630421-42-0Relevant articles and documents
P2-quinazolinones and bis-macrocycles as new templates for next-generation hepatitis C virus NS3/4a protease inhibitors: Discovery of MK-2748 and MK-6325
Rudd, Michael T.,Butcher, John W.,Nguyen, Kevin T.,McIntyre, Charles J.,Romano, Joseph J.,Gilbert, Kevin F.,Bush, Kimberly J.,Liverton, Nigel J.,Holloway, M. Katharine,Harper, Steven,Ferrara, Marco,Difilippo, Marcello,Summa, Vincenzo,Swestock, John,Fritzen, Jeff,Carroll, Steven S.,Burlein, Christine,Dimuzio, Jillian M.,Gates, Adam,Graham, Donald J.,Huang, Qian,McClain, Stephanie,McHale, Carolyn,Stahlhut, Mark W.,Black, Stuart,Chase, Robert,Soriano, Aileen,Fandozzi, Christine M.,Taylor, Anne,Trainor, Nicole,Olsen, David B.,Coleman, Paul J.,Ludmerer, Steven W.,McCauley, John A.
, p. 727 - 735 (2015)
With the goal of identifying inhibitors of hepatitis C virus (HCV) NS3/4a protease that are potent against a wide range of genotypes and clinically relevant mutant viruses, several subseries of macrocycles were investigated based on observations made during the discovery of MK-5172. Quinazolinone-containing macrocycles were identified as promising leads, and optimization for superior cross-genotype and mutant enzyme potency as well as rat liver and plasma concentrations following oral dosing, led to the development of MK-2748. Additional investigation of a series of bis-macrocycles containing a fused 18- and 15-membered ring system were also optimized for the same properties, leading to the discovery of MK-6325. Both compounds display the broad genotype and mutant potency necessary for clinical development as next-generation HCV NS3/4a protease inhibitors.
Zn- And Cu-catalyzed coupling of tertiary alkyl bromides and oxalates to forge challenging C?O, C?S, and C?N bonds
Gong, Yuxin,Zhu, Zhaodong,Qian, Qun,Tong, Weiqi,Gong, Hegui
supporting information, p. 1005 - 1010 (2021/02/01)
We describe here the facile construction of sterically hindered tertiary alkyl ethers and thioethers via the Zn(OTf)2catalyzed coupling of alcohols/phenols with unactivated tertiary alkyl bromides and the Cu(OTf)2-catalyzed thiolation of unactivated tertiary alkyl oxalates with thiols. The present protocol represents one of the most effective unactivated tertiary C(sp3)? heteroatom bond-forming conditions via readily accessible Lewis acid catalysis that is surprisingly less developed.
Hepatitis C virus inhibitors
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Page/Page column 22, (2017/01/23)
Hepatitis C virus inhibitors having the general formula (I) are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
