Novel indoline-1- or 3,4-dihydroquinoline-1(2H)-substituted carbothiohydrazides as TPO receptor agonists.

Synthesis and evaluation of novel series of indoline-1- or 3,4-dihydroquinoline-1(2H)-substituted carbothiohydrazide or carbohydrazide based small molecule compounds as thrombopoietin (TPO) receptor agonists are reported. Members of these compounds have been identified as full agonists of human c-mpl in BaF3/TPOR cell line. Indoline-1-carbohydrazide 9b exhibited reasonable pharmacokinetic profile.

Synthesis and biological evaluation of oxoindolin-3-ylidene ethyl benzothiohydrazides as non-peptide TPO mimics.

A novel series of oxoindolin-3-ylidene ethyl benzohydrazides were designed, synthesized, and identified as small molecule agonists of thrombopoietin (TPO) receptor c-mpl. Sulfur-oxygen exchange in oxoindolin-3-ylidene ethyl benzohydrazides was found to improve their agonistic activities. Several oxoindolin-3-ylidene ethyl benzothiohydrazides have been identified as full agonists of c-mpl.

Synthesis and biological evaluation of pyrrolopyridazine derivatives as novel HER-2 tyrosine kinase inhibitors.

A series of novel pyrrolopyridazine derivatives have been discovered to be HER-2 inhibitors. These compounds selectively inhibited HER-2 kinase activity at low nanomolar concentrations. Compound 7d was identified as a potent HER-2 inhibitor with an IC(50) of 4 nM.

Synthesis and biological evaluation of C-12' substituted vinflunine derivatives.

A series of novel C-12' substituted vinflunine derivatives have been synthesized. Several compounds in this series possess comparable in vitro cytotoxic potency against A549 cell lines.

Regiospecific and stereoselective syntheses of (+/-)-reserpine and (-)-reserpine.

Full details of three approaches to an entirely regio- and stereoselective synthesis of the well-known target reserpine are described, culminating in a total synthesis which efficiently meets these requirements.