发明名称 |
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 |
摘要 |
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. |
申请公布号 |
US9546140(B2) |
申请公布日期 |
2017.01.17 |
申请号 |
US201615150901 |
申请日期 |
2016.05.10 |
申请人 |
SANTEN PHARMACEUTICAL CO., LTD. |
发明人 |
Niwa Masashi;Deguchi Hiroshi |
分类号 |
C07D213/82;A61K31/455;C07D401/12;C07C303/32;C07C309/29 |
主分类号 |
C07D213/82 |
代理机构 |
Foley & Lardner LLP |
代理人 |
Foley & Lardner LLP |
主权项 |
1. A method of producing benzenesulfonate of 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl] methyl] thio]-N-[4-(trifluoromethoxy) phenyl]-3-pyridinecarboxamide, comprising the step of adding 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl] methyl] thio]-N-[4-(trifluoromethoxy) phenyl]-3-pyridinecarboxamide to an organic solvent solution containing benzenesulfonic acid. |
地址 |
Osaka JP |