title: Highly potent 1-aminocyclohexane-1-carboxylic acid substituted V2 agonists of arginine vasopressin.
abstract: The synthesis and some pharmacological properties of two sets of analogues, one consisting of six peptides with 1-aminocyclohexane-1-carboxylic acid (Acc) in position 2 and the other with the amino acid in position 3, have been described. All the peptides were tested for their pressor, antidiuretic, and uterotonic in vitro activities. The Acc(2) modification has been shown to selectively modulate the activities of the analogues. Four of the compounds were highly potent antidiuretic agonists with different pressor and uterotonic activities. On the other hand, the 3-substituted counterparts failed to exhibit any of the activities. One exception was provided by the [Mpa(1),Acc(3),Val(4),D-Arg(8)]VP analogue, which exhibited antidiuretic activity matching that of AVP, yet, unlike AVP, it was fairly selective.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. wiola@chem.univ.gda.pl
authors.forename: Wioleta
authors.initials: W
authors.lastname: Kowalczyk
authors.forename: Adam
authors.initials: A
authors.lastname: Prahl
authors.forename: Izabela
authors.initials: I
authors.lastname: Derdowska
authors.forename: Olga
authors.initials: O
authors.lastname: Dawidowska
authors.forename: Jirina
authors.initials: J
authors.lastname: Slaninová
authors.forename: Bernard
authors.initials: B
authors.lastname: Lammek
mesh_terms: D000598:Amino Acids, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists*; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; D004232:Diuretics; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C014966:1-aminocyclohexanecarboxylic acid