Referenced in: none

Automatically associated channels: Kir2.3

Title: Novel potassium channel activators. II. Synthesis and pharmacological evaluation of 3,4-dihydro-2H-1,4-benzoxazine derivatives: modification of the aromatic part.

Authors: Y Matsumoto, R Tsuzuki, A Matsuhisa, N Masuda, Y Yamagiwa, I Yanagisawa, T Shibanuma, H Nohira

Journal, date & volume: Chem. Pharm. Bull., 1999 Jul , 47, 971-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/10434398

Abstract
Three new series of analogues related to 3,4-dihydro-2H-1,4-benzoxazine derivative 1a were synthesized and evaluated for their potassium channel activating activity. In the first series I, where the 6,7-positions were disubstituted, it was found that an electron-withdrawing substituent was preferable at the 6 position, but either an electron-withdrawing or releasing substituent without bulkiness was tolerated at the 7 position. In the second series II, where several heterocycles were introduced into the 6,7-positions, the oxadiazole derivative 6 showed more potent activity than cromakalim. In the third series III, where the benzene ring was replaced by a pyridine ring, borane complex 16 had equivalent activity to cromakalim. Especially, compound 6 showed a potent hypotensive effect with a long duration of action in the spontaneous hypertensive rat and had a lesser increasing effect on intracranial pressure in dogs than 1a and levcromakalim, showing a good profile as an antihypertensive agent.