Development of a novel conjugatable sunitinib analogue validated through in vitro and in vivo preclinical settings.

Sunitinib is an oral FDA/EMEA approved multi-targeted tyrosine kinase inhibitor. It possesses anti-angiogenic and antitumor activity against a variety of advanced solid tumors. However, its chemical core does not allow a potential linkage to tumor-homing elements that could eventually enhance its potency.

Menoctone Resistance in Malaria Parasites Is Conferred by M133I Mutations in Cytochrome That Are Transmissible through Mosquitoes.

Malaria-related mortality has slowly decreased over the past decade; however, eradication of malaria requires the development of new antimalarial chemotherapies that target liver stages of the parasite and combat the emergence of drug resistance. The diminishing arsenal of anti-liver-stage compounds sparked our interest in reviving the old and previously abandoned compound menoctone. In support of these studies, we developed a new convergent synthesis method that was facile, required fewer steps, produced better yields, and utilized less expensive reagents than the previously published method.

Novel synthesis of 3-substituted 2,3-dihydrobenzofurans via ortho-quinone methide intermediates generated in situ.

A new method is presented for the regioselective one-pot synthesis of 3-substituted 2,3-dihydrobenzofurans from 2-bromo-1-{2-[(triisopropylsilyl)oxy]phenyl}ethyl nitrate by fluoride-induced desilylation leading to o-quinone methide generation, Michael addition of different C, N, O, and S nucleophiles, and intramolecular 5-exo-tet elimination of a bromide anion. The method has potential synthetic applications in drug discovery.

Mild and rapid method for the generation of ortho-(naphtho)quinone methide intermediates.

A new mild method has been devised for generating o-(naphtho)quinone methides via fluoride-induced desilylation of silyl derivatives of o-hydroxybenzyl(or 1-naphthylmethyl) nitrate. The reactive o-(naphtho)quinone methide intermediates were trapped by C, O, N, and S nucleophiles and underwent "inverse electron-demand" hetero-Diels-Alder reaction with dienophiles to give stable adducts. The method has useful potential application in natural product synthesis and drug research.