Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
Bioorg Med Chem Lett. 2009 Nov 15;19(22):6419-23. doi: 10.1016/j.bmcl.2009.09.052. Epub 2009 Sep 17.
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.
一系列苯乙酸衍生物被发现是 CRTH2 拮抗剂。对该系列化合物进行修饰，得到了 DP 拮抗剂。由于激活 CRTH2 和 DP 被认为在介导哮喘和其他免疫疾病的反应中起着关键作用，因此对该系列化合物进行了优化，以提高双重拮抗活性和改善药代动力学性质。这些努力导致选择 AMG 009 作为临床候选药物。
