173604-55-2Relevant academic research and scientific papers
Novel substituted piperidines, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof
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Page 23, (2008/06/13)
The present invention relates to substituted piperidines of general formula wherein R, R2 to R5, A, X, Z and n are defined as in claim 1, the tautomers, diastereomers, enantiomers, mixtures and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly CGRP-antagonistic properties, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof.
Design, synthesis, and structure-activity relationship studies of novel 1-[(1-acyl-4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine derivatives as potent, orally active platelet-activating factor antagonists
Carceller, Elena,Merlos, Manuel,Giral, Marta,Balsa, Dolors,García-Rafanell, Julián,Forn, Javier
, p. 487 - 493 (2007/10/03)
Replacement of the polar head of our previous series of 1-acyl-4-[(2-methyl-3-pyridyl)-cyanomethyl]piperazines with a 2-methylimidazo[4,5-c]pyridine group has led to the identification of a new series of 1-[(1-acyl-4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine derivatives as potent, orally active platelet-activating factor (PAF) antagonists. On the basis of the general structure - activity relationship trends found for the acyl substituent in our earlier series, five groups of compounds were tested, diaryl- or alkylarylpropanoyl derivatives, their 3-hydroxy-substituted analogues, and urea, carbamate and amino acid derivatives. The optimal compound 19 (UR-12670), bearing the 3,3-diphenylpropanoyl moiety, exhibited very high in vitro and in vivo potency (IC50 = 0.0076 μM for the in vitro PAF-induced platelet aggregation assay, ID50 = 0.0086 mg/kg for the in vivo PAF-induced hypotension test in normotensive rats, and ID50 = 0.092 mg/kg po and 0.0008 mg/kg iv for the PAF-induced mortality test in mice). Compound 19 also showed long duration of activity. It gave 100% protection against PAF-induced mortality in mice 7 h after iv administration of a single dose of 1 mg/kg and also provided 100% inhibition of PAF-induced aggregation in dog whole blood 6 h after iv administration of the same dose. The lead structure 19 has been selected for in-depth pharmacological evaluation.
