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

Authors :: Marie Grimstrup
Jesper Mosolff Mathiesen
Trond Ulven
Thomas Högberg
Jean-Marie Receveur
Evi Kostenis
Thomas M. Frimurer
Øystein Rist
Source :: Grimstrup, M, Rist, Ø, Receveur, J-M, Frimurer, T M, Ulven, T, Mathiesen, J M, Kostenis, E & Högberg, T 2010, ' Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2 ', Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 3, pp. 1181-5 . https://doi.org/10.1016/j.bmcl.2009.12.015
Publication Year :: 2010
Abstract: Udgivelsesdato: 2010-Feb-1 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.

Language :: English
Database :: OpenAIRE
Journal :: Grimstrup, M, Rist, Ø, Receveur, J-M, Frimurer, T M, Ulven, T, Mathiesen, J M, Kostenis, E & Högberg, T 2010, ' Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2 ', Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 3, pp. 1181-5 . https://doi.org/10.1016/j.bmcl.2009.12.015
Accession number :: edsair.doi.dedup.....1ec36c8fce512bae3aabc5d2f9e81f16
Full Text :: https://doi.org/10.1016/j.bmcl.2009.12.015

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