Selective mono-de-O-acetylation of the per-O-acetylated brasilicardin carbohydrate side chain.

Methanol dried over powdered 4 Å molecular sieves can be used for a selective mono-de-O-acetylation of the phenolic acetyl group of the per-O-acetyl protected brasilicardin A carbohydrate side chain. This reaction opens a practical procedure for a synthetic access to derivates of the immunosuppressive and cytotoxic natural product brasilicardin A.

Recent progress in chemical approaches for the development of novel neuraminidase inhibitors.

Influenza virus is the main cause of an infectious disease called influenza affecting the respiratory system including the throat, nose and lungs. Neuraminidase inhibitors are reagents used to block the enzyme called neuraminidase to prevent the influenza infection from spreading. Neuraminidase inhibitors are widely used in the treatment of influenza infection, but still there is a need to develop more potent agents for the more effective treatment of influenza. Complications of the influenza disease lead to death, and one of these complications is drug resistance; hence, there is an urgent need to develop more effective agents. This review focuses on the recent advances in chemical synthesis pathways used for the development of new neuraminidase agents along with the medicinal aspects of chemically modified molecules, including the structure-activity relationship, which provides further rational designs of more active small molecules.

Medicinal chemistry of oxazines as promising agents in drug discovery.

Oxazines have brought much synthetic interest due to their extensive biological activities. These are the important category of heterocycles, which may be formally derived from benzene and its reduction products by convenient substitution of carbon (and hydrogen) atoms by nitrogen and oxygen. In the last few decades, oxazine derivatives have documented as worthy synthetic intermediates and also blessed with notable sedative, analgesic, anticonvulsant, antipyretic, antimicrobial, antitubercular, antimalarial, antioxidant, and anticancer activities. Nowadays, it is important to develop new classes of compounds with more effective mechanisms due to drug resistance activity in which the ability of drug to effectively treat disease can be reduced. The aim of the article is to collect and make a more generalized review on the synthesis of oxazine derivatives and their pharmaceutical and biological activities. We hope this review will provide ample references for the researchers concerned with azines in generally and oxazines in particular.

Structural Optimization of a Pyridinylimidazole Scaffold: Shifting the Selectivity from p38α Mitogen-Activated Protein Kinase to c-Jun N-Terminal Kinase 3.

Starting from known p38α mitogen-activated protein kinase (MAPK) inhibitors, a series of inhibitors of the c-Jun N-terminal kinase (JNK) 3 was obtained. Altering the substitution pattern of the pyridinylimidazole scaffold proved to be effective in shifting the inhibitory activity from the original target p38α MAPK to the closely related JNK3. In particular, a significant improvement for JNK3 selectivity could be achieved by addressing the hydrophobic region I with a small methyl group. Furthermore, additional structural modifications permitted to explore structure-activity relationships. The most potent inhibitor 4-(4-methyl-2-(methylthio)-1H-imidazol-5-yl)-N-(4-morpholinophenyl)pyridin-2-amine showed an IC50 value for the JNK3 in the low triple digit nanomolar range and its binding mode was confirmed by X-ray crystallography.