Al-Awar Rima S, Ray James E, Schultz Richard M, Andis Sherri L, Kennedy Joseph H, Moore Richard E, Liang Jian, Golakoti Trimurtulu, Subbaraju Gottumukkala V, Corbett Thomas H
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
J Med Chem. 2003 Jul 3;46(14):2985-3007. doi: 10.1021/jm0203884.
Cryptophycin 52 is a synthetic derivative of Cryptophycin 1, a potent antimicrotubule agent isolated from cyanobacteria. In an effort to increase the potency and water solubility of the molecule, a structure-activity relationship study (SAR) was initiated around the phenyl ring of fragment A. These Cryptophycin 52 analogues were accessed using a Wittig olefination reaction between various triphenylphosphonium salts and a key intermediate aldehyde prepared from Cryptophycin 53. Substitution on the phenyl ring of fragment A was well tolerated, and several of these analogues were equally or more potent than Cryptophycin 52 when evaluated in vitro in the CCRF-CEM leukemia cell line and in vivo against a murine pancreatic adenocarcinoma.
隐藻素52是隐藻素1的合成衍生物，隐藻素1是一种从蓝细菌中分离出的强效抗微管剂。为了提高该分子的效力和水溶性，围绕片段A的苯环开展了构效关系研究（SAR）。这些隐藻素52类似物是通过各种三苯基鏻盐与由隐藻素53制备的关键中间体醛之间的维蒂希烯烃化反应得到的。片段A苯环上的取代具有良好的耐受性，在CCRF-CEM白血病细胞系中进行体外评估以及在体内对抗小鼠胰腺腺癌时，其中几种类似物的效力与隐藻素52相当或更强。
