2-[[[2-[(HYDROXYACETYL)AMINO]-4-PYRIDINYL]METHYL]THIO]-N-[4-(TRIFLUOROMETHOXY)PHENYL]-3-PYRIDINECARBOXAMIDE BENZENESULFONATE, CRYSTALS OF SAME, POLYMORPHS THEREOF, AND METHODS FORPRODUCTION THEREOF

摘要

In the development of 2-[[[2-[(hydroxyacetyl)amino] -4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy)phenyl]-3- pyridinecarboxamide (compound (A)), there exist several complex problems: (1) compound (A) or salts thereof are difficult of recrystallization, said salts being considerably different in storage stability, and it is very difficult to obtain a salt of compound (A) having high storage stability; (2) in the crystallization process of compound (A), the control of polymorphism is very difficult; (3) compound (A) (in the free form) causes mineral deposition in the stomach when oral-administered repeatedly; and so on. In order to solve the problems, studies have been made with attention being paid to the kinds of salts. As a result, it has been found that benzensulfonate (salt) of compound (A) has the following properties: (1) in a one-week preliminary stability test (severe test), benzensulfonate of compound (A) is not decomposed by light, humidity, or other factors, thus being unproblematic in storage stability; (2) two kinds of crystal forms are prsent, and the crystal forms can be selectively produced by a certain method; and (3) no mineral deposition in the stomach is observed even after four-week repeated oral administration.