Your browser doesn't support javascript.
loading
Cyanoamidines. II. Synthesis and pharmacological activity of N-arylalkyl-N'-cyano-3-pyridinecarboxamidines.
Nakajima, T; Nakajima, S; Izawa, T; Kashiwabara, T; Munezuka, Y.
Afiliação
  • Nakajima T; Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Chem Pharm Bull (Tokyo) ; 42(12): 2483-90, 1994 Dec.
Article em En | MEDLINE | ID: mdl-7697763
A new series of cyanoamidines, N-arylalkyl-N'-cyano-3-pyridinecarboxamidines was synthesized and evaluated for inhibitory effects on 40 mM KCl-induced contraction and norepinephrine (NE)-induced contraction of rat aorta strips. The N-phenethyl cyanoamidine 4c showed potent vasodilatory action. Further in vitro screening program using 4c as a lead compound resulted in the discovery of highly potent N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine (5j). Compound 5j induced the greatest increase in 86Rb+ efflux among cyanoamidine series. Subsequent modification of the pyridine ring of 5j was performed with evaluation for intravenous and oral antihypertensive activities. Introduction of an amino group at the 5-position of the pyridine ring furnished the new potassium channel opener, 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine+ ++ (9e; KRN4884), which showed highly potent antihypertensive activity and a long duration of antihypertensive action after oral administration. KRN4884 is under further development as an antihypertensive agent.
Assuntos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Vasodilatadores / Amidinas Limite: Animals Idioma: En Revista: Chem Pharm Bull (Tokyo) Ano de publicação: 1994 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridinas / Vasodilatadores / Amidinas Limite: Animals Idioma: En Revista: Chem Pharm Bull (Tokyo) Ano de publicação: 1994 Tipo de documento: Article