945724-02-7Relevant articles and documents
Discovery of Chromane Containing Hepatitis C Virus (HCV) NS5A Inhibitors with Improved Potency against Resistance-Associated Variants
Yu, Wensheng,Tong, Ling,Hu, Bin,Zhong, Bin,Hao, Jinglai,Ji, Tao,Zan, Shuai,Coburn, Craig A.,Selyutin, Oleg,Chen, Lei,Rokosz, Laura,Agrawal, Sony,Liu, Rong,Curry, Stephanie,McMonagle, Patricia,Ingravallo, Paul,Asante-Appiah, Ernest,Chen, Shiying,Kozlowski, Joseph A.
, p. 10228 - 10243 (2016/12/07)
The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/protein complexes for rational inhibitor design. As part of ongoing efforts on HCV NS5A inhibition at Merck, we now describe the discovery of a novel series of chromane containing NS5A inhibitors. SAR studies around the "Z" group of the tetracyclic indole scaffold explored fused bicyclic rings as alternates to the phenyl group of elbasvir (1, MK-8742) and identified novel chromane and 2,3-dihydrobenzofuran derivatives as "Z" group replacements offered good potency across all genotypes. This effort, incorporating the C-1 fluoro substitution at the tetracyclic indole core, led to the discovery of a new series of NS5A inhibitors, such as compounds 14 and 25-28, with significantly improved potency against resistance-associated variants, such as GT2b, GT1a Y93H, and GT1a L31V. Compound 14 also showed reasonable PK exposures in preclinical species (rat and dog).
A facile and general approach to 3-((trifluoromethyl)thio)-4 H -chromen-4-one
Xiang, Haoyue,Yang, Chunhao
supporting information, p. 5686 - 5689 (2015/02/19)
A facile and efficient synthetic strategy to 3-((trifluoromethyl)thio)-4H-chromen-4-one was developed. AgSCF3 and trichloroisocyanuric acid were employed here to generate active electrophilic trifluoromethylthio species in situ. This reaction could proceed under mild conditions in a short reaction time and be insensitive to air and moisture.
ANTIVIRAL COMPOUNDS
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Page/Page column 629, (2012/06/01)
The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
Hepatitis C Virus Inhibitors
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, (2009/08/18)
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
CHROMANE ANTAGONIST OF THE H-3 RECEPTOR
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Page/Page column 21-22, (2008/06/13)
This invention is directed to a compound of formula (I), as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula (I), a process of preparation of a compound of formula (I), a method of treatment of a disorder or condition that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula (I) as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit hyperactivity disorder (ADHD), psychotic disorders, cognitive disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the GI tract, hyper and hypo motility and acidic secretion of the gastro-intestinal tract, the method comprising administering to a mammal in need of such treatment a compound of formula (I) as described above.
