Histamine Analogues, XXXV: 2-Substituted Histamine Derivatives Containing Classical Moieties of H2-Antagonists - a Novel Class of H1-Agonists

✍ Scribed by Volkmar Zingel; Sigurd Elz; Walter Schunack

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 714 KB
• Volume: 326
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.19933260306

✦ Synopsis

A new type of H,-agonists resulted from the combination of the essential histamine structure with parts of H2-antagonists. 2,4-Disubstituted imidazole derivatives were synthesized by reaction of imidic acid methyl esters with 1,3-dihydroxypropanone, 1,4-dihydroxybutanone or 2-0x0-4phthalimido-I-butylacetate in liquid NH3. The imidazole intermediates were converted into histamine analogues by simple deprotection, Gabriel synthesis followed by deprotection, or by side-chain elongation via the nitriles and final hydrogenation. The new compounds were screened for H1-activity on the isolated guinea-pig ileum and for H2-antagonistic activity on the isolated guinea-pig right atrium. The substances are comparably weak HI-agonists and moderate H2-blockers.

In the field of histamine H2and H3-receptor research numerous potent and selective agonists have been developed in the last decade2s3), whereas in the series of HI-agonists only a limited number of compounds with reasonable potencies have been discovered up to now. However, in respect of the wide distribution of histamine receptors in mammalians, such compounds are attractive as pharmacological tools for the study of H,-effects, e.g. in human cardiology',').

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