Re is independently H, halo, —CN, —NRcRc, —OH, —C1-6alkyl, —OC1-6alkyl or a 5 to 6 membered heterocycloalkyl group having from 1 to 3 heteroatoms independently selected from O, N or S; each n is independently 0, 1, 2, 3 or 4; each m is independently 0, 1, 2, 3 or 4.