Rational design and synthesis of highly potent pharmacological chaperones for treatment of N370S mutant Gaucher disease.

Research paper by Guan-Nan GN Wang, Gabriele G Reinkensmeier, Si-Wei SW Zhang, Jian J Zhou, Liang-Ren LR Zhang, Li-He LH Zhang, Terry D TD Butters, Xin-Shan XS Ye

Indexed on: 29 Apr '09Published on: 29 Apr '09Published in: Journal of Medicinal Chemistry


Highly potent N-substituted delta-lactams have been rationally designed and synthesized by a concise route with a one-pot tandem reaction as key step. These iminosugars show weak inhibition of wild-type beta-glucocerebrosidase but 3- to 6-fold increases in mutant enzyme activity (N370S).