首个C2-C3/C2'-C3'-内型不饱和吡咯并[2,1-c][1,4]苯并二氮杂卓二聚体的合成。
Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer.
作者信息
Gregson S J, Howard P W, Corcoran K E, Jenkins T C, Kelland L R, Thurston D E
机构信息
CRC Gene Targeted Drug Design Research Group, Cancer Research Laboratories, School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
出版信息
Bioorg Med Chem Lett. 2001 Nov 5;11(21):2859-62. doi: 10.1016/s0960-894x(01)00560-1.
We report the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer 16 synthesised through a new and efficient route, thus establishing that C2-C3-endo unsaturation enhances both cytotoxicity and DNA-binding affinity in A-Ring-linked PBD dimers but to a lesser extent than C2/C2'-exo-unsaturation. This new route has allowed the preparation of multi-gram quantities of the related clinical candidate 1 and should lead to more structurally diverse PBD dimer analogues.
我们报道了通过一条新的高效路线合成的C2-C3/C2'-C3'-内型不饱和吡咯并[2,1-c][1,4]苯并二氮杂卓（PBD）二聚体16的首个实例，从而证实C2-C3-内型不饱和增强了A环连接的PBD二聚体的细胞毒性和DNA结合亲和力，但程度小于C2/C2'-外型不饱和。这条新路线使得能够制备数克量的相关临床候选药物1，并有望产生更多结构多样的PBD二聚体类似物。
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