Pyrrolopyrazine-spirocyclic piperidine amides as modulators of ion channels

摘要

The invention relates to pyrrolopyrazine-spirocyclic piperidine amide compounds of formula (I) useful as inhibitors of ion channels:;
wherein R1, R2, R3, R4, A, m, n, and o are as defined in the description. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

主权项

1. A compound of formula I:or a pharmaceutically acceptable salt thereof,wherein, independently for each occurrence:
R1 is H, C1-C8 alkyl, C3-C8 cycloalkyl, halo, CN, NR8SO2R8, SO2R8, SR8, SOR8, NR8COR8, NR8CO2R8, CON(R8)2, SO2N(R8)2, CF3, heterocycloalkyl, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2 or NR8, or two R1 taken together form an oxo group; R2 is H, C1-C8 alkyl, halo, C1-C8 haloalkyl, CN, OH, SO2R8, SR8, SOR8, COR8, CO2R8, CON(R8)2, SO2N(R8)2, CF3, CHF2, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2, CF2, or NR8; R3 is H, C1-C8 alkyl, C3-C8 cycloalkyl, CO2R8, COR8, COH, CON(R8)2, CF3, CH2CF3, CH2CHF2, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2 or NR8; R4 is H, C1-C8 alkyl, halo, C3-C8 cycloalkyl, wherein up to two CH2 units may be replaced by O, CO, S, SO, SO2, or NR8, or 2 R4 taken together form a fused 3 to 7 membered cycloalkyl ring; R8 is H, C1-C8 alkyl, CF3, C3-C8 cycloalkyl, fluoroalkyl, aryl, heteroaryl, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2 or NR, or 2 R8 taken together with the atoms to which they are attached form a ring; R9 is H, CF3, CO2R, OH, aryl, heteroaryl, C3-C8 cycloalkyl, heterocycloalkyl, N(R)2, NRCOR, CON(R)2, CN, halo, or SO2R; R is H, C1-C8 alkyl, aryl, heteroaryl, C3-C8 cycloalkyl, or heterocycloalkyl; A is an aryl optionally substituted with one or more of C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 alkoxy, C3-C8 cycloalkoxy, halo, CN, OH, OR8, N(R8)2, NR8SO2R8, OSO2R8, SO2R8, SOR8, SR8, CO2R8, NR8COR8, NR8CO2R8, CON(R8)2, SO2N(R8)2, CHF2, CF3, OCF3, OCHF2, R9, heterocycloalkyl, heterocycloalkoxy, aryl, heteroaryl, or a straight chain, branched, or cyclic (C3-C8)-(R9)p wherein p is 1 or 2 and wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2, or NR8; or wherein two adjacent substituents on A together with the carbons to which they are attached form a ring comprising up to 2 heteroatoms; m is 0, 1, 2, 3, or 4; n is 0, 1, 2, or 3; and o is 0, 1, 2, 3, or 4.