Document Detail


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.
MedLine Citation:
PMID:  2892935     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
6-[4-[3-[[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 vasodilation 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.
Authors:
W Howson; J Kitteringham; J Mistry; M B Mitchell; R Novelli; R A Slater; G T Swayne
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  31     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1988 Feb 
Date Detail:
Created Date:  1988-03-16     Completed Date:  1988-03-16     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  352-6     Citation Subset:  IM    
Affiliation:
Smith Kline & French Research Ltd., Welwyn, Hertfordshire, U.K.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / chemical synthesis*,  pharmacology
Animals
Antihypertensive Agents / chemical synthesis*,  pharmacology
Cats
Pyridazines / chemical synthesis*,  pharmacology
Rats
Stereoisomerism
Vasodilator Agents / chemical synthesis*,  pharmacology
Chemical
Reg. No./Substance:
0/6-(4-(3-((2-hydroxy-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propyl)amino)propionamido)phenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone; 0/Adrenergic beta-Antagonists; 0/Antihypertensive Agents; 0/Pyridazines; 0/Vasodilator Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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