Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5alpha-reductase inhibitors: a legitimate approach.

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Aggarwal S, Thareja S, Bhardwaj TR, Haupenthal J, Hartmann RW, Kumar M

Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5alpha-reductase inhibitors: a legitimate approach.

Eur J Med Chem. 2012 Aug;54:728-39. doi: 10.1016/j.ejmech.2012.06.026. Epub 2012 Jun 21.

PubMed ID

22776417 [ View in PubMed

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Abstract

In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5alpha-reductase inhibitory activity by measuring the conversion of [(3)H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5alpha-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5alpha-reductase II enzyme with IC(50) values of 54.1 +/- 9.5, 22.1 +/- 2.4, 72.8 +/- 2.3 and 26.5 +/- 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Finasteride	3-oxo-5-alpha-steroid 4-dehydrogenase 1	IC 50 (nM)	453	N/A	N/A	Details
Finasteride	3-oxo-5-alpha-steroid 4-dehydrogenase 2	IC 50 (nM)	30.3	N/A	N/A	Details