173416-63-2

Upstream product

• 173416-61-0 (R)-(+)-3,4-dihydro-6-<2-hydroxy-3-(1-o-tolyl-2-imidazolyl)thiopropoxy>-2(1H)-quinolinone 
• 512790-83-9 (R)-6-(oxiran-2-ylmethoxy)-3,4-dihydroquinolin-2(1H)-one 
• 54197-66-9 3,4-dihydro-6-hydroxy-2(1H)-quinolinone 
• 124-63-0 methanesulfonyl chloride 
• 173416-62-1 3,4-dihydro-6-<2(R)-hydroxy-3-<1-(2-methylphenyl)-2-imidazolyl>-(S)-sulfinylpropoxy>-2(1H)-quinolinone 

Downstream Products

• 161190-38-1 (S)-(+)-3,4-dihydro-6-<3-(1-o-tolyl-2-imidazolyl)sulfinylpropoxy>-2(1H)-quinolinone 

Relevant academic research and scientific papers

The improved synthesis of OPC-29030, a platelet adhesion inhibitor via diastereoselective oxidation of chiral non-racemic sulfide

An improved synthetic route of OPC-29030, the platelet adhesion inhibitor, was established via the diastereoselective oxidation of a chiral non-racemic sulfide (R)-5 to (SS)-6 by the catalytic oxidation using VO(acac)2 and cumene hydroperoxide (CHP) in the presence of MS4A. Under the current condition, the diastereoselectivity was not influenced by the presence of moisture, and moderate to high selectivity (72% de) was obtained at -30°C. The obtained sulfoxide, which diastereomeric excess was easily raised by the recrystallization, could successfully lead to OPC-29030.

Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets

A search for potent inhibitors of release of 12(S)- hydroxyeicosatetraenoic acid (12-HETE), which plays an important role in the pathogenesis of various circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5-tetrazolyl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)-quinolinone derivatives having an azole group in the side chain. Many 2(1H)-quinolinone derivatives were synthesized and tested in vitro for the inhibitory activity in human platelets. 3,4-Dihydro-6-[3-(1-o- tolylimidazol-2-yl)sulfinylpropoxy]-2(1H)-quinolinone (5k) was found to be one of the most potent inhibitors of 12-HETE release, being more potent than esculetin. In addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet adhesion in rats. Since 5k is racemic, the enantiomers were prepared and their potencies were compared in vitro and in vivo. (S)-(+)-5k had the best pharmacological profile and was selected as a candidate drug for further development. The structure-activity relationships are discussed.