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Efficient Synthesis of Novel 3‐Aryl‐5‐(4‐chloro‐2‐morpholinothiazol‐5‐yl)‐4,5‐dihydro‐1 H ‐pyrazoles and Their Antifungal Activity Alone and in Combination with Commercial Antifungal Agents
Author(s) -
Ramírez Juan,
Rodríguez María Victoria,
Quiroga Jairo,
Abonia Rodrigo,
Sortino Maximiliano,
Zacchino Susana A.,
Insuasty Braulio
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400084
Subject(s) - chemistry , candida albicans , cryptococcus neoformans , fluconazole , acetic acid , antifungal , hydrazine (antidepressant) , aryl , itraconazole , formic acid , amphotericin b , stereochemistry , organic chemistry , microbiology and biotechnology , biochemistry , alkyl , biology
The α,β‐unsaturated carbonyl compounds 5a – f were prepared by reaction between 2‐chloro‐4‐morpholinothiazol‐5‐carbaldehyde 3 and substituted acetophenones 4a – f . Treatment of compounds 5a – f with hydrazine hydrate employing mild reaction conditions led to the formation of 4,5‐dihydro‐1 H ‐pyrazoles 6a – f . Then the treatment with acetic anhydride or formic acid afforded the expected 4,5‐dihydro‐1 H ‐pyrazoles 7a – f and 8a – f . The antifungal activity of each series of synthesized compounds was determined against the clinically important fungi Candida albicans and Cryptococcus neoformans . In addition, the most active compounds 7e and 7f were tested in combination with the commercial antifungal agents: fluconazole, itraconazole, and amphotericin B. Compound 7e showed a synergistic effect with fluconazole against C. albicans while 7f showed synergistic activities with all tested antifungal drugs against the same yeast.