| Literature DB >> 24900313 |
Jiwen Liu1, An-Rong Li1, Yingcai Wang1, Mike G Johnson1, Yongli Su1, Wang Shen1, Xuemei Wang1, Sarah Lively1, Matthew Brown1, SuJen Lai1, Felix Gonzalez Lopez De Turiso1, Qingge Xu1, Bettina Van Lengerich1, Mike Schmitt1, Zice Fu1, Ying Sun1, Shanna Lawlis1, Lisa Seitz1, Jay Danao1, Jill Wait1, Qiuping Ye1, Hua Lucy Tang1, Mark Grillo1, Tassie L Collins1, Timothy J Sullivan1, Julio C Medina1.
Abstract
Prostaglandin D2 (PGD2) plays a key role in mediating allergic reactions seen in asthma, allergic rhinitis, and atopic dermatitis. PGD2 exerts its activity through two G protein-coupled receptors (GPCRs), prostanoid D receptor (DP or DP1), and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 or DP2). We report the optimization of a series of phenylacetic acid derivatives in an effort to improve the dual activity of AMG 009 against DP and CRTH2. These efforts led to the discovery of AMG 853 (2-(4-(4-(tert-butylcarbamoyl)-2-(2-chloro-4-cyclopropylphenyl sulfonamido)phenoxy)-5-chloro-2-fluorophenyl)acetic acid), which is being evaluated in human clinical trials for asthma.Entities:
Keywords: AMG 853; CRTH2 receptor; DP receptor; antagonist; asthma; prostaglandin D2
Year: 2011 PMID： 24900313 PMCID： PMC4018074 DOI： 10.1021/ml1002234
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345