Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2

Marie Grimstrup, Øystein Rist, Jean-Marie Receveur, Thomas M Frimurer, Trond Ulven, Jesper M Mathiesen, Evi Kostenis, Thomas Högberg

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2010-Feb-1
OriginalsprogEngelsk
TidsskriftBioorganic & Medicinal Chemistry Letters
Vol/bind20
Udgave nummer3
Sider (fra-til)1181-5
Antal sider4
ISSN0960-894X
DOI
StatusUdgivet - 1. feb. 2010

Fingeraftryk

Thiazoles
Computer Simulation
Formyl Peptide Receptor
Th2 Cells
Acids
Molecules

Bibliografisk note

Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Citer dette

Grimstrup, Marie ; Rist, Øystein ; Receveur, Jean-Marie ; Frimurer, Thomas M ; Ulven, Trond ; Mathiesen, Jesper M ; Kostenis, Evi ; Högberg, Thomas. / Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2. I: Bioorganic & Medicinal Chemistry Letters. 2010 ; Bind 20, Nr. 3. s. 1181-5.
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title = "Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2",
abstract = "Structure-activity relationships have been established by exploring the eastern and western side of 5-thiazolyleacetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Benzhydryl motifs in the 2-position of the thiazole was found to be most advantageous. The 4-thiazole position should either carry 3- or 4-fluorophenyl rings or a 4-pyridyl suitably substituted in the flanking 2-position. Several compounds with single digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained. The compound series display a good PK profile and selectivity over a large number of other targets.",
author = "Marie Grimstrup and {\O}ystein Rist and Jean-Marie Receveur and Frimurer, {Thomas M} and Trond Ulven and Mathiesen, {Jesper M} and Evi Kostenis and Thomas H{\"o}gberg",
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Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2. / Grimstrup, Marie; Rist, Øystein; Receveur, Jean-Marie; Frimurer, Thomas M; Ulven, Trond; Mathiesen, Jesper M; Kostenis, Evi; Högberg, Thomas.

I: Bioorganic & Medicinal Chemistry Letters, Bind 20, Nr. 3, 01.02.2010, s. 1181-5.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2

AU - Grimstrup, Marie

AU - Rist, Øystein

AU - Receveur, Jean-Marie

AU - Frimurer, Thomas M

AU - Ulven, Trond

AU - Mathiesen, Jesper M

AU - Kostenis, Evi

AU - Högberg, Thomas

N1 - Copyright (c) 2009 Elsevier Ltd. All rights reserved.

PY - 2010/2/1

Y1 - 2010/2/1

N2 - Structure-activity relationships have been established by exploring the eastern and western side of 5-thiazolyleacetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Benzhydryl motifs in the 2-position of the thiazole was found to be most advantageous. The 4-thiazole position should either carry 3- or 4-fluorophenyl rings or a 4-pyridyl suitably substituted in the flanking 2-position. Several compounds with single digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained. The compound series display a good PK profile and selectivity over a large number of other targets.

AB - Structure-activity relationships have been established by exploring the eastern and western side of 5-thiazolyleacetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Benzhydryl motifs in the 2-position of the thiazole was found to be most advantageous. The 4-thiazole position should either carry 3- or 4-fluorophenyl rings or a 4-pyridyl suitably substituted in the flanking 2-position. Several compounds with single digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained. The compound series display a good PK profile and selectivity over a large number of other targets.

U2 - 10.1016/j.bmcl.2009.12.015

DO - 10.1016/j.bmcl.2009.12.015

M3 - Journal article

C2 - 20022749

VL - 20

SP - 1181

EP - 1185

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 3

ER -