title: Dehydro keto methylene and keto methylene analogues of substance P. Synthesis and biological activity.
abstract: The synthesis of dehydro keto methylene and keto methylene analogues of substance P using classical peptide synthesis is described. The following analogues were prepared: [pGlu6,Gly9psi(COCH2)(RS)Leu10]SP6-11 (4) and [pGlu6,-(RS)Phe7 psi(COCH2)(RS)Phe8]SP6-11 (8). The use of an improved deprotection scheme employing Meerwein's reagent (Et3OBF4) made possible the syntheses of the novel dehydro keto methylene analogue [pGlu6,(RS)Phe7 psi-(COCH2)delta(E)Phe8]SP6-11 (26) adn the tetrapeptide analogue [pGlu6,(RS)Phe8 psi(COCH2)Gly9]SP6-9(-OMe) (23). Compound 4 was a weak agonist in provoking contractions of the guinea pig ileum. Compound 26 was a potent inhibitor of SP degradation in rat hypothalamus preparations, with an IC50 value of 1.8 microM.
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D008297:Male; D051381:Rats; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P