Invention Grant
US09029398B2 2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide benzenesulfonate, crystal of same, crystal polymorph thereof, and methods for production thereof
有权
2 - [[[2 - [(羟基乙酰基)氨基] -4-吡啶基]甲基]硫基] -N- [4-(三氟甲氧基)苯基] -3-吡啶甲酰胺苯磺酸盐,其结晶,晶体多晶型物, 生产
- Patent Title: 2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide benzenesulfonate, crystal of same, crystal polymorph thereof, and methods for production thereof
- Patent Title (中): 2 - [[[2 - [(羟基乙酰基)氨基] -4-吡啶基]甲基]硫基] -N- [4-(三氟甲氧基)苯基] -3-吡啶甲酰胺苯磺酸盐,其结晶,晶体多晶型物, 生产
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Application No.: US13384590Application Date: 2010-07-16
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Publication No.: US09029398B2Publication Date: 2015-05-12
- Inventor: Masashi Niwa , Hiroshi Deguchi
- Applicant: Masashi Niwa , Hiroshi Deguchi
- Applicant Address: JP Osaka
- Assignee: Santen Pharmaceutical Co., Ltd.
- Current Assignee: Santen Pharmaceutical Co., Ltd.
- Current Assignee Address: JP Osaka
- Agency: Foley & Lardner LLP
- Priority: JP2009-169130 20090717
- International Application: PCT/JP2010/062071 WO 20100716
- International Announcement: WO2011/007870 WO 20110120
- Main IPC: C07D213/82
- IPC: C07D213/82 ; A61K31/455 ; C07D401/12
![2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide benzenesulfonate, crystal of same, crystal polymorph thereof, and methods for production thereof](/abs-image/US/2015/05/12/US09029398B2/abs.jpg.150x150.jpg)
Abstract:
In the course of developing 2-[[[2-[(hydroxyacetyl)amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide (compound A), there are the multiple problems: 1) compound A or its salt is difficult to be recrystallized, the storage stability largely differs depending on the kind of the salt, and it is very difficult to obtain a salt of compound A having excellent storage stability; 2) in a crystallization process of compound A, it is very difficult to control a crystal polymorph, and 3) compound A (free body) causes mineral deposition in the stomach when it is orally administered repeatedly. For solving these problems, we made examination focusing on the kind of the salt and, as a result, found that 1) benzenesulfonate of compound A does not decompose by light, humidity and other factors in a 1-week preliminary stability test (severe test), and has no problem in its storage stability, 2) a method of selectively producing two kinds of crystal forms of benzenesulfonate of compound A, and that 3) no mineral deposition in the stomach is observed even after a 4-week repeated oral administration.
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