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US 2004/0106537 A1Published application
Store operated calcium influx inhibitors and methods of use
AssigneeCellegy Pharmaceuticals, Inc.
InventorsThomas P. Parks, Don R. Baker
Life of this patent
Estimating the term…
Abstract
The present invention provides store operated calcium influx inhibitor compounds, pharmaceutical compositions, and methods of use. The compounds are useful for treating an inflammatory disease or treating an inflammatory reaction. Preferably, compounds, compositions and methods of this invention are used for treatment of inflammatory skin, pulmonary, musculoskeletal, and gastrointestinal diseases, as well as autoimmune disorders, transplantation treatment, and osteoporosis.
Claims83
A method for treating an inflammatory disease or reducing an inflammatory reaction, said method comprising:
- administering a SOC inhibitor, thereby treating said inflammatory disease or reducing said inflammatory reaction.
A compound having the formula
- 94
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R4 is an optionally substituted alkyl;
- and
- R5 is an optionally substituted alkyl, or alternatively, R4 and R5 and the carbons to which they are attached, joined to form an optionally substituted aryl or optionally substituted heteroalkyl 5-or 6 membered ring.
4 more elements
A compound having the formula
- 102
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is independently a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R6 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- and
- R7 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- or alternatively, R6 and R7 and the carbons to which they are attached, joined to form an optionally substituted aryl or optionally substituted heteroalkyl 5-or 6 membered ring.
5 more elements
A compound having the formula
- 108
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is independently a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R8 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R9 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- or alternatively, R8 and R9 and the carbons to which they are attached, joined to form an optionally substituted aryl or optionally substituted heteroalkyl 5-or 6 membered ring.
4 more elements
A compound having the formula
- 113
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- and
- Q is a member selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy and hydroxy.
3 more elements
A compound having the formula
- 117
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is independently a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- and
- Q is a member selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy and hydroxy.
3 more elements
A pharmaceutical composition, said pharmaceutical composition comprising:
- a compound having the formula
- 121
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R4 is an optionally substituted alkyl;
- R5 is an optionally substituted alkyl, or alternatively, R4 and R5 and the carbons to which they are attached, joined to form an optionally substituted aryl or optionally substituted heteroalkyl 5-or 6 membered ring;
- and
- a pharmaceutically acceptable excipient therefor.
6 more elements
A pharmaceutical composition, said pharmaceutical composition comprising:
- a compound having the formula
- 129
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R6 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R7 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- or alternatively, R6 and R7 and the carbons to which they are attached, joined to form an optionally substituted aryl or optionally substituted heteroalkyl 5-or 6 membered ring;
- and
- a pharmaceutically acceptable excipient therefor.
7 more elements
A pharmaceutical composition, said pharmaceutical composition comprising:
- a compound having the formula
- 130
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is independently a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R8 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- R9 is a member selected from the group consisting of an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylalkoxy;
- or alternatively, R8 and R9 and the carbons to which they are attached, joined to form an optionally substituted aryl or optionally substituted heteroalkyl 5-or 6 membered ring;
- and
- a pharmaceutically acceptable excipient therefor.
7 more elements
A pharmaceutical composition, said pharmaceutical composition comprising:
- a compound having the formula
- 131
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- Q is a member selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy and hydroxy;
- and
- a pharmaceutically acceptable excipient therefor.
5 more elements
A pharmaceutical composition, said pharmaceutical composition comprising:
- a compound having the formula
- 132
- wherein:
- R1 is a member selected from the group consisting of optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylene having at least 2 sites of unsaturation, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroaryliminooxyalkyl, optionally substituted heterocyclyl, optionally substituted oximinoaryl and optionally substituted heteroarylalkoxy;
- R2 is independently a member selected from the group consisting of optionally substituted (C1-C6)alkyl, optionally substituted (C1-C6)alkoxy, acyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy;
- Q is a member selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy and hydroxy;
- and
- pharmaceutically acceptable excipient therefor.
5 more elements
A method for blocking calcium influx from the extracellular space, said method comprising:
- contacting a cell with a store operated calcium influx (SOC) inhibitor, thereby blocking calcium influx from the extracellular space.
A method for treating inflammatory bowel disease (IBD), said method comprising:
- administering a store operated calcium influx (SOC) inhibitor, thereby treating inflammatory bowel disease (IBD).
A method of treating a disease, comprising administering a pharmaceutical composition comprising an aerosol formulation of a SOC inhibitor, wherein said disease is selected from the group consisting of acute lung injury, adult respiratory distress syndrome, asthma, interstitial lung disease, emphysema, chronic bronchitis and cystic fibrosis.
Dependencies are inferred from the claim text.