2 - 2 - (HYDROXYACETYL) AMINO -THEALS OF THE PRODUCTS PYRIDINYL METHYL THIO -N- 4- (NON-TRIFF-TORMETOXY) FENIL -3-PYRIDIN-CARBOXAMIDE, ITS CRYSTALS -3-Pyridinecarboxamide, Its Crystals, 3-Pyrydinecarboxamide, Its Crystals, 3-Pyrene Carboxyxide, Its Crystals, 3-Pyridinecarboxamide, Its Crystals, 3)

摘要

Upon receipt of 2 - [[[2 - [(hydroxyacetyl) amino] -4-pyridinyl] methyl] thio] -N- [4- (trifluoromethoxy) phenyl] -3-pyridinecarboxamide (compound A) many problems arise: 1) A or its salt is difficult to recrystallize, storage stability varies greatly depending on the type of salt and it is very difficult to obtain the salt of compound A with good storage stability; 2) during the crystallization of compound A, it is very difficult to control the crystalline polymorph; and 3) compound A (free form) causes deposition of minerals in the stomach when it is repeatedly administered orally. To solve these problems, the authors, during the development process, concentrated their attention on the type of salt and found that, as a result, 1) benzenesulfonate of compound A does not decompose under the action of light, moisture and other external factors, evaluated during a 1-week preliminary stability test (hard test ), and does not create problems with storage stability, 2) a method has been developed for the selective production of two types of crystalline forms of compound A benzenesulfonate; and in this case, 3) the deposition of mineral compounds in the stomach is not observed even after 4 weeks of repeated oral administration.