Kiang Y-H, Nagapudi Karthik, Wu Tian, Peterson Matthew L, Jona Janan, Staples Richard J, Stephens Peter W
Process Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California, 91320.
Process Development, Amgen Inc., Cambridge, Massachusetts, 02142.
J Pharm Sci. 2015 Jul;104(7):2161-8. doi: 10.1002/jps.24457. Epub 2015 Apr 24.
Investigation of an additional resonance peak in the (19) F solid-state nuclear magnetic resonance (NMR) spectrum of AMG 853, a dual antagonist of DP and CRTH2 previously in clinical development for asthma, has led to the identification of two conformational isomers coexisting in the crystal lattice in a continuous composition range between 89.7%:10.3% and 96.5%:3.5%. These two isomers differ in the chloro-flurorophenyl moiety orientation-the aromatic ring is flipped by 180° in these two isomers. The level of the minor isomer is directly measured through integration of the two peaks in the (19) F solid-state NMR spectrum. The values obtained from the NMR data are in excellent agreement with the degree of disorder of the fluorine atom in the crystal structure, refined using both single-crystal and high-resolution powder X-ray diffraction data.
对AMG 853（一种DP和CRTH2的双重拮抗剂，此前处于哮喘临床开发阶段）的¹⁹F固态核磁共振（NMR）谱中一个额外共振峰的研究，已导致鉴定出两种构象异构体，它们在晶格中共存，其连续组成范围在89.7%:10.3%至96.5%:3.5%之间。这两种异构体在氯氟苯基部分的取向上有所不同——在这两种异构体中芳环翻转了180°。通过对¹⁹F固态NMR谱中的两个峰进行积分，直接测量了次要异构体的含量。从NMR数据获得的值与使用单晶和高分辨率粉末X射线衍射数据精修得到的晶体结构中氟原子的无序程度非常吻合。
