Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates

Zwick, Vincent; Nurisso, Alessandra; Simoes Avello, Claudia; Bouchet, Samuel; Martinet, Nadine; Lehotzky, Attila; Ovadi, Judit; Cuendet, Muriel; Blanquart, Christophe; Bertrand, Philippe

doi:10.1016/j.bmcl.2015.11.011

Scientific article

English

Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates

ContributorsZwick, Vincent; Nurisso, Alessandra; Simoes Avello, Claudia; Bouchet, Samuel; Martinet, Nadine; Lehotzky, Attila; Ovadi, Judit; Cuendet, Muriel

; Blanquart, Christophe; Bertrand, Philippe

Published inBioorganic & medicinal chemistry letters, vol. 26, no. 1, p. 154-159

Publication date2016

Abstract

Conditions for the metathesis of alkenes in the convergent synthesis of HDAC inhibitors have been improved by continuous catalyst flow injection in the reaction media. Intermediate and target compounds obtained were tested for their ability to induce HDAC inhibition and tubulin acetylation, revealing the key role of the tert-butyloxycarbonyl (BOC) group for more HDAC6 selectivity. Molecular modelling added rationale for this BOC effect.

Keywords

Alkenes/chemistry
Benzamides/chemistry
Dose-Response Relationship
Drug
Formic Acid Esters/chemistry
Histone Deacetylase Inhibitors/chemistry/pharmacology
Histone Deacetylases/metabolism
Humans
Hydroxamic Acids/chemistry
Models
Molecular
Molecular Structure
Structure-Activity Relationship

Affiliation

Faculté des sciences / Section des sciences pharmaceutiques

Citation (ISO format)

ZWICK, Vincent et al. Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates. In: Bioorganic & medicinal chemistry letters, 2016, vol. 26, n° 1, p. 154–159. doi: 10.1016/j.bmcl.2015.11.011

Article (Published version)

Identifiers

PID : unige:94979
DOI : 10.1016/j.bmcl.2015.11.011
PMID : 26611919

ISSN of the journal0960-894X

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Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates

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