1 0 0 0 アンジオテンシンⅡ受容体拮抗薬の分子設計と合成に関する研究
- 著者
- 木山 竜一 林 邦雄 原 真里子 藤本 正文 川畑 友二 川上 勝 中島 成元 藤下 利夫
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.43, no.6, pp.960-965, 1995-06-15 (Released:2008-03-31)
- 参考文献数
- 12
- 被引用文献数
- 3 8
A novel series of 6-alkyl-7-oxo-4, 7-dihydropyrazolo[1, 5-a]pyrimidine-3-carboxylic acid derivatives was prepared as angiotensin II (AII) receptor antagonists. When evaluated in an in vitro binding assay using COS cells transfected with a cDNA encoding a human AT1 angiotensin II receptor, the compounds in this series showed Ki values in the range of 0.4-4.0 nM. In anesthetized spontaneously hypertensive rats (SHRs), administration of the 6-propyl derivative 4d (1 mg/kg, i.v.) reduced the mean blood pressure (MBP) by a maximum of more than 30 mmHg from the normal value.
- 著者
- 木山 竜一 冨士 雅弘 原 真里子 藤本 正文 川畑 友二 中村 益久 藤下 利夫
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.43, no.3, pp.450-460, 1995-03-15 (Released:2008-03-31)
- 参考文献数
- 24
- 被引用文献数
- 6 7
Starting from recently reported nonpeptidic angiotensin II (AII) receptor antagonists, we have designed and prepared a new series of 6-arylimidazo[4, 5-c]pyridine derivatives. Variation of phenyl groups at the 4-, 6- or 7-position of imidazo[4, 5-c]pyridine showed that substitution at the 6-position resulted in receptor-binding activity almost as potent as that of DuP 753. This led to synthesis and evaluation of an extensive series of 6-aryl-imidazo[4, 5-c]pyridine derivatives. Some of them were 4-fold more potent in vitro than DuP 753, but only showed weak antihypertensive activity in vivo when given orally to rats.