Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo.

The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties.

Asymmetry by electrophilic rearrangement of symmetric 2-pyridone photodimers.

[reaction: see text] Halogenation of achiral trans-2-pyridone photodimers results in 1,3-migration of an amide nitrogen and formation of a chiral structure with six stereogenic centers and well-differentiated functionality. The reactivity of this product toward nucleophiles, including the allylic halide, is dominated by participation by the amide nitrogen.

Substituted indanylacetic acids as PPAR-alpha-gamma activators.

A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes.

Substituted aminobenzimidazole pyrimidines as cyclin-dependent kinase inhibitors.

A series of aminobenzimidazole-substituted pyrimidines were synthesized and evaluated for biochemical activity against CDK1. A high-speed parallel synthesis approach enabled the identification of a potent lead series having improved potency in the CDK1 assay (IC(50)<10nM). Cell cycle analysis showed that the compounds induced a G2/M block.