N-（6-官能化氨基-3-吡啶基）-N'-双环烷基-N''-氰基胍类作为抗高血压药物的合成与药理评价

Synthesis and pharmacological evaluation of N-(6-functionalized-amino-3-pyridyl)-N'-bicycloalkyl-N''-cyanoguanidine s as antihypertensive agents.

作者信息

Eda M, Takemoto T, Okada T, Sakashita H, Matzno S, Gohda M, Hayashi K, Nakamura N, Fukaya C

机构信息

Research Division, Green Cross Corporation, Osaka, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1996 Feb;44(2):307-13. doi: 10.1248/cpb.44.307.

DOI:10.1248/cpb.44.307

PMID:8998837

Abstract

A series of amino acid conjugates of N-(6-amino-3-pyridyl)-N'-[exo-bicyclo[2.2.1]hept-2-yl]-N''- cyanoguanidine (4) were prepared and evaluated as antihypertensive agents. The parent compound 4 showed potent potassium channel-opening and antihypertensive activities, but with undesirable changes of the urinary balance of electrolytes. However, alanine and histidine congeners (9,19) reduced this undesirable side effect of 4 through improved pharmacokinetics without loss of antihypertensive activity. They also provided additional information on the structural requirements for pinacidil-type potassium channel openers.

摘要

制备了一系列N-(6-氨基-3-吡啶基)-N'-[外向双环[2.2.1]庚-2-基]-N''-氰基胍(4)的氨基酸缀合物，并将其作为抗高血压药物进行评估。母体化合物4显示出强效的钾通道开放和抗高血压活性，但伴有电解质尿平衡的不良变化。然而，丙氨酸和组氨酸类似物(9,19)通过改善药代动力学减少了4的这种不良副作用，而不丧失抗高血压活性。它们还提供了关于匹那地尔型钾通道开放剂结构要求的更多信息。