1202165-79-4Relevant academic research and scientific papers
Design, synthesis and discovery of 1-(2-(6-chloro-3-methylsulfonyl)- naphthyl)-1H-pyrazole-5-carboxylamides as highly potent factor Xa inhibitors
Jia, Zhaozhong Jon,Scarborough, Robert Murry,Zhang, Penglie,Halfon, Sherin,Arfsten, Ann Elizabeth,Sinha, Uma,Zhu, Bing-Yan
, p. 1004 - 1007 (2009)
Based upon the biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides reported in our previous communications, we designed and discovered 2-(6-chloro-3-methylsulfonyl)-naphthyl as an optimal factor Xa S1 binding element. Employing a key Diels-Alder reaction of 1,4-dihydro-2,3-benzoxathiin-3- oxide with maleic anhydride and a key Cu(I)-mediated methylsulfonylation, we prepared two biphenyl 1-(2-(6-chloro-3-methylsulfonyl)-naphthyl)-1H-pyrazole-5- carboxylamides as highly potent factor Xa inhibitors with Ki values of 0.065 nM and 0.045 nM respectively, and demonstrated the synergistically enhanced binding interaction in the factor Xa S1 site.
