Synthesis and biological evaluation of [α-(1,5-disubstituted 1 H-pyrazol-4-yl)benzyl]azoles, analogues of bifonazole

• Published in: Farmaco (Società chimica italiana : 1989) 1999-06, Vol.54 (6), p.416-422
• Main Authors: Menozzi, Giulia, Mosti, Luisa, Bruno, Olga, Lo Presti, Eleonora, Musiu, Chiara, Longu, Silvia, La Colla, Paolo, Filippelli, Walter, Falcone, Giuseppe, Piucci, Brunella
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Anti-Arrhythmia Agents - chemical synthesis; Anti-Arrhythmia Agents - pharmacology; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Antiarrhythmic agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Antihypertensive Agents - chemical synthesis; Antihypertensive Agents - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Azole derivatives; Bifonazole analogues; Biological and medical sciences; Drug Screening Assays, Antitumor; Fungi - drug effects; Hemodynamics - drug effects; HIV-1 - drug effects; Imidazoles - chemical synthesis; Imidazoles - pharmacology; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Rats; Salmonella - drug effects; Spectrophotometry, Infrared
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/S0014-827X(99)00036-1

A series of pyrazole analogues of bifonazole, an antifungal drug used in clinical practice, 2a–h and 4a–h were synthesized and tested in vitro against Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, with no significant results. Imidazoles 2a–h were also tested in vivo for antiarrhythmic and antihypertensive activities; two of these compounds showed moderate activity against ventricular fibrillation caused by aconitine in rats. The above compounds were prepared by reaction of phenyl-[5 substituted 1-phenyl (or 1-methyl)-1 H-pyrazol-4-yl]methanols with N,N′-carbonyldiimidazole ( 2a–h) or of the respective chloro derivatives with 1 H-1,2,4-triazole ( 4a–h).