108833-49-4Relevant articles and documents
Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants
Matthew, Ashley N.,Zephyr, Jacqueto,Hill, Caitlin. J.,Jahangir, Muhammad,Newton, Alicia,Petropoulos, Christos J.,Huang, Wei,Kurt-Yilmaz, Nese,Schiffer, Celia A.,Ali, Akbar
, p. 5699 - 5716 (2017)
A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156, and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC50 values ≤5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.
Hepatitis C virus inhibitors
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Page/Page column 593, (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.
TRIAZOLOPYRAZINE DERIVATIVES AND THEIR USE FOR TREATING NEUROLOGICAL AND PSYCHIATRIC DISORDERS
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Page/Page column 20; 21, (2013/03/26)
The present invention is directed to triazolopyrazine compounds of Formula (I). Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds as therapeutic agents treating neurological and psychiatric disorders.
COMPOUNDS FOR THE TREATMENT OF MULTI-DRUG RESISTANT BACTERIAL INFECTIONS
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Page/Page column 141, (2010/11/25)
The present invention relates to compounds that demonstrate antibacterial activity, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans. In particular this invention relates to compounds useful for the treatment of bacterial infections in warm-blooded animals such as humans, more particularly to the use of these compounds in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans.
Synthesis of substituted 1,3-dimethyl-1H-quinoxalin-2-ones from aniline derivatives
Li, Xun,Wang, Donghua,Wu, Jifeng,Xu, Wenfang
, p. 2741 - 2751 (2007/10/03)
Substituted 1,3-dimethyl-1H-quinoxalin-2-ones (7) have been synthesized through the procedures of acylation, nitration, reduction, intramolecular alkylation, oxidation, and N-methylation starting from 3,4-disubstituted aniline.
Novel approach to 3-methyl-1H-quinoxalin-2-ones
Li, Xun,Wang, Donghua,Wu, Jifeng,Xu, Wenfang
, p. 2553 - 2560 (2007/10/03)
A novel approach to the synthesis of 3-methyl-1H-quinoxalin-2-ones has been described. These compounds were regioselectively prepared by starting from substituted phenylamines and α-chloropropionyl chloride through the efficient procedures of acylation, nitration, reduction, intramolecular alkylation, and oxidation. Copyright Taylor & Francis, Inc.
