Substituted sulfonamide derivative and a pharmaceutical composit

Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...

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544363, C07D40112, C07D24308, C07D295067, C07D295104

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053268709

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BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a novel substituted sulfonamide derivative and a pharmaceutical composition comprising the same. More particularly, the present invention is concerned with a substituted sulfonamide derivative, in which the S atom of a sulfonamide moiety has, bonded thereto, a quinolyl group, an isoquinolyl group, a benzothiazolyl group or a quinazolin-4-on group and the N atom of the sulfonamide moiety has, bonded thereto via a methylene group or an alkylene group, a piperazinyl group or a homopiperazinyl group, or an acid addition salt of the substituted sulfonamide derivative. The substituted sulfonamide derivative or acid addition salt thereof according to the present invention affects the bronchial smooth muscle of a mammal and is useful as an active ingredient of a pharmaceutical composition for the prevention and treatment of respiratory diseases, such as asthma. The present invention also relates to a pharmaceutical composition comprising the above-mentioned novel substituted sulfonamide derivative or acid addition salt thereof as an active ingredient.


BACKGROUND ART

Various compounds have been proposed as a drug for the treatment of respiratory diseases, such as a vasodilator, a cerebral circulation ameliorator and a drug for the treatment of angina and the like. In this connection, reference may be made to, for example, European Patent No. 0061673 (corresponding to U.S. Pat. No. 4,456,757, U.S. Pat. No. 4,560,755, U.S. Pat. No. 4,525,589, Japanese Patent Application Laid-Open Specification No. 57-156463, Japanese Patent Application Laid-Open Specification No. 57-200366, Japanese Patent Application Laid-Open Specification No. 58-121278, and Japanese Patent Application Laid-Open Specification No. 58-121279), European Patent No. 0109023 (corresponding to U.S. Pat. No. 4,634,770, U.S. Pat. No. 4,709,023, Japanese Patent Application Laid-Open Specification No. 59-93054, and Japanese Patent Application Laid-Open Specification No. 60-81168), U.S. Pat. No. 4,678,783 (corresponding to Japanese Patent Application Laid-Open Specification No. 61-152658 and Japanese Patent Application Laid-Open Specification No. 61-227581), U.S. Pat. No. 4,798,897 (corresponding to Japanese Patent Application Laid-Open Specification No. 62-103066 and Japanese Patent Application Laid-Open Specification No. 62-111981), Journal of Medicinal Chemistry, 32, 42-50 (1989), Agents Actions 28 (3-4), 173-184 (1989), and Pharmacology, 37 (3), 187-194 (1988).
In Japanese Patent Application Laid-Open Specification No. 2-184673, sulfonamides were proposed as a drug for the treatment of respiratory diseases. In Japanese Patent Application Laid-Open Specification Nos. 2-073067 and 2-073068, quinolines and isoquinolines were proposed as a drug for the prevention and treatment of respiratory diseases.
It is known in the art that N-(2-aminoethyl)-N-hexyl-5-isoquinolinesulfonamide and 1-(5-isoquinolinesulfonyl)-3-aminopiperidine disclosed in U.S. Pat. No. 4,798,897 and N-(2-guanidinoethyl)-5-isoquinolinesulfonamides disclosed in Agents Actions, vol. 28, No. 3-4, pp 173-184 (1989), Pharmacology, vol. 37, No. 3, pp 187-194 (1988) and European Patent No. 0109023 have not only a vasodilating effect but also a bronchodilating effect. It is also known in the art that N-[2-3,4-methylenedioxybenzylamino)ethyl]-8-chloro-5-quinolinesulfonamides have a brochodilating effect. However, the vasodilating and bronchodilating effects of the above compounds are not satisfactory.
Bronchodilators, such as xanthine type medicines and .beta.-receptor stimulants, are widely used as a clinical, therapeutic agent for the treatment of respiratory diseases, such as asthma. As a representative example of the xanthine type medicines, aminophylline can be mentioned. Further, as a representative example of the .beta.-receptor stimulants, isoproterenol can be mentioned However, these xanthine type medicines and .beta.-receptor stimulants have side effects on the heart and the like, and an intractable asthma which is not remitted by these med

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