5-(Pyridinyl)-1H-benzimidazoles and 1-hydroxy-6-(pyridinyl)-1H-benzimidazoles and their cardiotonic use

US4331671A · kind A · utility

Assignee

• Sterling Drug, Inc. · US

Inventors

• George V. Lesher · Rockville Centre, US
• Baldev Singh · East Greenbush, US

Key dates

• Filing date: Jan 9, 1981
• Grant date: May 25, 1982
• Expiry date: Jan 9, 2001

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P9/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

2-R-5-(Py-Y)-1H-benzimidazole or pharmaceutically-acceptable acid-addition salt thereof, useful as a cardiotonic, is prepared by reacting 4-(Py-Y)-1,2-benzenediamine with a tri-(lower-alkyl)ortho-(lower-alkanoate) of the formula R--C(OR.sub.1).sub.3, where R is hydrogen or lower-alkyl, Y is a direct linkage or lower-alkylene having one or two carbon atoms, and Py is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, or with dimethylformamide dimethyl acetal or dimethylacetamide dimethyl acetal to produce said 2-R-5-(Py-Y)-1H-benzimidazole where R is methyl or ethyl respectively. The same compound where R is lower-alkyl is prepared in two steps by first reacting 4-(Py-Y)-1,2-benzenediamine with an alkanoylating agent providing alkanoyl of the formula ##STR1## to produce N.sub.2 --[R'--C(.dbd.O)]-4-(Py-Y)-1,2-benzenediamine and heating the latter compound to produce said 2-R'-5-(Py-Y)-1H-benzimidazole, where R' is lower-alkyl. Also shown is 1-hydroxy-2-R-6-(Py-Y)-1H-benzimidazole or pharmaceutically-acceptable acid-addition salt thereof, useful as a cardiotonic and prepared by reacting 3-nitro-N-(RCO)-4-(Py-Y)-benzeneamine with hydrogen under catalytic…