Substituted androstanes as aromatase inhibitors

Abstract

The synthesis and structure ± activity relationships of inhibitors of steroid aromatase which catalyses the last stage of a multistep biotransformation of cholesterol into estrogens, viz., aromatisation of C 19 -steroids into C 18 -phenolic steroids, are discussed. Compounds of the androstane series which are structurally related to the natural substrate, viz., androst-4-ene-3,17dione, are the subjects of consideration. The review encompasses problems of synthesis of various substituted androstanes and their aromatase-inhibiting activities and structural requirements for selective specific aromatase inhibitors based on in vitro and in vivo structure ± activity studies of compounds synthesised, their biological properties and the results of clinical trials. Special attention is paid to practical applications of aromatase inhibitors in the treatment of hormone-dependent mammary and ovarian tumours as well as benign prostatic tumours. In writing this report, the author has used all the information currently available in the chemical, biochemical, endocrinological and medicinal literature as well as in patents. The bibliography includes 173 references.

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“…Preparation of 23 is described in the Supporting Information, according to a previous report. 31 Androsta-4,6-diene-3,17-dione (24). Preparation of 24 was performed by adapting a described strategy.…”

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An amperometric immunosensor based on nanobiocomposite materials for the determination of alpha-phetoprotein in serum

“…Chem 3, 310. Chem 53, 2026 doi:10.1016/j.jbiotec.2010.09.020 Keywords: 1-dehygrogenation; bioconversion; Mannich steroid bases; 6-(N-methyl-N-phenylaminomethyl)-androst-4-ene-3,17dione N,N-Disubstituted aminomethylene androstanes, the so called Mannich steroid bases, -are the important structural precursors in the chemical synthesis of 6-methylene-and 6␣-methyl-steroids, as well as the perspective substances for the production of novel medical preparations which combine biological activity of the parent compound and potency of the amine constituent (Levina., 1998). J Proteom 71, 265.…”