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.

Formation of 4'-carboxyl acid metabolite of imrecoxib by rat liver microsomes.

Aim: Imrecoxib is a novel and moderately selective COX-2 inhibitor. The aim of the present in vitro investigation was to study the formation of the major metabolite 4'-carboxylic acid imrecoxib (M2) and identify the enzyme(s) involved in the reaction.

Methods: The formation of M2 was studied in rat liver cytosol in the absence or presence of liver microsome.