Synthesis and structure-activity relationships of a new series of benzimidazoles as H1-antihistaminic agents.
New 2-(4-(4-azolylbutyl)piperazinyl)-, 2-(4-(4-azolylbutyl) piperazinylmethyl)-, 2-(4-(-azolylbutyl)homopiperazinyl)- and 2-(4-(4-azolylbutyl)homopiperazinylmethyl)benzimidazoles were synthesized, characterized and tested for in vitro and in vivo H1-antihistaminic activity. Structure-activity relationships implied that the best antihistaminic activity required the simultaneous presence of a homopiperazinylbenzimidazole system (or a methylene linker between the benzimidazole and the piperazine rings) and an unsubstituted pyrazole ring. 1-(2-Ethoxyethyl)-2-¿4-[4-(pyrazol-1-yl)butyl] homopiperazin-1-yl¿benzimidazole (17), as its dimaleate salt, has been chosen for further development.
Cuberes
M R
MR
Department of Medicinal Chemistry, Laboratorios Dr. Esteve, S. A., Barcelona, Spain.
Contijoch
M
M
Calvet
C
C
Alegre
J
J
Quintana
J R
JR
Frigola
J
J
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011199:Potentiometry; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D003189:p-Methoxy-N-methylphenethylamine