Synthesis and Pharmacological Evaluation of N-(6-Functionalized-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidines as Antihypertensive Agents

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 chan...

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Bibliographic Details
Published inChemical & pharmaceutical bulletin Vol. 44; no. 2; pp. 307 - 313
Main Authors EDA, Masahiro, TAKEMOTO, Tadahiro, OKADA, Takehiro, SAKASHITA, Hiroshi, MATZNO, Sumio, GOHDA, Maki, HAYASHI, Kazutaka, NAKAMURA, Norifumi, FUKAYA, Chikara
Format Journal Article
LanguageEnglish
Published TOKYO The Pharmaceutical Society of Japan 1996
Pharmaceutical Soc Japan
Japan Science and Technology Agency
Subjects
antihypertensive agent
Chemistry
Chemistry, Medicinal
Chemistry, Multidisciplinary
functionalized congener approach
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Physical Sciences
potassium channel opener
Science & Technology
MECHANISM
antihypertensive agent
CATECHOLAMINES
functionalized congener approach
CROMAKALIM
POTASSIUM CHANNEL ACTIVATORS
AFFINITY
potassium channel opener
PINACIDIL-TYPE CYANOGUANIDINES
CONGENERS
RECEPTORS
OPENERS
NITROETHENEDIAMINES
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Summary: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. Howere, 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.
ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.44.307