Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
Bioorg Med Chem Lett. 2012 Jan 1;22(1):367-70. doi: 10.1016/j.bmcl.2011.10.123. Epub 2011 Nov 9.
We have previously reported that optimization of a series of phenylacetic acid derivatives led to the discovery of CRTH2 and DP dual antagonists, such as AMG 009 and AMG 853. During the optimization process, we discovered that minor structural modifications also afforded potent and selective CRTH2 or DP antagonists. Here we report the structure-activity relationship that led to the discovery of selective CRTH2 antagonists such as 2 and 17, and selective DP antagonists, such as 4 and 5.
我们之前曾报道过，对一系列苯乙酸衍生物进行优化，发现了 CRTH2 和 DP 双重拮抗剂，如 AMG 009 和 AMG 853。在优化过程中，我们发现微小的结构修饰也能得到有效的、选择性的 CRTH2 或 DP 拮抗剂。在此，我们报告了导致发现选择性 CRTH2 拮抗剂，如 2 和 17，以及选择性 DP 拮抗剂，如 4 和 5 的构效关系。
