A NEW APPROACH TO THE SYNTHESIS OF 17-PYRAZOLYLANDROSTANE
DOI:
https://doi.org/10.1007/7576Keywords:
dimethylformamide dimethylacetal, 17-pyrazolylandrostanes, 16α, 17α-epoxypregn-5-en-20-one, antiproliferative activity, condensation, breast cancer.Abstract
We propose a new approach to the synthesis of 17-pyrazolylandrostanes on the basis of 17β-[3-(dimethylamino)acryloyl]-16α,17α-epoxy-
3β-hydroxyandrost-5-ene. This epoxyandrostene was shown to react with hydrazine hydrate, producing 17α-hydrazinyl-3β,16α-dihydroxy-17β-(1H-pyrazolyl-3-yl)androst-5-ene that was used in reactions with aromatic aldehydes, leading to 17hydrazones. The treatment of 17β-[3-(dimethylamino)acryloyl]-16α,17α-epoxy-3β-hydroxyandrost-5-ene with phenylhydrazine led to the formation of 3β,16α-dihydroxy-17-(1-phenyl-1H-pyrazol-5-yl)androst-5-ene. At the same time, the reactions of epoxyandrostene with methylhydrazine or benzylamine proceeded with conservation of the epoxide ring and led to the formation of 16α,17-epoxyandrostanes containing a 1-methyl-1H-pyrazol-5-yl or 3-(benzylamino)acryloyl substituent at the position 17, respectively. The obtained hydrazones exhibited a moderate antiproliferative activity against the MCF-7 breast cancer cell line. The strongest antiproliferative potential was identified in the case of 17α-[(4-bromobenzylidene)hydrazinyl]-3β,16α-dihydroxy-17β-(1H-pyrazol-3-yl)androst-5-ene with an IC50 value around 16 μM.
