Robert W. Mcnutt

The discovery of potent cRaf1 kinase inhibitors.

A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compounds with low nanomolar kinase enzyme inhibition and inhibited the intracellular MAPK pathway.

AN EFFICIENT SYNTHESIS OF THE BENZHYDRYLPIPERAZINE DELTA OPIOID AGONIST (+)-BW373U86

A diastereoselective version of Katritzkys method for tertiary amine formation provides an efficient route to the highly selective, non-peptidal, delta opioid agonist (+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl]-N,N-diethylbenzamide [(+)-BW373U86], 1.