Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a series of 4-hydroxyphenyl ketones as potential inhibitors of 17[beta]-hydroxysteroid dehydrogenase type 3 (17[beta]-HSD3)

Lota, Rupinder K., Dhanani, Sachin, Owen, Caroline P. and Ahmed, Sabbir (2006) Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a series of 4-hydroxyphenyl ketones as potential inhibitors of 17[beta]-hydroxysteroid dehydrogenase type 3 (17[beta]-HSD3). Bioorganic & Medicinal Chemistry Letters, 16(17), pp. 4519-4522. ISSN (print) 0960-894X

Official URL: http://dx.doi.org/10.1016/j.bmcl.2006.06.029

Abstract

We report the preliminary results of the synthesis and biochemical evaluation of a number of 4-hydroxyphenyl ketones as inhibitors of the isozyme of the enzyme 17beta-hydroxysteroid dehydrogenase (17beta-HSD) responsible for the conversion of androstenedione (AD) to testosterone (T), more specifically type 3 (17beta-HSD3). The results of our study suggest that we have synthesised compounds which are, in general, potent inhibitors of 17beta-HSD3, in particular, we discovered that 1-(4-hydroxy-phenyl)-nonan-1-one (8) was the most potent (IC(50) = 2.86 +/- 0.03 microM). We have therefore provided good lead compounds in the synthesis of novel non-steroidal inhibitors of 17beta-HSD3.

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