Synthesis and evaluation of 2'-substituted 4-(4'-carboxy- or 4'-carboxymethylbenzylidene)-N-acylpiperidines: highly potent and in vivo active steroid 5alpha-reductase type 2 inhibitors.

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Picard F, Barassin S, Mokhtarian A, Hartmann RW

Synthesis and evaluation of 2'-substituted 4-(4'-carboxy- or 4'-carboxymethylbenzylidene)-N-acylpiperidines: highly potent and in vivo active steroid 5alpha-reductase type 2 inhibitors.

J Med Chem. 2002 Aug 1;45(16):3406-17.

PubMed ID

12139451 [ View in PubMed

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Abstract

Sixteen compounds derived from N-acyl-4-benzylidenepiperidine-4'-carboxylic acids were synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes types 1 and 2. In the dicyclohexylacetyl series, fluorination in the 2-position of the benzene nucleus (15), exchange of the carboxy group by a carboxymethyl moiety (20), and combination of both structural modifications (25) led to highly active inhibitors of the human type 2 isozyme (IC(50) values: 15, 11 nM; 20, 6 nM; 25, 7 nM; finasteride, 5 nM). In vivo all compounds tested markedly reduced the prostate weights in castrated testosterone-treated rats. Oral activity was shown for compound 7. From the finding that compound 15 is active in the rat, although it is a rather poor inhibitor of the rat enzyme and is a strong inhibitor of the human enzyme, it is concluded that it should be highly potent in men.

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)	41	N/A	N/A	Details
Finasteride	3-oxo-5-alpha-steroid 4-dehydrogenase 2	IC 50 (nM)	5	N/A	N/A	Details