Synthesis and some pharmacological properties of two new antagonists of oxytocin.
Two new 1-beta,beta-disubstituted analogues of [1-deamino]-oxytocin dOT: [1'-(1'-thio-4'-methylcyclohexane)-acetic acid1]-oxytocin (MeCAOT), and [1'-(1'-methyl-4'-thiopiperidine)-acetic acid1]-oxytocin (MePAOT), were synthesized to determine some of the structural features that account for antioxytocic potency. The protected precursors required for these analogues were synthesized by a combination of solid phase and 8 + 1 couplings in solution. MeCAOT is an effective antagonist of oxytocic response to oxytocin (pA2 = 7.3).
Institute of Chemistry, University of Gdańsk, Poland.
P
P
Rekowski
P
P
Melin
B
B
Lammek
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects
C055082:oxytocin, 1'-(1'-thio-4'-methylcyclohexane)acetic acid-; C055080:oxytocin, 1'-(1'-methyl-4'-thiopiperidine)acetic acid-; D010121:Oxytocin