300832-84-2Relevant academic research and scientific papers
Sulfone-Mediated SNAr Reaction as a Powerful Tool for the Synthesis of 4-Quinolinyl Ethers and More-Application to the Synthesis of HCV NS3/4a Protease Inhibitor BI 201420
Patel, Nitinchandra D.,Wei, Xudong,Byrne, Denis,Narayanan, Bikshandarkoil A.,Pennino, Scott,Sarvestani, Max,Saha, Anjan,Haddad, Nizar,Kapadia, Suresh,Lorenz, Jon C.,Decroos, Philomen,Ye, Andrew,Lee, Heewon,Grinberg, Nelu,Hossain, Azad,Busacca, Carl A.,Yee, Nathan K.,Senanayake, Chris H.
, p. 8339 - 8351 (2020/07/16)
An efficient general methodology for the synthesis of 4-quinolinyl ethers is demonstrated via a highly reactive SNAr reaction of 4-quinolinyl sulfones with a range of structurally diversified 1°, 2°, and 3° alcohols with a wide substrate scope and high yields. By adapting this methodology, a convergent synthesis of a complex target of HCV NS3/4a protease inhibitor BI 201420 was accomplished.
A concise synthesis of the HCV protease inhibitor BILN 2061 and its P3 modified analogs
Liu, Dejun,Dong, Jingchao,Yin, Yunxing,Ma, Rujian,Shi, Yifeng,Wu, Hao,Chen, Shuhui,Li, Ge
, p. 1489 - 1502 (2011/11/01)
A concise synthesis of BILN 2061 was achieved through more efficient installation of P2 4-quinoline moiety via SN2 displacement of the β-OBs group located on the 4-hydroxyl proline intermediate, which was prepared from 4-α-hydroxyl proline analog via Mitsunobu reaction with inversion of stereochemistry. In addition, a short and practical synthesis for P3 unit is also described herein. Final assembly of four fragments for BILN 2061 was achieved with an overall yield of 58% in 4 steps from P1 to 15a. Furthermore several analogs of BILN 2061 (WX-1-WX-5) containing modifications on P3 unit were synthesized successfully using the same synthetic route as described for the parent inhibitor BILN 2061. Copyright
Efficient large-scale synthesis of BILN 2061, a potent HCV protease inhibitor, by a convergent approach based on ring-closing metathesis
Yee, Nathan K.,Farina, Vittorio,Houpis, Ioannis N.,Haddad, Nizar,Frutos, Rogelio P.,Gallou, Fabrice,Wang, Xiao-Jun,Wei, Xudong,Simpson, Robert D.,Feng, Xuwu,Fuchs, Victor,Xu, Yibo,Tan, Jonathan,Zhang, Li,Xu, Jinghua,Smith-Keenan, Lana L.,Vitous, Jana,Ridges, Michael D.,Spinelli, Earl M.,Johnson, Michael,Donsbach, Kai,Nicola, Thomas,Brenner, Michael,Winter, Eric,Kreye, Paul,Samstag, Wendelin
, p. 7133 - 7145 (2007/10/03)
A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metath
Structure-Activity Study on a Novel Series of Macrocyclic Inhibitors of the Hepatitis C Virus NS3 Protease Leading to the Discovery of BILN 2061
Llinàs-Brunet, Montse,Bailey, Murray D.,Bolger, Gordon,Brochu, Christian,Faucher, Anne-Marie,Ferland, Jean Marie,Garneau, Michel,Ghiro, Elise,Gorys, Vida,Grand-Ma?tre, Chantal,Halmos, Ted,Lapeyre-Paquette, Nicole,Liard, Francine,Poirier, Martin,Rhéaume, Manon,Tsantrizos, Youla S.,Lamarre, Daniel
, p. 1605 - 1608 (2007/10/03)
From the discovery of competitive hexapeptide inhibitors, potent and selective HCV NS3 protease macrocyclic inhibitors have been identified. Structure-activity relationship studies were performed focusing on optimizing the N-terminal carbamate and the aromatic substituent on the (4R) -hydroxyproline moiety. Inhibitors meeting the potency criteria in the cell-based assay and with improved oral bioavailability in rats were identified. BILN 2061 was selected as the best compound, the first NS3 protease inhibitor reported with antiviral activity in man.
Synthesis of BILN 2061, an HCV NS3 protease inhibitor with proven antiviral effect in humans
Faucher, Anne-Marie,Bailey, Murray D.,Beaulieu, Pierre L.,Brochu, Christian,Duceppe, Jean-Simon,Ferland, Jean-Marie,Ghiro, Elise,Gorys, Vida,Halmos, Ted,Kawai, Stephen H.,Poirier, Martin,Simoneau, Bruno,Tsantrizos, Youla S.,Llinas-Brunet, Montse
, p. 2901 - 2904 (2007/10/03)
(Equation Presented) The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigra
