Document Detail


Synthesis and adrenergic beta-blocking activity of ortho-, meta- and para-oxypropanolamino-substituted [(benzylideneamino)oxy]propanolamines.
MedLine Citation:
PMID:  7669168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The N-isopropyl- and N-t-butyl-substituted 1-[o-(3-amino-2-hydroxypropoxy)benzylideneaminoxy]-3-amino-2-propa nols (7a,b) and their meta (8a,b) and para (9a,b) isomers, in which a single aromatic ring is substituted both by the oxypropanolaminic chain of (aryloxy)propanolaminic beta-adrenergic antagonists (AOPAs) and the [(methyleneamino)oxy]propanolaminic chain of [(methyleneamino)oxy]-propanolaminic beta-blocking drugs (MAOPAs), were synthesized and assayed for their beta-adrenergic activity by functional tests on isolated preparations. Compounds 7-9 represent a new type of molecular duplication of beta-adrenergic drugs, formally deriving from the sharing of the aromatic portions of two different pharmacophoric subunits, namely the (aryloxy)propanolaminic portion of AOPAs and the [(benzylideneamino)oxy]propanolaminic portion of aryl-substituted MAOPAs. The pharmacological results showed that the beta-blocking activity of compounds 7-9 is closely related to the way in which the two subunits are linked by the aromatic nucleus: the activity decreases on passing from the ortho-compounds (7a,b) to the meta (8a,b) and then to the para (9a,b) isomers. A comparison of this activity trend with those found for series of both beta-blocking AOPAs and aryl-substituted MAOPAs seems to indicate that compounds 7-9 can be considered more as AOPAs substituted on the phenyl ring by a [(methyleneamino)oxy]propanolaminic chain rather than as aromatic MAOPAs substituted on the same phenyl moiety by an oxypropanolaminic portion.
Authors:
A Balsamo; A Lapucci; B Macchia; M Macchia; E Orlandini; A Rossello; G Ferni; M Pinza
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Farmaco (Società chimica italiana : 1989)     Volume:  50     ISSN:  0014-827X     ISO Abbreviation:  Farmaco     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-10-18     Completed Date:  1995-10-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8912641     Medline TA:  Farmaco     Country:  ITALY    
Other Details:
Languages:  eng     Pagination:  239-43     Citation Subset:  IM    
Affiliation:
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / chemical synthesis*,  pharmacology
Animals
Guinea Pigs
Heart Atria
Male
Molecular Conformation
Myocardial Contraction / drug effects
Propanolamines / chemistry*,  pharmacology
Trachea
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Propanolamines

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


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