BUSCHAUER, A and MOHR, R and SCHUNACK, W (1995) SYNTHESIS AND HISTAMINE H-2-RECEPTOR ANTAGONIST ACTIVITY OF 4-(1-PYRAZOLYL)BUTANAMIDES, GUANIDINOPYRAZOLES, AND RELATED-COMPOUNDS. ARCHIV DER PHARMAZIE, 328 (4). pp. 349-358. ISSN 0365-6233, 1521-4184
Full text not available from this repository.Abstract
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 H-2-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 H-2-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 mu mol/kg i.v, Compounds 20a (the 3-(trifluoroethylguanidino)pyrazole analogue of 9a, 12a (the cyanoguanidine analogue) and N-{4-[3-(trifluoroethylguanidino)-1-pyrazolyl]butyl}cyanoguanidine analogue) (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 mu mol/kg). These compounds are comparable to famotidine in the rat stomach and by far superior to cimetidine and ranitidine in this test system.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | H-2-ANTAGONISTIC ACTIVITY; H-2-ANTIHISTAMINICS; DERIVATIVES; STOMACH; ANALOGS; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/52609 |
Actions (login required)
 |
View Item |
