1475-05-4Relevant academic research and scientific papers
Pharmacological profile of a novel series of NK1, antagonists. In vitro and in vivo potency of benzimidazolone derivatives
Remond,Portevin,Bonnet,Canet,Regoli,De Nanteuil
, p. 843 - 868 (2007/10/03)
By low throughput examination of our chemical library, compound 7 was selected as a lead NK1, antagonist with a K(i) of 7.1 nM. Modifications of its structure led to the finding that the in vitro potency could be markedly enhanced by disubstituting the anilino phenyl ring as in compounds 13 or 22. Human binding data correlated rather well with results obtained with in vitro animal smooth muscle preparations. Several agents proved to possess antinociceptive properties as exemplified in the hot-plate test in mice; compound 13 was the most active with ED50 of 0.001 and 0.3 mg/kg after iv and po administration respectively. Furthermore, antagonist 71 was found to be a potent inhibitor of SP-induced bronchoconstriction in guinea-pigs with an ED50 between 0.1 and 0.03 mg/kg iv. Furthermore, upon oral administration, 71 was observed to be active in a model of SP-induced bronchial hypersensitivity in mice, with an ID50 of around 3 mg/kg.
Piperidine compounds
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, (2008/06/13)
The invention relates to the compounds of formula (I): STR1 in which: R1 represents alkyl, phenyl, naphthyl, pyridyl or thienyl group, each phenyl, naphthyl, pyridyl or thienyl optionally being substituted, R2 represents a hydrogen atom or a substituted or unsubstituted alkyl, substituted or unsubstituted phenyl, cycloalkyl, piperidino or substituted or unsubstituted amino group, X represents CO or SO2, R3 represents hydrogen or alkyl, R4 represents alkyl, substituted or unsubstituted phenyl or trihalomethyl, or else R3 and R4 form, together with the carbon atoms which carry them, cyclo(C3 -C7)alkenyl, A represents phenyl, naphthyl or pyridyl ring, each phenyl, naphthyl or pyridyl ring optionally being substituted, their isomers, the corresponding quaternary ammonium salts of the piperidine and their addition salts with a pharmaceutically acceptable acid, an medicinal products containing the same are useful as antagonists of NK1 receptors.
