title: Synthesis and pharmacological evaluation of N-(6-functionalized-amino-3-pyridyl)-N'-bicycloalkyl-N''-cyanoguanidine s as antihypertensive agents.
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.
authors.affiliation: Research Division, Green Cross Corporation, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Eda
authors.forename: T
authors.initials: T
authors.lastname: Takemoto
authors.forename: T
authors.initials: T
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Sakashita
authors.forename: S
authors.initials: S
authors.lastname: Matzno
authors.forename: M
authors.initials: M
authors.lastname: Gohda
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
authors.forename: C
authors.initials: C
authors.lastname: Fukaya
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004232:Diuretics / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020110:Pinacidil; D011169:Portal Vein / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil