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,Gly9ᛘ(COCH2)(Rs)Leu10]SP6-11 (4) and [pGlu6,-(Rs)Phe7ᛘ(COCH2)CRS)Phe8]SP6-11(8). The use of an improved deprotection scheme employing Meerwein's reagent (Et3 OBF4) made possible the syntheses of the novel dehydro keto methylene analogue [pGlu6,(Rs)Phe7ᛘ(COCH2)Δ(E)Phe8]SP6-11 (26) and the tetrapeptide analogue [pGlu6,(RS)Phe8ᛘ(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 μM.
Original language | English |
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Pages (from-to) | 416-421 |
Number of pages | 6 |
Journal | Journal of Medicinal Chemistry |
Volume | 31 |
Issue number | 2 |
DOIs | |
State | Published - 1 Feb 1988 |