A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound 32 bearing C-4′ 4-methoxyphenoxy and 4-(o-fluoropyridyl) carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3–42.7 nM), high intravenous AUC (64.9 μM· h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C= 32%, 20 mg/kg, ...
