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

doi:10.1016/j.bmcl.2009.12.015

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

14 Citations (Scopus)

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.

Original language	English
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	20
Issue number	3
Pages (from-to)	1181-1185
Number of pages	5
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2009.12.015
Publication status	Published - 1 Feb 2010

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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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language = "English",

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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

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

SN - 0960-894X

VL - 20

SP - 1181

EP - 1185

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 3

ER -

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

Abstract

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