105246-18-2Relevant academic research and scientific papers
Synthesis and evaluation of 2′-substituted 4-(4′-carboxy- or 4′-carboxymethylbenzylidene)-N-acylpiperidines: Highly potent and in vivo active steroid 5α-reductase type 2 inhibitors
Picard, Franck,Barassin, Stephan,Mokhtarian, Armand,Hartmann, Rolf W.
, p. 3406 - 3417 (2007/10/03)
Sixteen compounds derived from N-acyl-4-benzylidenepiperidine-4′-carboxylic acids were synthesized and evaluated for inhibition of rat and human steroid 5α-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 (IC50 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.
(Pyridylcyanomethyl)piperazines as orally active PAF antagonists
Carceller,Almansa,Merlos,Giral,Bartroli,Garcia-Rafanell,Forn
, p. 4118 - 4134 (2007/10/02)
A series of (pyridylcyanomethyl)piperazines was prepared and evaluated for PAF-antagonist activity. Compounds were tested in vitro in a PAF-induced platelet aggregation assay and in vivo in a PAF-induced hypotension test in normotensive rats. Oral activity was ascertained through a PAF-induced mortality test in mice. The main structure-activity trends of the series were established. Activity was mainly found in four skeletons: 1-acyl-4-(3- pyridylcyanomethyl)-piperazine, 1-acyl-4-(4-pyridylcyanomethyl)piperazine, 1- acyl-4-(3-pyridylcyanomethyl)piperidine, and 1-acyl-4-cyano-4-(3- pyridylamino)piperidine. The acyl substituents, diphenylacetyl and 3,3- diphenylpropionyl, provided the most active compounds, and the introduction of an amine or hydroxy group in the 3,3-diphenylpropionyl substituent led to further improvement in oral activity. As a result, three of the most active compounds (100, 114, and 115) have been selected for further pharmacological development.
