Compounds that modulate intracellular calcium
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IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07D-417/14
C07D-409/04
C07D-409/14
A61K-031/4155
C07D-413/04
출원번호
US-0432959
(2013-10-11)
등록번호
US-9512116
(2016-12-06)
국제출원번호
PCT/US2013/064633
(2013-10-11)
국제공개번호
WO2014/059333
(2014-04-17)
발명자
/ 주소
Rogers, Evan
Cao, Jianguo
Wang, Zhijun
Grey, Jonathan
Whitten, Jeffrey P.
출원인 / 주소
CALCIMEDICA, INC.
대리인 / 주소
Wilson, Sonsini, Goodrich & Rosati
인용정보
피인용 횟수 :
0인용 특허 :
91
초록▼
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
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.
대표청구항▼
1. A compound having the structure of Formula (V): wherein: R1 is aryl or heteroaryl wherein aryl or heteroaryl is optionally substituted with at least one R3;wherein aryl is selected from phenyl and napthyl,wherein heteroaryl is selected from furan, thiophene, pyrrole, oxazole, thiazole, isothiazol
1. A compound having the structure of Formula (V): wherein: R1 is aryl or heteroaryl wherein aryl or heteroaryl is optionally substituted with at least one R3;wherein aryl is selected from phenyl and napthyl,wherein heteroaryl is selected from furan, thiophene, pyrrole, oxazole, thiazole, isothiazole, imidazole, isoxazole, pyrazole, oxadiazole, thiadiazole, benzothiazole, benzoxazole, benzofuran, and indole;R2 is phenyl or pyridyl wherein each is optionally substituted with at least one R4; eachR3 is independently selected from F, Cl, Br, I, CH3, Et, CH2F, CHF2 or CF3;each R4 is independently selected from F, Cl, Br, I, CH3, CH2F, CHF2 or CF3;R5 is H, CH3, Et, isopropyl or allyl;or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1 wherein R2 is phenyl. 3. The compound of claim 2 wherein each R4 is independently selected from F and CH3. 4. The compound of claim 2 wherein each R4 is F. 5. The compound of claim 4 wherein R2 is substituted with two R4. 6. The compound of claim 4 wherein R2 is substituted with three R4. 7. The compound of claim 6 wherein R1 is heteroaryl. 8. The compound of claim 7 wherein R1 is thiazolyl. 9. The compound of claim 8 wherein R1 is unsubstituted thiazolyl. 10. The compound of claim 9 wherein R5 is CH3. 11. The compound of claim 9 wherein R5 is Et. 12. The compound of claim 9 wherein R5 is allyl. 13. The compound of claim 7 wherein R1 is pyridyl. 14. The compound of claim 13 wherein R1 is unsubstituted pyridyl. 15. The compound of claim 1 wherein R2 is pyridyl. 16. The compound of claim 1 selected from 2,6-difluoro-N-(5-(1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl)thiophen-2-yl)benzamide; 2,4,6-trifluoro-N-(5-(1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl)thiophen-2-yl)benzamide; 2-fluoro-N-(5-(3-(2-fluorophenyl)-1-methyl-1H-pyrazol-5-yl)thiophen-2-yl)-6-methylbenzamide; N-(5-(1-ethyl-3-(thiazol-2-yl)-1H-pyrazol-5-yl)thiophen-2-yl)-2,4,6-trifluorobenzamide; 2,4,6-trifluoro-N-(5-(1-methyl-3-(thiazol-2-yl)-1H-pyrazol-5-yl)thiophen-2-yl)benzamide; 2,4-difluoro-N-(5-(1-methyl-3-(thiazol-2-yl)-1H-pyrazol-5-yl)thiophen-2-yl)benzamide; 2,6-difluoro-N-(5-(1-methyl-3-(thiazol-2-yl)-1H-pyrazol-5-yl)thiophen-2-yl)benzamide; N-(5-(1-ethyl-3-(thiazol-2-yl)-1H-pyrazol-5-yl)thiophen-2-yl)-2,6-difluorobenzamide; 2,6-difluoro-N-(5-(3-(thiazol-2-yl)-1-vinyl-1H-pyrazol-5-yl)thiophen-2-yl)benzamide; 2,3,6-trifluoro-N-(5-(1-methyl-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1H-pyrazol-5-yl)thiazol-2-yl)benzamide; 2,6-difluoro-N-(5-(1-methyl-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1H-pyrazol-5-yl)thiazol-2-yl)benzamide; 2,6-difluoro-N-(4-methyl-5-(1-methyl-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1H-pyrazol-5-yl)thiazol-2-yl)benzamide; 2-fluoro-6-methyl-N-(5-(1-methyl-3-(5-methyl-1,2,4-oxadiazol-3-yl)-1H-pyrazol-5-yl)thiazol-2-yl)benzamide; 2,3,6-trifluoro-N-(5-(1-methyl-3-(thiazol-2-yl)-1H-pyrazol-5-yl)thiazol-2-yl)benzamide; and 2,6-difluoro-N-(5-methyl-2-(oxazol-2-yl)-4,5′-bithiazol-2′-yl)benzamide. 17. A pharmaceutical composition comprising a pharmaceutically acceptable diluents, excipient, or binder, and a compound of claim 1 or a pharmaceutically acceptable salt thereof. 18. A method of treating a disease, disorder or condition in a mammal selected from diseases, disorders or conditions involving inflammation, glomerulonephrititis, uvetis, hepatic diseases or disorders, renal diseases or disorders, chronic obstructive pulmonary disease, rheumatoid arthritis, inflammatory bowel disease, vasculitis, dermatitis, osteoarthritis, inflammatory muscle disease allergic rhinitis, vaginitis, interstitial cystitis, schleroderma, osteoporosis, eczema, organ transplant reject, allogeneic or xenogeneic transplantation, graft rejection, graft-versus host disease, lupus erythematosus, type 1 diabetes, pulmonary fibrosis, dermatomyositis, thyroiditis, myasthenia gravis, autoimmune hemolytic anemia, hepatitis and atopic dermatitis, asthma, psoriasis, multiple schlerosis, Sjorgren's syndrome, and autoimmune diseases or disorders comprising administering to the mammal a compound of claim 1 or a pharmaceutically acceptable salt thereof.
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