Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Eur J Med Chem. 2011 Oct;46(10):5108-19. doi: 10.1016/j.ejmech.2011.08.025. Epub 2011 Aug 23.
The in vitro cytotoxicity assays of several enantiopure (3S,4S)- and (3R,4R)-1,3,4,4-tetrasubstituted β-lactams derived from amino acids have shown that the (3S,4S)-4-benzyl-1-p-methoxybenzyl-3-methyl-4-methoxycarbonyl derivative 2a, obtained from Phe, displays significant activity, which is comparable to that of the anticancer drug Doxorubicin against HT29 cell lines. Modifications at positions 1 and 4 of the β-lactam ring led to identify the Tyr(2,6-ClBz) analogu 26d with similar activity data to those of 2a. The synthesis and SAR of all these tetrasubstituted β-lactams are reported here.
几种手性纯（3S,4S）-和（3R,4R）-衍生自氨基酸的 1,3,4,4-四取代β-内酰胺的体外细胞毒性测定表明，从苯丙氨酸获得的（3S,4S）-4-苄基-1-对甲氧苄基-3-甲基-4-甲氧羰基衍生物 2a 显示出显著的活性，与抗癌药物阿霉素对 HT29 细胞系的活性相当。β-内酰胺环 1 位和 4 位的修饰导致确定了 Tyr(2,6-ClBz)类似物 26d，其活性数据与 2a 相似。本文报道了所有这些四取代β-内酰胺的合成和 SAR。
