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A new approach to the synthesis of 17-pyrazolylandrostane

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Chemistry of Heterocyclic Compounds Aims and scope

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 17-hydrazones. 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 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.

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Authors and Affiliations

  1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Ave., Moscow, 119991, Russia

    Alexander V. Komkov, Leonid G. Menchikov, Andrey S. Dmitrenok, Inna S. Levina & Igor V. Zavarzin

  2. Department of Experimental Tumor Biology, N. N. Blokhin National Medical Research Center of Oncology, 24, Build. 15 Kashirskoye Highway, Moscow, 115522, Russia

    Alexander M. Scherbakov & Diana I. Salnikova

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  1. Alexander V. Komkov
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  2. Leonid G. Menchikov
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Correspondence to Igor V. Zavarzin.

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Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2023, 59(8), 554–563

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Komkov, A.V., Menchikov, L.G., Dmitrenok, A.S. et al. A new approach to the synthesis of 17-pyrazolylandrostane. Chem Heterocycl Comp 59, 554–563 (2023). https://doi.org/10.1007/s10593-023-03233-8

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