Design, Synthesis and Discovery of 1-(2-(6-Chloro-3-methylsulfonyl)-naphthyl)-1H pyrazole-5-carboxylamides as Highly Potent Factor Xa Inhibitors
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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
27
References
2
Citations
NaN
KQI