Synthesis of progesterone heterocyclic derivatives of potential antimicrobial activity

Abstract

The aim of this work was to synthesize steroidal heterocycles and to elucidate the potential role of these compounds as antimicrobial agents. The synthesis of steroidal heterocycles containing the pyrazole, isoxazole, thiazole, pyrane, pyridine, pyridazine, or benzopyrane ring attached to the pregnene nucleus is reported. Progesterone (1) reacts with dimethyl formamide dimethyl acetal to form enamine 2. Heterocyclization of 2 with hydrazines, hydroxylamine, glycine, ethyl acetoacetate or cyanomethylene afforded novel steroidal heterocyclic derivatives. The in vitro antimicrobial evaluation showed that all synthesized compounds show activity against the used strains of Gram positive bacteria and fungi.

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Keywords

Antimicrobial, Enamine, Progesterone, Pyrane, Pyrazole, 17 (1 phenylpyrazol 3 yl)androst 4 en 3 one, 17 (2 amino 3 cyanopyran 6 yl)androst 4 en 3 one, 17 (2 hydroxy 3 acetylpyran 6 yl)androst 4 en 3 one, 17 (2 hydroxy 3 cyanopyran 6 yl)androst 4 en 3 one, 17 (3 cyanomethylpyridazin 6 yl)androst 4 en 3 one, 17 (isoxazol 6 yl)androst 4 en 3 one, 17 (pyrazol 3 yl)androst 4 en 3 one, 17 (pyrol 3 yl)androst 4 en 3 one, 20 (1 phenyl 2 cyanopropenoylhydrazono)pregn 4 en 3 one, 20 (4 oxothiazol 2 acetylhydrazonyl 2 yl)pregn 4 en 3 one, 20 (coumarin 3 carbohydrazonyl)pregn 4 en 3 one, 20 (cyanoacetylhydrazono)pregn 4 en 3 one, 20 hydrazono n (4 amino 3 cyano 2,6 dioxopyridin 1 yl)pregn 4 en 3 one, 20 hydrazono n (4,6 dimethyl 2 oxopyridin 1 yl)pregn 4 en 3 one, 21 (dimethylaminoacryloyl 20 (ethylacetoacetato)pregn 4 en 3 one, ampicillin, benzo[a]pyrene, cycloheximide, enamine, isoxazole, progesterone, pyran derivative, pyrazole, pyridazine, thiazole, unclassified drug, antimicrobial activity, article, Bacillus cereus, Bacillus subtilis, Candida albicans, controlled study, cyclization, drug structure, drug synthesis, Escherichia coli, in vitro study, nonhuman, nuclear magnetic resonance spectroscopy, physical chemistry, Pseudomonas aeruginosa, Anti-Infective Agents, Drug Design, Drug Evaluation, Preclinical, Fungi, Gram-Negative Bacteria, Gram-Positive Bacteria, Microbial Sensitivity Tests, Molecular Structure, Progesterone, Steroids, Heterocyclic, Structure-Activity Relationship

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