COMPOUNDS THAT MODULATE INTRACELLULAR CALCIUM

摘要

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.

主权项

1. A compound having the structure of Formula (VI):wherein
R′1 is L2 is Z—C(R12)2 or —C(R12)2N(R5)—; Z is O, S, S(O), or NR5; X is CR3 or N; Y is independently selected from CR9 and N; R2 is C1-C6alkyl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C8heterocycloalkyl, C1-C4alkyleneC2-C8heterocycloalkyl, aryl, heteroaryl, fused aryl or fused heteroaryl; wherein C1-C6alkyl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C8heterocycloalkyl, C1-C4alkyleneC2-C8heterocycloalkyl, aryl, heteroaryl, fused aryl or fused heteroaryl is optionally substituted with at least one R3; R3 is independently selected from H, F, D, Cl, Br, I, —CN, —NO2, —OH, —CF3, —OCF3, —OR5, C1-C6alkyl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C8heterocycloalkyl, optionally substituted aryl, optionally substituted O-aryl, or optionally substituted heteroaryl; n is an integer selected from 0-2; R9 is independently selected from H, D, halogen, C1-C6alkyl, C1-C6haloalkyl, —OR5, —OCF3, C1-C6 carbonylalkyl, and —CF3; or two R9 attached to the same carbon atom form an oxetane ring; R10 is selected from halogen, C1-C6alkyl, C1-C6haloalkyl, —OR5, —OCF3, C1-C6 carbonylalkyl, and —CF3; R5 is independently selected from H, C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, phenyl, and benzyl; R12 is independently selected from H, D, halogen, —CN, —CF2H, CF3, C1-C6alkyl, —NH—C(O)R, and C(O)NHR5; or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.