Polycyclic Sulfoximines as New Scaffolds for Drug Discovery.

The design and synthesis of three novel polycyclic scaffolds containing sulfoximines are presented in this work, which exemplify that sulfoximines represent a real opportunity for the discovery of new drug candidates. Additionally, the structures present at least two points of diversification and contain a high level of sp3-character, hence being very interesting 3D scaffolds. The compounds synthesized were added to the compound collection of the European Lead Factory.

Resolution of praziquantel.

BACKGROUND: Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extremely bitter taste of the pill. METHODOLOGY/PRINCIPAL FINDINGS: We have identified two resolution approaches toward the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine, which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself. CONCLUSIONS/SIGNIFICANCE: Both resolution procedures identified show promise for the large-scale, economically viable production of praziquantel as a single enantiomer for a low price. Additionally, they may be employed by laboratories for the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example, elucidation of the drug's mechanism of action.