Compounds that modulate intracellular calcium
AssigneeCalcimedica, Inc.
InventorsGonul Velicelebi, Kenneth A. Stauderman, Frank King, Yazhong Pei, Jeffrey P. Whitten
Life of this patent
Estimating the term…
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, disorders or conditions that would benefit from inhibition of SOC channel activity.
Claims25
A compound of Formula (I), or pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof:
- wherein:
- L is a bond, C1-C6alkyl, C1-C6alkenyl, C1-C6heteroalkyl, aryl, or heteroaryl;
- wherein C1-C6alkyl, C1-C6alkenyl, C1-C6heteroalkyl, aryl, or heteroaryl is optionally substituted with at least one R5;
- V is a bond, O, —(C(R6)2)n—O or NR1;
- W is a bond, C1-C6alkyl, C1-C6alkenyl, C1-C6heteroalkyl;
- wherein when Y is S and X is CR3 then V and W are absent;
- X is N or CR3;
- Y is O, S or NR3, with the proviso that if Y is S, then X is not CH;
- R is CO2R1, a carboxylic acid bioisostere, an optionally substituted heteroaryl, or an optionally substituted heterocycloalkyl;
- R1 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or benzyl;
- R2 and R4 are independently an aryl, or a heteroaryl, wherein R2 and R4 are independently optionally substituted with at least one substituent selected from F, Cl, Br, I, —CN, —NO2, —OH, —CF3, —OCF3, —OR8, C1-C6alkyl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, tetrazolyl, C2-C8heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —NHS(═O)2R8, —S(═O)2N(R9)2, —N(R9)S(═O)2N(R9)2, —C(═O)CF3, —C(═O)NHS(═O)2R8, —S(═O)2NHC(═O)R8, —N(R9)2, —N(R9)C(═O)R8, —N(R9)C(═O)N(R9)2, —N(R9)C(═O)OR8, —CO2R9, —C(═O)R8, —OC(═O)R8, —OC(═O)N(R9)2, —CON(R9)2, —SR8, —S(═O)R8, and —S(═O)2R8;
- n is an integer from 1-6;
- R5 is selected from F, Cl, Br, I, —CN, —NO2, —OH, —CF3, —OCF3, —OR8, C1-C6alkyl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, tetrazolyl, C2-C8heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —NHS(═O)2R8, —S(═O)2N(R9)2, —N(R9)S(═O)2N(R9)2, —C(═O)CF3, —C(═O)NHS(═O)2R8, —S(═O)2NHC(═O)R8, —N(R9)2, —N(R9)C(═O)R8, —N(R9)C(═O)N(R9)2, —N(R9)C(═O)OR8, —CO2R9, —C(═O)R8, —OC(═O)R8, —OC(═O)N(R9)2, —CON(R9)2, —SR8, —S(═O)R8, and —S(═O)2R8;
- each R6 is independently hydrogen, F, Cl, Br, I, —CN, —NO2, —OH, —CF3, —OCF3, —OR8, C1-C6alkyl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, tetrazolyl, C2-C8heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —NHS(═O)2R8, —S(═O)2N(R9)2, —N(R9)S(═O)2N(R9)2, —C(═O)CF3, —C(═O)NHS(═O)2R8, —S(═O)2NHC(═O)R8, —N(R9)2, —N(R9)C(═O)R8, —N(R9)C(═O)N(R9)2, —N(R9)C(═O)OR8, —CO2R9, —C(═O)R8, —OC(═O)R8, —OC(═O)N(R9)2, —CON(R9)2, —SR8, —S(═O)R8, and —S(═O)2R8;
- each R8 is independently selected from C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, phenyl, and benzyl;
- each R9 is independently selected from H, C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, phenyl, and benzyl;
- and
- R3 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, C3-C8cycloalkyl, substituted or unsubstituted aryl or benzyl.
2-78. (canceled)
A method of treating a disease, disorder or condition in a mammal that would benefit from inhibition of store operated calcium channel activity comprising administering to the mammal a compound of claim 102 or pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.
(canceled)
-101. (canceled)
(canceled)
(canceled)
Dependencies are inferred from the claim text.