Document Detail


Studies on antianaphylactic agents. 7. Synthesis of antiallergic 5-oxo-5H-[1]benzopyrano[2,3-b]pyridines.
MedLine Citation:
PMID:  3989816     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
5-Oxo-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylic acids 23 and their tetrazole analogues 24 were synthesized from 4-oxo-4H-1-benzopyran-3-carbonitriles 3 or 2-amino-4-oxo-4H-1-benzopyran-3-carboxaldehydes 4. When administered intravenously, they exhibited antiallergic activity in a reaginic PCA test in rats. In the carboxylic acid series, the activity was influenced by the substituents at the 2-position and increased substantially in the following order: Me, OMe less than NH2 less than OH, H less than NHOMe. On the other hand, in the tetrazole series, 2-unsubstituted derivatives showed the highest activity. Regardless of the kinds of substituents at positions 2 and 3, compounds bearing an alkyl group, especially an isopropyl group at the 7-position, were superior in activity to the corresponding unsubstituted compounds. Among these alkyl derivatives, 3-carboxylic acid derivatives, i.e., 23c (7-ethyl), 23g (2-amino-7-isopropyl), 23r [2-(methoxyamino)-7-isopropyl], and a 3-tetrazole derivative 24c (7-isopropyl), were 41-184 times as potent as disodium cromoglycate. They also exhibited remarkable activity when administered orally; clinical studies on 23g (AA-673) are in progress.
Authors:
A Nohara; T Ishiguro; K Ukawa; H Sugihara; Y Maki; Y Sanno
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  28     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1985 May 
Date Detail:
Created Date:  1985-06-03     Completed Date:  1985-06-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  559-68     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzopyrans / chemical synthesis*,  pharmacology
Guinea Pigs
Hypersensitivity / drug therapy*
Lung / drug effects,  immunology
Male
Muscle Contraction / drug effects
Muscle, Smooth / drug effects
Passive Cutaneous Anaphylaxis / drug effects*
Pyridines / chemical synthesis,  pharmacology
Rats
Rats, Inbred Strains
SRS-A / antagonists & inhibitors,  biosynthesis
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Benzopyrans; 0/Pyridines; 0/SRS-A

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


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