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Histamine Analogues, XXXV: 2‐Substituted Histamine Derivatives Containing Classical Moieties of H 2 ‐Antagonists ‐ a Novel Class of H 1 ‐Agonists
Author(s) -
Zingel Volkmar,
Elz Sigurd,
Schunack Walter
Publication year - 1993
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19933260306
Subject(s) - histamine , chemistry , imidazole , stereochemistry , ileum , combinatorial chemistry , biochemistry , pharmacology , medicine
A new type of H 1 ‐agonists resulted from the combination of the essential histamine structure with parts of H 2 ‐antagonists. 2,4‐Disubstituted imidazole derivatives were synthesized by reaction of imidic acid methyl esters with 1,3‐dihydroxypropanone, 1,4‐dihydroxybutanone or 2‐oxo‐4‐phthalimido‐1‐butylacetate in liquid NH 3 . 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 H 1 ‐activity on the isolated guinea‐pig ileum and for H 2 ‐antagonistic activity on the isolated guinea‐pig right atrium. The substances are comparably weak H 1 ‐agonists and moderate H 2 ‐blockers.