Rational Design and Synthesis of Highly Potent Pharmacological Chaperones for Treatment of N370S Mutant Gaucher Disease

Abstract

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).