Collect. Czech. Chem. Commun. 1989, 54, 1966-1978

Potential antidepressants: 2-(Aminoalkoxy)biphenyls and some related ω-substituted 2-alkoxybiphenyls

Irena Červená, Jiří Holubek, Emil Svátek, Jan Metyš and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Reactions of 2-hydroxybiphenyl with α,ω-dibromoalkanes gave the 2-(bromoalkoxy)biphenyls IIIa-IIId. The 2-(dimethylaminoalkoxy)biphenyls VIa and VIb were transformed via carbamates VIIa and VIIb to the secondary amines Va and Vb. Their homologues Vc and Vd were obtained from the bromo compounds IIIc and IIId by treatment with methylamine. Bromo compounds IIIa and IIIb were reacted with 1-methylpiperazine, 2-(1-piperazinyl)ethanol, 3-(1-piperazinyl)propanol, and 4-amino-1-benzylpiperidine and gave the diamines VIIIa, VIIIb, IXa, Xa, Xb, and XIa. Addition of 2-hydroxybiphenyl to acrylonitrile afforded the nitrile XIIa. The homologous nitrile XIIb was obtained from the bromo compound IIIb and sodium cyanide in dimethyl sulfoxide. Nitriles XIIa and XIIb were reduced with aluminium hydride to diamines IVb and IVc. The nitriles were also transformed to hydrochlorides of the corresponding ethyl imidates XIVa and XIVb. Their hydrolysis resulted in the esters XVa and XVb. The acid XIIIa was obtained by acid hydrolysis of the nitrile XIIa; the acid XIIIb resulted from the acid hydrolysis of the ester XVb. The imidate XIVb was transformed to the amidine XVIb and to the dihydroimidazole XVIIb. Only the amine Vc showed properties indicative of potential antidepressant.