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 for this work

15 Citations (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.

Original language	English
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	5
Pages (from-to)	1638-1641
Number of pages	4
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2010.01.092
Publication status	Published - 1 Mar 2010

Keywords

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

Access to Document

10.1016/j.bmcl.2010.01.092

Cite this

@article{d65d68c119014f36a6af77fb10ffefa5,

title = "Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists",

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",

year = "2010",

month = mar,

day = "1",

doi = "10.1016/j.bmcl.2010.01.092",

language = "English",

volume = "20",

pages = "1638--1641",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Pergamon Press",

number = "5",

}

TY - JOUR

T1 - Exploration of SAR features by modifications of thiazoleacetic acids as CRTH2 antagonists

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

PY - 2010/3/1

Y1 - 2010/3/1

N2 - 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.

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

UR - http://www.scopus.com/inward/record.url?scp=76649106066&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2010.01.092

DO - 10.1016/j.bmcl.2010.01.092

M3 - Journal article

C2 - 20137942

AN - SCOPUS:76649106066

SN - 0960-894X

VL - 20

SP - 1638

EP - 1641

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 5

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this