Synthesis and biological activity of the four stereoisomers of 6-[4-[3-[[2-hydroxy-3-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]-propionamido]phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone, a combined vasodilator and .beta.-adrenoceptor antagonist
- 1 February 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (2) , 352-356
- https://doi.org/10.1021/jm00397a014
Abstract
6-[4-[[2-Hydroxy-3-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]propionamido]phenyl-5-methyl-4,5-dihydro-3(2H)-pyridazinone (3) consists of a mixture of four stereoisomers, i.e., two racemates, as a consequence of the two asymmetric centers contained in the structure. An approximately equimolar mixture of these two racemates exhibits a novel combination of vasodilatation and .beta.-adrenergic antagonist activity. This paper describes the synthesis of each of the four possible stereoisomers of 3 and provides clear evidence for the different pharmacological profile of each of the stereoisomers. The RA,SB isomer 3a has an overall profile slightly better than the complete mixture; the other three isomers all show reduced activity as vasodilators and/or .beta.-adrenergic antagonists.Keywords
This publication has 1 reference indexed in Scilit:
- .beta.-Adrenergic blocking agents with acute antihypertensive activityJournal of Medicinal Chemistry, 1979