Ewenson A, Laufer R, Chorev M, Selinger Z, Gilon C
Department of Organic, Chemistry, Hebrew University of Jerusalem, Israel.
J Med Chem. 1988 Feb;31(2):416-21. doi: 10.1021/jm00397a026.
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.
描述了使用经典肽合成法合成P物质的脱氢亚甲基酮和亚甲基酮类似物。制备了以下类似物：[pGlu6，Gly9psi(COCH2)(RS)Leu10]SP6-11(4)和[pGlu6，-(RS)Phe7 psi(COCH2)(RS)Phe8]SP6-11(8)。采用改进的脱保护方案，使用米尔温试剂(Et3OBF4)使得新型脱氢亚甲基酮类似物[pGlu6，(RS)Phe7 psi-(COCH2)δ(E)Phe8]SP6-11(26)和四肽类似物[pGlu6，(RS)Phe8 psi(COCH2)Gly9]SP6-9(-OMe)(23)的合成成为可能。化合物4在引发豚鼠回肠收缩方面是一种弱激动剂。化合物26是大鼠下丘脑制剂中P物质降解的有效抑制剂，IC50值为1.8 microM。
