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Novel selective orally active CRTH2 antagonists for allergic inflammation developed from in silico derived hits

Ulven, Trond; Receveur, Jean-Marie; Grimstrup, Marie; Rist, Oystein; Frimurer, Thomas M; Gerlach, Lars-Ole; Mathiesen, Jesper Mosolff; Kostenis, Evi; Uller, Lena LU and Hogberg, Thomas (2006) In Journal of Medicinal Chemistry 49(23). p.6638-6641
Abstract
Hits from an in silico derived focused library for CRTH2 were transformed into highly selective antagonists with favorable ADME properties. Oral administration of 4-bromo-2-(1-phenyl-1H-pyrazole-4-carbonyl)phenoxyacetic acid (19) inhibited peribronchial eosinophilia and mucus cell hyperplasia in a mouse model of allergic asthma, supporting the therapeutic potential of this novel compound class. In addition, this selective pharmacological tool compound provides further evidence for CRTH2 as a relevant therapeutic target for treatment of Th2- and eosinophil-related inflammation.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
49
issue
23
pages
6638 - 6641
publisher
The American Chemical Society
external identifiers
  • WOS:000241894000003
  • Scopus:33750978443
ISSN
1520-4804
DOI
10.1021/jm060657g
language
English
LU publication?
yes
id
7f634cad-043f-472f-8bc3-359da9a08b4a (old id 1298261)
date added to LUP
2009-07-13 08:53:30
date last changed
2016-11-16 10:23:21
@misc{7f634cad-043f-472f-8bc3-359da9a08b4a,
  abstract     = {Hits from an in silico derived focused library for CRTH2 were transformed into highly selective antagonists with favorable ADME properties. Oral administration of 4-bromo-2-(1-phenyl-1H-pyrazole-4-carbonyl)phenoxyacetic acid (19) inhibited peribronchial eosinophilia and mucus cell hyperplasia in a mouse model of allergic asthma, supporting the therapeutic potential of this novel compound class. In addition, this selective pharmacological tool compound provides further evidence for CRTH2 as a relevant therapeutic target for treatment of Th2- and eosinophil-related inflammation.},
  author       = {Ulven, Trond and Receveur, Jean-Marie and Grimstrup, Marie and Rist, Oystein and Frimurer, Thomas M and Gerlach, Lars-Ole and Mathiesen, Jesper Mosolff and Kostenis, Evi and Uller, Lena and Hogberg, Thomas},
  issn         = {1520-4804},
  language     = {eng},
  number       = {23},
  pages        = {6638--6641},
  publisher    = {ARRAY(0xa9d3f90)},
  series       = {Journal of Medicinal Chemistry},
  title        = {Novel selective orally active CRTH2 antagonists for allergic inflammation developed from in silico derived hits},
  url          = {http://dx.doi.org/10.1021/jm060657g},
  volume       = {49},
  year         = {2006},
}