Francois Montavon

Piperidine-renin inhibitors compounds with improved physicochemical properties

Piperidine renin inhibitors with heterocyclic core modifications or hydrophilic attachments show improved physical properties (lower lipophilicity, improved solubility). Tetrahydroquinoline derivative rac-30 with a molecular weight of 517 and a log D(pH 7.4) of 1.9 displays potent and long lasting blood pressure lowering effects after oral administration to sodium depleted conscious marmosets.

Carbohydrate α-oxoketene N,O-ketals in the synthesis of dihydroquinolines

The carbohydrate nitro enone 1 was found to react with amines to give α-ketene ketals; the formation of carbohydrate azo derivatives could be suppressed by addition of an electron-rich aniline quenching agent. Upon reaction with benzaldehyde in the presence of trifluoroacetic acid, the α-oxoketene ketals afforded dihydroquinolines in a cyclization reaction forming two new carbon–carbon bonds. For the dihydroquinoline 18 the newly formed stereocenter was ascertained by X-ray crystallography. The two-step reaction could be carried out as one multicomponent reaction. Electron-poor anilines led to Hantzsch-type products incorporating two enaminone molecules; the crystal structure of representative 30 is reported.