Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists

Marie Grimstrup; Jean Marie Receveur; Øystein Rist; Thomas M. Frimurer; Peter Aadal Nielsen; Jesper M. Mathiesen; Thomas Högberg

doi:10.1016/j.bmcl.2010.01.092

Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists

Marie Grimstrup, Jean Marie Receveur, Øystein Rist, Thomas M. Frimurer, Peter Aadal Nielsen, Jesper M. Mathiesen, Thomas Högberg^*

^*Corresponding author af dette arbejde

15 Citationer (Scopus)

Abstract

The SAR features have been further explored for (2-benzhydryl-4-phenyl-thiazol-5-yl)acetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. The introduction of a nitrogen or a methyl substituent in the benzhydrylic position offer two alternative drugable scaffolds attractive for unsymmetrically substituted derivatives. An imidazole analogue lacks activity due to formation of a favored coplanar intramolecular hydrogen bond. The pyrimidine derivative 18 represents a potent and selective compound that will be subject to continued investigations.

Originalsprog	Engelsk
Tidsskrift	Bioorganic and Medicinal Chemistry Letters
Vol/bind	20
Udgave nummer	5
Sider (fra-til)	1638-1641
Antal sider	4
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2010.01.092
Status	Udgivet - 1 mar. 2010

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10.1016/j.bmcl.2010.01.092

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abstract = "The SAR features have been further explored for (2-benzhydryl-4-phenyl-thiazol-5-yl)acetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. The introduction of a nitrogen or a methyl substituent in the benzhydrylic position offer two alternative drugable scaffolds attractive for unsymmetrically substituted derivatives. An imidazole analogue lacks activity due to formation of a favored coplanar intramolecular hydrogen bond. The pyrimidine derivative 18 represents a potent and selective compound that will be subject to continued investigations.",

keywords = "Chemoattractant receptor-homologous molecule expressed on Th2 cells, CRTH2 antagonists, Molecular modelling, PGD2, Scaffold hopping, Structure-activity relationships",

author = "Marie Grimstrup and Receveur, {Jean Marie} and {\O}ystein Rist and Frimurer, {Thomas M.} and Nielsen, {Peter Aadal} and Mathiesen, {Jesper M.} and Thomas H{\"o}gberg",

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AU - Grimstrup, Marie

AU - Receveur, Jean Marie

AU - Rist, Øystein

AU - Frimurer, Thomas M.

AU - Nielsen, Peter Aadal

AU - Mathiesen, Jesper M.

AU - Högberg, Thomas

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AB - The SAR features have been further explored for (2-benzhydryl-4-phenyl-thiazol-5-yl)acetic acids as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. The introduction of a nitrogen or a methyl substituent in the benzhydrylic position offer two alternative drugable scaffolds attractive for unsymmetrically substituted derivatives. An imidazole analogue lacks activity due to formation of a favored coplanar intramolecular hydrogen bond. The pyrimidine derivative 18 represents a potent and selective compound that will be subject to continued investigations.

KW - Chemoattractant receptor-homologous molecule expressed on Th2 cells

KW - CRTH2 antagonists

KW - Molecular modelling

KW - PGD2

KW - Scaffold hopping

KW - Structure-activity relationships

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U2 - 10.1016/j.bmcl.2010.01.092

DO - 10.1016/j.bmcl.2010.01.092

M3 - Journal article

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SN - 0960-894X

VL - 20

SP - 1638

EP - 1641

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

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Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists

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