Histaprodifens: synthesis, pharmacological in vitro evaluation, and molecular modeling of a new class of highly active and selective histamine H(1)-receptor agonists.

A new class of histamine analogues characterized by a 3, 3-diphenylpropyl substituent at the 2-position of the imidazole nucleus has been prepared outgoing from 4,4-diphenylbutyronitrile (4b) via cyclization of the corresponding methyl imidate 5b with 2-oxo-4-phthalimido-1-butyl acetate or 2-oxo-1,4-butandiol in liquid ammonia, followed by standard reactions. The title compounds displayed partial agonism on contractile H(1) receptors of the guinea-pig ileum and endothelium-denuded aorta, respectively, except 10 (histaprodifen; 2-[2-(3, 3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine) which was a full agonist in the ileum assay. While 10 was equipotent with histamine (1), methylhistaprodifen (…

(8,9-Dihydro-7H-imidazo[1,2-c][1,3]diazepin-5-yl)-cyanamide und homologe imidazo-bizyklen

Die Reaktion der 2-(ω-Aminoalkyl)-imidazole 4a-f mit N-Cyanodiphenyl-imidocarbonat (7) fuhrt zu den entsprechend hydrierten Imidazo[1,5-a]imidazolen, Imidazo[1,2-c][1,3]diazepinen und Imidazo[1,2-c][1,3]diazocinen (9a-f), die im Verhalten gegenuber Nucleophilen und in ihren spektroskopischen Eigenschaften den (7,8-Dihydro-imidazo[1,2-c]pyrimidin-5-yl)-cyanamiden (3) [1] vergleichbar sind. The reaction of the 2-(ω-aminoalkyl)imidazoles 4a-f with N-cyanodi-phenylimidocarbonate (7) leads to appropriately hydrogenated imidazo-[1,5-a]imidazoles, imidazo[1,2-c][1,3]diazepines and imidazo[1,2-c][1,3]diazocines (9a-f), which are similar to (7,8-dihydroimidazo)[1,2-c]pyrimidin-5-yl)cyanamides (3)[1]…

ChemInform Abstract: H2-Antihistaminics. Part 35. Synthesis and H2-Antagonistic Activity of Imidazolylmethylthioalkyl-Substituted 1,2,4-Triazoles.

Abstracts of papers and posters advanced activities in pharmaceutical care 24th European Symposium on Clinical Pharmacy