Discovery of AMG 853, a CRTH2 and DP dual antagonist
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 rece
Liu, Jiwen,Li, An-Rong,Wang, Yingcai,Johnson, Mike G.,Su, Yongli,Shen, Wang,Wang, Xuemei,Lively, Sarah,Brown, Matthew,Lai, Sujen,Gonzalez Lopez De Turiso, Felix,Xu, Qingge,Van Lengerich, Bettina,Schmitt, Mike,Fu, Zice,Sun, Ying,Lawlis, Shanna,Seitz, Lisa,Danao, Jay,Wait, Jill,Ye, Qiuping,Tang, Hua Lucy,Grillo, Mark,Collins, Tassie L.,Sullivan, Timothy J.,Medina, Julio C.
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(2011/07/09)
Discovery and optimization of CRTH2 and DP dual antagonists
A series of phenylacetic acid derivatives was discovered as CRTH2 antagonists. Modification of the series led to compounds that are also antagonists of DP. Since activation of CRTH2 and DP are believed to play key roles in mediating responses of asthma and other immune diseases, this series was optimized to increase the dual antagonistic activities and improve pharmacokinetic properties. These efforts led to selection of AMG 009 as a clinical candidate.