title: 1-(2-aminoethyl)-6-aryl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepines with diuretic and natriuretic activity.
abstract: A series of 1-(2-amino-1-phenylethyl)-6-phenyl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared and evaluated for diuretic activity. These compounds have diuretic and natriuretic activity but no kaliuretic activity when evaluated by oral administration to the conscious rat. The structure requirements for this activity are discussed. In particular it was found that the 2-aminoethyl side chain at C-1 with hydrogen or methyl substituents on the amino group was required for diuretic activity. A substituent at C-8 was also required; soft substituents such as methylthio and iodo at this position favored activity. Compounds with both phenyl and 2-pyridyl substituents at C-6 were active; substituents on the C-6 phenyl, however, reduced or eliminated the activity. Substituents other than phenyl at the 1-position of the 2-aminoethyl side chain were detrimental to activity; phenyl substitution at this position was required for activity when the substituent at C-8 was chloro but not when it was bromo.
authors.affiliation: Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
authors.forename: J B
authors.initials: JB
authors.lastname: Hester
authors.forename: J H
authors.initials: JH
authors.lastname: Ludens
authors.forename: D E
authors.initials: DE
authors.lastname: Emmert
authors.forename: B E
authors.initials: BE
authors.lastname: West
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002712:Chlorides / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D015394:Molecular Structure; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D014230:Triazoles; D001569:Benzodiazepines; D011188:Potassium