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US 2012/0071516 A1Published application
Compounds that modulate intracellular calcium
AssigneeCalcimedica, Inc.
InventorsJianguo Cao, Jeffrey P. Whitten, Yazhong Pei, Zhijun Wang, Evan Rogers, Jonathan Grey
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Abstract
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.
Claims26
A compound of Formula (I) or Formula (II):
- wherein:
- X is CR1 or N;
- L1 and L2 are each independently a bond, NR4S(═O)2, S(═O)2N(R4), —C(═O)NR4S(═O)2, —S(═O)2NR4C(═O), N(R4), —N(R4)C(═O), —CO2, —C(═O), —OC(═O), —C(═O)N(R4), —S, —O, —S(═O), —S(═O)2, —C(═O)N(R4)—C1-C6alkylene, —N(R4)C(═O)—C1-C6alkylene, C1-C6alkylene, C2-C6alkenylene, C2-C6alkynylene, C1-C6heteroalkylene, C3-C6cycloalkylene, or C2-C6heterocycloalkylene, wherein C1-C6alkylene, C2-C6alkenylene, C2-C6alkynylene, C1-C6heteroalkylene, C3-C6cycloalkylene, and C2-C6heterocycloalkylene is optionally substituted with at least one R6;
- A and B are each independently C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6heteroalkyl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, aryl, or heteroaryl wherein C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6heteroalkyl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, aryl, or heteroaryl is each optionally substituted with at least one R2;
- R2 is selected from D, F, Cl, Br, I, —CN, —NO2, —CF3, —OH, —OR3, —OCF3, —C≡CR5, C1-C6alkylenealkyne, C1-C6alkyl, C2-C6alkene, C2-C6alkyne, C3-C6cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C6heterocycloalkyl, aryl, heteroaryl, —NHS(═O)2R4, S(═O)2N(R4)2, —C(═O)CF3, —C(═O)NHS(═O)2R4, —S(═O)2NHC(═O)R4, N(R4)2, —N(R4)C(═O)R4, —CO2R4, —C(═O)R4, —OC(═O)R4, —C(═O)N(R4)2, —SR4, —S(═O)R4, and —S(═O)2R4;
- wherein C1-C6alkylenealkyne, C1-C6alkyl, C2-C6alkene, C2-C6alkyne, C3-C6cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C6heterocycloalkyl, aryl, heteroaryl is optionally substituted with at least one R6;
- or optionally two R2 are joined to form a five or six membered heterocyclic ring;
- R1 is H, halogen, C1-C6alkyl, C3-C6cycloalkyl, CO2R5 or a carboxylic acid bioisostere;
- R5 is H, C1-C6alkyl, C3-C6cycloalkyl, C1-C6haloalkyl, phenyl or benzyl;
- R is H, D, F, Cl, Br, I, —CN, —NO2, —CF3, —OH, —OR3, —OCF3, —C≡CR5, C1-C6alkylenealkyne, C1-C6alkyl, C2-C6alkene, C2-C6alkyne, C3-C6cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C6heterocycloalkyl, aryl, heteroaryl, —NHS(═O)2R4, S(═O)2N(R4)2, —C(═O)CF3, —C(═O)NHS(═O)2R4, —S(═O)2NHC(═O)R4, N(R4)2, —N(R4)C(═O)R4, —CO2R4, —C(═O)R4, —OC(═O)R4, —C(═O)N(R4)2, —SR4, —S(═O)R4, and —S(═O)2R4;
- wherein C1-C6alkyl, C2-C6alkene, C2-C6alkyne, C3-C6cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C6heterocycloalkyl, aryl, heteroaryl is optionally substituted with at least one R6;
- each R3 is independently selected from C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, phenyl, and benzyl;
- each R4 is independently selected from hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, phenyl, and benzyl;
- R6 is selected from D, F, Cl, Br, I, —CN, —NO2, —CF3, —OH, —OR3, —OCF3, —C≡CR5, C1-C6alkyl, C3-C6cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C6heterocycloalkyl, aryl, heteroaryl, —NHS(═O)2R4, S(═O)2N(R4)2, —C(═O)CF3, —C(═O)NHS(═O)2R4, —S(═O)2NHC(═O)R4, N(R4)2, —N(R4)C(═O)R4, —CO2R4, —C(═O)R4, —OC(═O)R4, —C(═O)N(R4)2, —SR4, —S(═O)R4, and —S(═O)2R4;
- or
- a pharmaceutically acceptable salt, solvate, N-oxide or prodrug thereof.
13 more elements
A compound selected from:
- or a pharmaceutically acceptable salt, solvate, N-oxide or prodrug thereof.
Dependencies are inferred from the claim text.