Synthesis and Structure-Activity Relationships of a New Series of Benzimidazoles as H1-Antihistaminic Agents

• Published in: Chemical & pharmaceutical bulletin Vol. 45; no. 8; pp. 1287 - 1292
• Main Authors: CUBERES, Maria Rosa, CONTIJOCH, Montserrat, CALVET, Carme, ALEGRE, Julia, QUINTANA, Jordi Ramon, FRIGOLA, Jordi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1997; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; azolyl-butyl-piperazinyl (or homopiperazinyl)benzimidazole; Benzimidazoles - chemical synthesis; Benzimidazoles - pharmacology; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Guinea Pigs; H1-antihistaminic drug; Histamine and antagonists. Allergy; Histamine H1 Antagonists - chemical synthesis; Histamine H1 Antagonists - pharmacology; In Vitro Techniques; Male; Medical sciences; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; p-Methoxy-N-methylphenethylamine - toxicity; Pharmacology. Drug treatments; Potentiometry; Rats; Rats, Wistar; Spectrophotometry, Ultraviolet; Structure-Activity Relationship; structureactivity relationship; synthesis; Intraperitoneal administration; Rat; Nitrogen heterocycle; Azole derivatives; Central nervous system; Antihistaminic; Guinea pig; Structure activity relation; Bicyclic compound; Pyrazole derivatives; Aromatic compound; Antagonist; Chemical synthesis; Digestive system; Rodentia; Gut; Ileum; In vitro; H1 receptor; In vivo; Vertebrata; Mammalia; Animal; Piperazine derivatives; Brain (vertebrata)
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.45.1287

New 2-(4-(4-azolybutyl)piperazinyl)-, 2-(4-(4-azolybutyl)piperazinylmethyl)-, 2-(4-(4-azolylbutyl)homopiperazinyl)- and 2-(4-(4-azolylbutyl)homopiperazinyl)methylbenzimidazoles were synthesized, characterized and tested for in vitro and in vivo H1-antihistaminic activity. Structure-activity relationships impleid 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-l-yl)butyl]homopiperazin-l-yl}benzimidazole (17), at its dimaleate salt, has been chosen for further development.