Conformation-based restrictions and scaffold replacements in the design of hepatitis C virus polymerase inhibitors: discovery of deleobuvir (BI 207127)

…, J Rancourt, T Stammers, B Thavonekham…

Index: LaPlante, Steven R.; Boes, Michael; Brochu, Christian; Chabot, Catherine; Coulombe, Rene; Gillard, James R.; Jakalian, Araz; Poirier, Martin; Rancourt, Jean; Stammers, Timothy; Thavonekham, Bounkham; Beaulieu, Pierre L.; Kukolj, George; Tsantrizos, Youla S. Journal of Medicinal Chemistry, 2014 , vol. 57, # 5 p. 1845 - 1854

Full Text: HTML

Citation Number: 14

Abstract

Conformational restrictions of flexible torsion angles were used to guide the identification of new chemotypes of HCV NS5B inhibitors. Sites for rigidification were based on an acquired conformational understanding of compound binding requirements and the roles of substituents in the free and bound states. Chemical bioisosteres of amide bonds were explored to improve cell-based potency. Examples are shown, including the design ...

Related Articles:

Coupling reaction of alkenes with α-bromo carboxylic acid derivatives using nickel boride and borohydride exchange resin in methanol

[Joung, Meyoung Ju; Ahn, Jin Hee; Lee, Dong Won; Yoon, Nung Min Journal of Organic Chemistry, 1998 , vol. 63, # 8 p. 2755 - 2757]

Stereoselective synthesis of di-and trisubstituted alkenes via intermolecular addition of vinyl radicals to alkenes

[Miura, Katsukiyo; Itoh, Daisuke; Hondo, Takeshi; Hosomi, Akira Tetrahedron Letters, 1994 , vol. 35, # 51 p. 9605 - 9608]

Stereo-and regioselectivity of cyclization reactions in conformationally restricted epoxy ketones: evaluation of C-versus O-alkylation process

[Crotti, Paolo; Badalassi, Fabrizio; Di Bussolo, Valeria; Favero, Lucilla; Pineschi, Mauro Tetrahedron, 2001 , vol. 57, # 40 p. 8559 - 8572]

Stereo-and regioselectivity of cyclization reactions in conformationally restricted epoxy ketones: evaluation of C-versus O-alkylation process

[Crotti, Paolo; Badalassi, Fabrizio; Di Bussolo, Valeria; Favero, Lucilla; Pineschi, Mauro Tetrahedron, 2001 , vol. 57, # 40 p. 8559 - 8572]

Stereo-and regioselectivity of cyclization reactions in conformationally restricted epoxy ketones: evaluation of C-versus O-alkylation process

[Crotti, Paolo; Badalassi, Fabrizio; Di Bussolo, Valeria; Favero, Lucilla; Pineschi, Mauro Tetrahedron, 2001 , vol. 57, # 40 p. 8559 - 8572]

More Articles...