2,2-二烷基萘-1-酮作为新型钾通道激活剂。

2,2-Dialkylnaphthalen-1-ones as new potassium channel activators.

作者信息

Almansa C, Gómez L A, Cavalcanti F L, Rodríguez R, Carceller E, Bartrolí J, García-Rafanell J, Forn J

机构信息

Chemistry Laboratories, J. Uriach & Cía S. A., Barcelona, Spain.

出版信息

J Med Chem. 1993 Jul 23;36(15):2121-33. doi: 10.1021/jm00067a011.

DOI:10.1021/jm00067a011

PMID:8340916

Abstract

A new series of 2,2-dialkylnaphthalen-1-one potassium channel activators has been prepared, and their in vitro relaxant activities in isolated rat portal vein and guinea pig tracheal spirals as well as their oral antihypertensive effect in spontaneously hypertensive rats have been evaluated. The group of 1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethylnaphthalen -1- ones with an electron-withdrawing substituent at the 6-position contain the most active compounds and 1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonaphtha lene-6- carbonitrile, 17f (UR-8225), has been selected for further pharmacological development.

摘要

已制备了一系列新型的2,2-二烷基萘-1-酮钾通道激活剂，并评估了它们在离体大鼠门静脉和豚鼠气管螺旋条中的体外舒张活性以及在自发性高血压大鼠中的口服降压作用。在6位带有吸电子取代基的1,2-二氢-4-(1,2-二氢-2-氧代-1-吡啶基)-2,2-二甲基萘-1-酮组包含活性最高的化合物，1,2-二氢-4-(1,2-二氢-2-氧代-1-吡啶基)-2,2-二甲基-1-氧代萘-6-甲腈，即17f（UR-8225），已被选用于进一步的药理学研究。