Acta Pharm. 56 (2006) 203-218

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Original research paper  

Synthesis of some new testosterone derivatives fused with substituted pyrazoline ring as 5alpha-reductase inhibitors


1Applied Organic Chemistry Dept., National Research Centre, Dokki, Cairo, Egypt
2Natural Compounds Chemistry Dept., National Research Centre, Dokki, Cairo, Egypt
3Research Units, Egyptian Pharmacist Co., Cairo, Egypt
Accepted February 1, 2006

Condensation of 3-hydroxy-16-[(4-chlorophenyl)methylene]androst-5-en-17-one (1) with hydrazine hydrate in acetic acid afforded N-acetyl pyrazoline derivative 2, while, condensation of 1 with semicarbazide afforded compound 3. Also, compound 1 was treated with hydrazine hydrate in absolute methanol or ethanol to afford the corresponding alpha-methoxy (4) and alpha-ethoxy (5) derivatives, which were cyclized with etherated boron trifluoride to the pyrazoline derivative 6. The latter could be prepared directly by refluxing 1 with hydrazine hydrate in dioxane. Oxidation of compound 6 with Oppenour or Moffat oxidizing agents yielded 3-oxo-derivatives 7 and 8, respectively. On the other hand, condensation of compound 1 with substituted hydrazines, gave the corresponding 3beta-hydroxyandrostenopyrazolines 9a,b, which were oxidized using the Moffat method give 3-oxo-androstenopyrazolines 10a,b, which were condensed with ethylene triphenyl-phosphorane in DMSO to yield 3-ethylene androstenopyrazolines 11a,b. Dehydrogenation of 9a,b with Wettestein oxidation afforded delta4,6-diene-3-one analogues 12a,b, which were treated with chloranil to yield delta4,6,8(14)-triene-3-one analogues 13a,b. Oppenour oxidation of 9a,b afforded delta4-ene-3-one analogues 14a,b, which were treated with dichlorodicyanoquinone (DDQ) in dioxane to give delta1,4,6-triene-3-one analogues 15a,b. Pharmacological screening showed that many of these compounds inhibit 5alpha-reductase activity.

Keywords: testosterone, pyrazolines, Moffat oxidation, 5alpha-reductase inhibitor, pharmacological screening