Highly potent 1-aminocyclohexane-1-carboxylic acid substituted V2 agonists of arginine vasopressin.
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.
Kowalczyk
Wioleta
W
Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. wiola@chem.univ.gda.pl
Prahl
Adam
A
Derdowska
Izabela
I
Dawidowska
Olga
O
Slaninová
Jirina
J
Lammek
Bernard
B
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
D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; D004232:Diuretics; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C014966:1-aminocyclohexanecarboxylic acid