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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

14 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	20
Udgave nummer	3
Sider (fra-til)	1181-1185
Antal sider	5
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2009.12.015
Status	Udgivet - 1 feb. 2010

Bibliografisk note

Adgang til dokumentet

10.1016/j.bmcl.2009.12.015

Citationsformater

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. 1181-1185.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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

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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.

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