Antihypertensive pyridylguanidine compounds

subject:Antihypertensive pyridylguanidine compounds
Chemical Structure:
Title:Petersen, H.J. (Leo Pharmaceutical Products Ltd. A/S)
Source:DE 2557438; FR 2294703; GB 1489879; JP 51086474; US 4057636

Drug Preparation:
This compound can be obtained in two related ways:1) By reaction of N-(4-pyridyl)-N'-(1,2,2-trimethylpropyl)thiourea (I) with cyanamide (II) by means of dicyclohexylcarbodiimide (DCC) and ethyldiisopropylamine in ether.2) The reaction of (I) with phosgene in toluene - THF by means of ethyldiisopropylamine in THF gives N-(4-pyridyl)-N'-(1,2,2-trimethylpropyl)carbodiimide (III), which is condensed with (II) by means of ethyldiisopropylamine.

Drug Preparation:
Thiourea (III) was prepared by condensation of 3-pyridyl isothiocyanate (I) with 1,1-dimethylpropyl amine (II). Desulfuration of thiourea (III) by means of phosgene and diisopropyl ethylamine, or triphenylphosphine and CCl4 gave rise to the carbodiimide (IV). Finally, addition of cyanamide to carbodiimide (IV) furnished the target N-cyanoguanidine derivative
References:No.49281
Title:P-1134
author:Blancafort, P.; Castaņer, J.; Serradell, M.N.; Hopkins, S.J.
Source:Drugs Fut 1981,6(3),149

Drug Preparation:
This compound can be obtained in two related ways:1) By reaction of N-(4-pyridyl)-N'-(1,2,2-trimethylpropyl)thiourea (I) with cyanamide (II) by means of dicyclohexylcarbodiimide (DCC) and ethyldiisopropylamine in ether.2) The reaction of (I) with phosgene in toluene - THF by means of ethyldiisopropylamine in THF gives N-(4-pyridyl)-N'-(1,2,2-trimethylpropyl)carbodiimide (III), which is condensed with (II) by means of ethyldiisopropylamine.