Efficient Synthesis of Novel 3-Aryl-5-(4-chloro-2-morpholinothiazol-5-yl)-4,5-dihydro-1H-pyrazoles and Their Antifungal Activity Alone and in Combination with Commercial Antifungal Agents

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‐1H‐pyrazoles 6a–f. Then the treatment with acetic anhydride or formic acid afforded the expected 4,5‐dihydro‐1H‐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. Novel 3‐aryl‐5‐(4‐chloro‐2‐morpholinothiazol‐5‐yl)‐4,5‐dihydro‐1H‐pyrazoles 7a–f and 8a–f were synthesized and their antifungal activity was tested against Candida albicans and Cryptococcus neoformans. The most active compounds 7e and 7f were screened in combination with the commercial antifungal agents, fluconazole, itraconazole, and amphotericin B. Compound 7f showed synergistic activities with all tested antifungal drugs against C. albicans.