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

Research output: Contribution to journalJournal articleResearchpeer-review

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 languageEnglish
JournalBioorganic & Medicinal Chemistry Letters
Volume20
Issue number3
Pages (from-to)1181-5
Number of pages4
ISSN0960-894X
DOIs
Publication statusPublished - 1. Feb 2010

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