Isosteric exchange of the acylsulfonamide moiety in Abbott's Bcl-X(L) protein interaction antagonist

Alexander Doemling; Walfrido Antuch; Barbara Beck; Vesna Schauer-Vukasinovic

doi:10.1016/j.bmcl.2008.05.096

Isosteric exchange of the acylsulfonamide moiety in Abbott's Bcl-X(L) protein interaction antagonist

Alexander Doemling^*, Walfrido Antuch, Barbara Beck, Vesna Schauer-Vukasinovic

^*Corresponding author for this work

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

9 Citations (Scopus)

Abstract

A multi-component reaction strategy was used for the fast and efficient synthesis of amide isosteres of known Bcl-2 inhibitors capable of disrupting protein-protein interactions. Ugi reaction and a subsequent nucleophilic aromatic substitution reaction provide a versatile path to libraries of compounds similar to Abbott's acylsulfonamides. Modeling arguments are used to explain the inferior activity of the amide as opposed to the sulfonamide series. (c) 2008 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	4115-4117
Number of pages	3
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	18
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2008.05.096
Publication status	Published - 15-Jul-2008
Externally published	Yes

Keywords

multi-component reaction
protein-protein interaction
Bcl
cancer
apoptosis
isocyanide
structure-based design
PARALLEL SYNTHESIS
INHIBITOR
BCL-X(L)
DESIGN

Access to Document

10.1016/j.bmcl.2008.05.096

Cite this

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title = "Isosteric exchange of the acylsulfonamide moiety in Abbott's Bcl-X(L) protein interaction antagonist",

abstract = "A multi-component reaction strategy was used for the fast and efficient synthesis of amide isosteres of known Bcl-2 inhibitors capable of disrupting protein-protein interactions. Ugi reaction and a subsequent nucleophilic aromatic substitution reaction provide a versatile path to libraries of compounds similar to Abbott's acylsulfonamides. Modeling arguments are used to explain the inferior activity of the amide as opposed to the sulfonamide series. (c) 2008 Elsevier Ltd. All rights reserved.",

keywords = "multi-component reaction, protein-protein interaction, Bcl, cancer, apoptosis, isocyanide, structure-based design, PARALLEL SYNTHESIS, INHIBITOR, BCL-X(L), DESIGN",

author = "Alexander Doemling and Walfrido Antuch and Barbara Beck and Vesna Schauer-Vukasinovic",

year = "2008",

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doi = "10.1016/j.bmcl.2008.05.096",

language = "English",

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pages = "4115--4117",

journal = "Bioorganic & Medicinal Chemistry Letters",

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publisher = "American Chemical Society",

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TY - JOUR

T1 - Isosteric exchange of the acylsulfonamide moiety in Abbott's Bcl-X(L) protein interaction antagonist

AU - Doemling, Alexander

AU - Antuch, Walfrido

AU - Beck, Barbara

AU - Schauer-Vukasinovic, Vesna

PY - 2008/7/15

Y1 - 2008/7/15

N2 - A multi-component reaction strategy was used for the fast and efficient synthesis of amide isosteres of known Bcl-2 inhibitors capable of disrupting protein-protein interactions. Ugi reaction and a subsequent nucleophilic aromatic substitution reaction provide a versatile path to libraries of compounds similar to Abbott's acylsulfonamides. Modeling arguments are used to explain the inferior activity of the amide as opposed to the sulfonamide series. (c) 2008 Elsevier Ltd. All rights reserved.

AB - A multi-component reaction strategy was used for the fast and efficient synthesis of amide isosteres of known Bcl-2 inhibitors capable of disrupting protein-protein interactions. Ugi reaction and a subsequent nucleophilic aromatic substitution reaction provide a versatile path to libraries of compounds similar to Abbott's acylsulfonamides. Modeling arguments are used to explain the inferior activity of the amide as opposed to the sulfonamide series. (c) 2008 Elsevier Ltd. All rights reserved.

KW - multi-component reaction

KW - protein-protein interaction

KW - Bcl

KW - cancer

KW - apoptosis

KW - isocyanide

KW - structure-based design

KW - PARALLEL SYNTHESIS

KW - INHIBITOR

KW - BCL-X(L)

KW - DESIGN

U2 - 10.1016/j.bmcl.2008.05.096

DO - 10.1016/j.bmcl.2008.05.096

M3 - Article

VL - 18

SP - 4115

EP - 4117

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 14

ER -