CX-516

A phosphine-free, efficient protocol for aminocarbonylation and carbonylative Suzuki-Miyaura coupling has been developed using a novel palladium complex, [Pd^II(DMAP)₂(OAc)₂]. The complex was successfully synthesized using a stoichiometric reaction between Pd^II(OAc)₂ and DMAP in acetone at room temperature and characterized using single-crystal X-ray analysis. Only 5 mol % catalyst loading was sufficient for effective carbonylative transformations. "Chloroform-COware" chemistry was utilized for safe and facile insertion of the carbonyl unit using chloroform as an inexpensive CO source in a two-chamber setup. Various value-added pharmaceutically relevant compounds such as CX-516, CX-546, and farampator were synthesized using the technique. Furthermore, the commercially designed COware was engineered to COware-RB setup for sequential one-pot synthesis of indenoisoquinolines (topoisomerase I inhibitors).

Most patients with plaque psoriasis exhibit mild-to-moderate disease and topical therapies remain the mainstay treatment option for these patients. The use of topical steroids in combination with vitamin D analogs can produce synergistic effects and minimize adverse effects. However, due to the incompatible pH ranges of topical steroids and vitamin D analogs, combination formulations can be difficult to manufacture. Until recently, only anhydrous formulations of these 2 agents were developed as foam, gel/suspension, and ointment. However, anhydrous vehicles can often result in greasy or oily skin, thus limiting treatment adherence. Recently, Polyaphron Dispersion (PAD) technology presents a new, more cosmetically appealing vehicle that allows for both topical steroids and vitamin D analogs to coexist in an aqueous environment, such as a cream formulation. The calcipotriene/betamethasone dipropionate (CAL/BDP) cream enhances drug delivery by reducing the greasy and oily side effects of anhydrous formulations. Phase 3 clinical trials have demonstrated CAL/BDP cream’s superior efficacy in treating psoriasis over gel/suspension, and the clinical trials have also shown significantly improved patient satisfaction with the cream formulation.   .