Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV polymerase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 2, 2008, Pages 568-570

  Bosse, Todd D ^a   Larson, Daniel P ^a   Wagner, Rolf ^a   Hutchinson, Doug K ^a   Rockway, Todd W ^a   Kati, Warren M ^a   Liu, Yaya ^a   Masse, Sherie ^a   Middleton, Tim ^a   Mo, Hongmei ^a   Montgomery, Debra ^a   Jiang, Wen ^a   Koev, Gennadiy ^a   Kempf, Dale J ^a   Molla, Akhter ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Benzothiadiazines; HCV; Hepatitis; Inhibitors; Naphthalenones; Polymerase

Indexed keywords

ANTIVIRUS AGENT; ENZYME INHIBITOR; NAPHTHALENONE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CELL ASSAY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; GENOTYPE; HEPATITIS C VIRUS; NONHUMAN; STRUCTURE ACTIVITY RELATION; VIRUS INHIBITION;

DNA-DIRECTED RNA POLYMERASES; ENZYME INHIBITORS; GENOTYPE; HEPACIVIRUS; NAPHTHALENES; STRUCTURE-ACTIVITY RELATIONSHIP;

HEPATITIS C VIRUS;

EID: 38149112738     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.11.088     Document Type: Article

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6. All compounds discussed in this publication were prepared as the racemic mixture. Enantiomerically pure compounds were prepared at a later date and will be discussed in future publications.
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8. All vinyl halides were commercially available except 1-iodo-3,3-dimethyl-butane, 1-bromo-5,5-dimethyl-hex-2-ene, and (3-bromo-propenyl)-cyclohexane. 1-Iodo-3,3-dimethyl-butane was made by conversion of the hydroxyl group of 3,3-dimethyl-butan-1-ol with iodine, triphenylphosphine, and imidazole in dichloroethane. 1-Bromo-5,5-dimethyl-hex-2-ene was made by reacting 3,3-dimethyl-butyraldehyde with vinylmagnesium bromide to give 5,5-dimethyl-hex-1-en-3-ol, which was then reacted with 1,5-hexadiene and thionyl bromide to yield the desired vinyl bromide. (3-bromo-propenyl)-cyclohexane was synthesized using the same procedure described for 1-bromo-5,5-dimethyl-hex-2-ene.
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