Document Detail


Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities.
MedLine Citation:
PMID:  2213839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of substituted indolyldihydropyridazinones and related compounds 1-18 were synthesized and evaluated for positive inotropic activity. In rats, most of these indole derivatives produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. Compound 13, 4,5-dihydro-5-methyl-6-(2-pyridin-4-yl-1H-indol-5-yl)pyrazin-3(2H) -one (BM 50.0430), was further investigated in cats. The increase in contractility in this animal model was not mediated via stimulation of beta-adrenergic receptors. After oral administration of 1 mg/kg to conscious dogs, compound 13 and pimobendan were still active after 6.5 h. However, the cardiotonic effect of 13 was at least 2-fold that of pimobendan after this period of time. The structural requirements necessary for optimal cardiotonic activity within this novel class of indole derivatives are a heterocyclic aromatic ring in position 2, a hydrogen or a methyl group in position 3, and a dihydropyridazinone ring system in position 5 of the indole.
Authors:
A Mertens; W G Friebe; B Müller-Beckmann; W Kampe; L Kling; W von der Saal
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  33     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1990 Oct 
Date Detail:
Created Date:  1990-11-20     Completed Date:  1990-11-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2870-5     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Boehringer Mannheim GmbH, Mannheim, West Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiotonic Agents / chemical synthesis*,  chemistry,  pharmacology
Cats
Chemistry, Physical
Dogs
Dose-Response Relationship, Drug
Milrinone
Molecular Structure
Myocardial Contraction / drug effects*
Physicochemical Phenomena
Pyridazines / pharmacology
Pyridones / pharmacology
Rats
Structure-Activity Relationship
Time Factors
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Pyridazines; 0/Pyridones; 74150-27-9/pimobendan; 78415-72-2/Milrinone

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