Synthesis of arginine-vasopressins, modified in positions 1 and 2, as antagonists of the vasopressor response to the parent hormone.
In an attempt to determine some of the structural features in position 1 that account for antivasopressor activity, eight new 1-(beta, beta-dialkyl-substituted) analogues of 1-(3-mercaptopropanoic acid)-8-arginine-vasopressin and 1-(3-mercaptopropanoic acid)-2-O-methyltyrosine-8-arginine-vasopressin have been designed and synthesized. The protected precursors required for these peptides were obtained by a combination of solid-phase and solutions methods. Some of the reported analogues, namely 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine-vasopressin, 1-(1-mercapto-4-methylcyclohexaneacetic acid)-2-O-methyltryosine-8-arginine-vasopressin, 1-(4-tert-butyl-1-mercaptocyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine- vasopressin, 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-8-arginine-vasopressin and 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-2-O-methyltyrosine-8-arginine- vasopressin, are among the most potent and selective antagonists of the vasopressor response to arginine-vasopressin reported to date.
Lammek
B
B
Institute of Chemistry, University of Gdańsk, Poland.
Rekowski
P
P
Kupryszewski
G
G
Melin
P
P
Ragnarsson
U
U
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains
D001127:Arginine Vasopressin