Synthesis and biological evaluation of [alpha-(1,5-disubstituted 1H-pyrazol-4-yl)benzyl]azoles, analogues of bifonazole.
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)-1H-pyrazol-4-yl]methanols with N,N'-carbonyldiimidazole (2a-h) or of the respective chloro derivatives with 1H-1,2,4-triazole (4a-h).
Menozzi
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G
Dipartimento di Scienze Farmaceutiche, Università di Genova, Italy. menozzi@unige.it
Mosti
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Bruno
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Lo Presti
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Musiu
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Longu
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La Colla
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Filippelli
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Falcone
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Piucci
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012475:Salmonella / Q000187:drug effects; D013055:Spectrophotometry, Infrared
D000889:Anti-Arrhythmia Agents; D019380:Anti-HIV Agents; D000935:Antifungal Agents; D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D007093:Imidazoles; D011720:Pyrazoles; C036596:bifonazole