Dipeptidyl α-fluorovinyl Michael acceptors: Synthesis and activity against cysteine proteases

Koen Steert; Ibrahim El-Sayed; Pieter Van der Veken; Alisa Krishtal; Christian Van Alsenoy; Gareth D. Westrop; Jeremy C. Mottram; Graham H. Coombs; Koen Augustyns; Achiel Haemers

doi:10.1016/j.bmcl.2007.09.075

Dipeptidyl α-fluorovinyl Michael acceptors: Synthesis and activity against cysteine proteases

Koen Steert
, Ibrahim El-Sayed
, Pieter Van der Veken
, Alisa Krishtal
, Christian Van Alsenoy
, Gareth D. Westrop
, Jeremy C. Mottram
, Graham H. Coombs
, Koen Augustyns
, Achiel Haemers

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

35 Scopus citations

Abstract

The synthesis of novel dipeptidyl α-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8ΔCTE) revealed low biological activity. Relative rates of Michael additions of 2′-(phenethyl)thiol with vinyl sulfone and α-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.

Original language	English (US)
Pages (from-to)	6563-6566
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2007.09.075
State	Published - Dec 1 2007
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Keywords

Cysteine proteases
Inhibitors
α-Fluorovinyl Michael acceptors

Access to Document

10.1016/j.bmcl.2007.09.075

Cite this

@article{930035bf2f9841669203ec6d4040301e,

title = "Dipeptidyl α-fluorovinyl Michael acceptors: Synthesis and activity against cysteine proteases",

abstract = "The synthesis of novel dipeptidyl α-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8ΔCTE) revealed low biological activity. Relative rates of Michael additions of 2′-(phenethyl)thiol with vinyl sulfone and α-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.",

keywords = "Cysteine proteases, Inhibitors, α-Fluorovinyl Michael acceptors",

author = "Koen Steert and Ibrahim El-Sayed and \{Van der Veken\}, Pieter and Alisa Krishtal and \{Van Alsenoy\}, Christian and Westrop, \{Gareth D.\} and Mottram, \{Jeremy C.\} and Coombs, \{Graham H.\} and Koen Augustyns and Achiel Haemers",

note = "Funding Information: We are indebted to the Flemish Fund for Scientific Research (FWO-Vlaanderen) for financial support. ",

year = "2007",

month = dec,

day = "1",

doi = "10.1016/j.bmcl.2007.09.075",

language = "English (US)",

volume = "17",

pages = "6563--6566",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "23",

}

TY - JOUR

T1 - Dipeptidyl α-fluorovinyl Michael acceptors

T2 - Synthesis and activity against cysteine proteases

AU - Steert, Koen

AU - El-Sayed, Ibrahim

AU - Van der Veken, Pieter

AU - Krishtal, Alisa

AU - Van Alsenoy, Christian

AU - Westrop, Gareth D.

AU - Mottram, Jeremy C.

AU - Coombs, Graham H.

AU - Augustyns, Koen

AU - Haemers, Achiel

N1 - Funding Information: We are indebted to the Flemish Fund for Scientific Research (FWO-Vlaanderen) for financial support.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - The synthesis of novel dipeptidyl α-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8ΔCTE) revealed low biological activity. Relative rates of Michael additions of 2′-(phenethyl)thiol with vinyl sulfone and α-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.

AB - The synthesis of novel dipeptidyl α-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8ΔCTE) revealed low biological activity. Relative rates of Michael additions of 2′-(phenethyl)thiol with vinyl sulfone and α-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.

KW - Cysteine proteases

KW - Inhibitors

KW - α-Fluorovinyl Michael acceptors

UR - https://www.scopus.com/pages/publications/35648952198

UR - https://www.scopus.com/pages/publications/35648952198#tab=citedBy

U2 - 10.1016/j.bmcl.2007.09.075

DO - 10.1016/j.bmcl.2007.09.075

M3 - Article

C2 - 17936625

AN - SCOPUS:35648952198

SN - 0960-894X

VL - 17

SP - 6563

EP - 6566

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

Dipeptidyl α-fluorovinyl Michael acceptors: Synthesis and activity against cysteine proteases

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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