Dehydro Keto Methylene and Keto Methylene Analogues of Substance P. Synthesis and Biological Activity

Ariel Ewenson; Ralph Laufer; Michael Chorev; Zvi Selinger; Chaim Gilon

doi:10.1021/jm00397a026

Dehydro Keto Methylene and Keto Methylene Analogues of Substance P. Synthesis and Biological Activity

Ariel Ewenson
, Ralph Laufer
, Michael Chorev
, Zvi Selinger
, Chaim Gilon

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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: [p^Glu⁶,Gly⁹ᛘ(COCH₂)(Rs)Leu₁₀]SP_6-11 (4) and [pGlu₆,-(Rs)Phe⁷ᛘ(COCH₂)CRS)Phe⁸]SP_6-11(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]SP_6-11 (26) and the tetrapeptide analogue [pGlu⁶,(RS)Phe⁸ᛘ(COCH₂)Gly⁹]SP_6-9(-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
Pages (from-to)	416-421
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	31
Issue number	2
DOIs	https://doi.org/10.1021/jm00397a026
State	Published - 1 Feb 1988

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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,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.",

author = "Ariel Ewenson and Ralph Laufer and Michael Chorev and Zvi Selinger and Chaim Gilon",

year = "1988",

month = feb,

day = "1",

doi = "10.1021/jm00397a026",

language = "אנגלית",

volume = "31",

pages = "416--421",

journal = "Journal of Medicinal Chemistry",

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T1 - Dehydro Keto Methylene and Keto Methylene Analogues of Substance P. Synthesis and Biological Activity

AU - Ewenson, Ariel

AU - Laufer, Ralph

AU - Chorev, Michael

AU - Selinger, Zvi

AU - Gilon, Chaim

PY - 1988/2/1

Y1 - 1988/2/1

N2 - 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.

AB - 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.

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AN - SCOPUS:0009021370

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VL - 31

SP - 416

EP - 421

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 2

ER -

Dehydro Keto Methylene and Keto Methylene Analogues of Substance P. Synthesis and Biological Activity

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