Linked Life Data

7611832

Source:http://linkedlifedata.com/resource/pubmed/id/7611832

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-8-17
pubmed:abstractText
A series of 4-(1-pyrazolyl)butanamides, pyrazolylalkyl cyanoguanidines, and related compounds with diverse functional groups (e.g. nitro, amino, guanidino groups) in the 3-position of the pyrazole ring was prepared via 4-(3-nitro-1-pyrazolyl)butanenitrile (5) and the corresponding carboxylic acid 7 as central intermediates. The amides 9a-d were prepared from the primary amines 8a-d which represent partial structures of the H2-receptor antagonists roxatidine, cimetidine, ranitidine, and famotidine. The roxatidine-derived 4-(3-nitro-1-pyrazolyl)butanamide (9a) proved to be the compound with the highest H2-receptor antagonist activity of 23 compounds tested at the isolated guinea pig right atrium preparation, achieving about 6 times famotidine's or 160 times cimetidine's potency. By contrast, in Ghosh-Schild rats 9a did not inhibit histamine-stimulated gastric acid secretion at a dosage of 0.1 mumol/kg i.v. Compounds 20a (the 3-(trifluoroethyl-guanidino)pyrazole analogue of 9a, 12a (the cyanoguanidine analogue) and N-(4-[3-(trifluoroethylguanidino)-1-pyrazolyl]butyl)cyanogua nidine (29), which are about as active as famotidine in the atrium, turned out to be very potent inhibitors of gastric acid secretion as well (e.g., 29: 74% inhibition at 0.025 mumol/kg). These compounds are comparable to famotidine in the rat stomach and by far superior to cimetidine and ranitidine in this test system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0365-6233
pubmed:author
pubmed:issnType
Print
pubmed:volume
328
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
349-58
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Synthesis and histamine H2-receptor antagonist activity of 4-(1-pyrazolyl)butanamides, guanidinopyrazoles, and related compounds.
pubmed:affiliation
Institute of Pharmacy, University of Regensburg, Germany.
pubmed:publicationType
Journal Article, In Vitro