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 metadata

Field	Value
Publication number	US-9359328-B2
Application number	US-201514686577-A
Country	US
Kind code	B2
Filing date	Apr 14, 2015
Priority date	Jul 17, 2009
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

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.

First claim

The invention claimed is:

1. A crystal of benzenesulfonate of 2-[[[2-[(hydroxyacetyl) amino]-4-pyridinyl]methyl]thio]-N-[4-(trifluoromethoxy) phenyl]-3-pyridiriecarboxamide having characteristic peaks at 4.4 angstroms, 3,8 angstroms and 2,3 angstroms as a d value of powder X-ray diffraction pattern.

2. A crystal of benzenesulfonate of 2-[[[2-((hydroxyacetyl) amino]-4-pyridinyl]methyl]thio]-N[4-(trifluoromethoxy) phenyl]-3-pyridinecarboxamide having characteristic peaks at 8.1 angstroms, 6.8 angstroms, 4.1 angstroms and 4.0 angstroms as a d value of powder X-ray diffraction pattern.

Assignees

• Santen Pharmaceutical Co Ltd

Inventors

• Niwa Masashi
• Deguchi Hiroshi

Classifications

• A61P7/10

  Antioedematous agents; Diuretics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title