Tetrazole and ester substituted tetrahydoquinoxalines as potent cholesteryl ester transfer protein inhibitors

Eary, C. Todd; Jones, Zachary S.; Groneberg, Robert D.; Burgess, Laurence E.; Mareska, David A.; Drew, Mark D.; Blake, James F.; Laird, Ellen R.; Balachari, Devan; O’Sullivan, Michael; Allen, Andrew C.; Marsh, Vivienne

doi:10.1016/j.bmcl.2007.01.112

Cited by 80 publications

(30 citation statements)

References 11 publications

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“…In particular, dihydroquinoxalinones constitute a prevailing scaffold frequently found in many biologically active natural and synthetic products ( Figure 1). Many examples are used as pharmaceuticals, including antiviral compounds, used for the treatment of HIV, 14 anticancer compounds, 15 cholesteryl ester transfer protein inhibitors, 16 antiinflammatory compounds, 17 antitumor agents, 18 and also as agrochemicals. 19 However, enantioselective approaches to the synthesis of chiral dihydroquinoxalin-2-ones are scarce and limited to catalytic asymmetric hydrogenations of quinoxalinones.…”

Section: Scheme 1 Enantioselective Photooxidative Mannich Reactionmentioning

confidence: 99%

A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones

et al. 2019

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An enantioselective photooxidative Mannich reaction of dihydroquinoxalinones with ketones by the merger of organophotoredox and asymmetric organocatalysis is described. This protocol features a very mild reaction conditions using simple and cheap catalysts (Eosin Y and (S)-Proline) for the synthesis of chiral quinoxaline derivatives with good to high yields (up to 94%) and excellent enantioselectivities (up to 99% ee).

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Section: Scheme 1 Enantioselective Photooxidative Mannich Reactionmentioning

confidence: 99%

A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones

et al. 2019

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“…Optically pure tetrahydroquinoxaline derivatives have shown great potential for pharmaceutical applications. For example, chiral compound A has been pursued as a potent vasopressin V2 receptor antagonists,1d and optically pure compound B is a promising inhibitor of cholesteryl ester transfer protein 1e. In both cases, the chirality of the compounds was found to play a very important role in the relevant bioactivity of these compounds…”

Section: Optimization Of the Reaction Conditions For Asymmetric Hydromentioning

confidence: 99%

Asymmetric Hydrogenation of Quinoxalines with Diphosphinite Ligands: A Practical Synthesis of Enantioenriched, Substituted Tetrahydroquinoxalines

et al. 2009

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“…However, other researchers contend that CETP has beneficial effects by facilitating cholesterol removal through the reverse cholesterol transport pathway. Although there continues to be debate on the issues surrounding CETP [ 1 , 2 , 3 , 4 , 5 ], various reversible and irreversible CETP inhibitors have already been reported [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Furthermore, Roche’s JTT-705 [ 10 ] and Merck’s anacetrapib [ 12 ] are both entering phase III clinical trials to treat Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease.…”

Section: Introductionmentioning

confidence: 99%

CoMFA, CoMSIA and Eigenvalue Analysis on Dibenzodioxepinone and Dibenzodioxocinone Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

Xiong

Zhao

et al. 2008

Molecules

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CoMFA, CoMSIA and eigenvalue analysis (EVA) were performed to study the structural features of 61 diverse dibenzodioxepinone and dibenzodioxocinone analogues to probe cholesteryl ester transfer protein (CETP) inhibitory activity. Three methods yielded statistically significant models upon assessment of cross-validation, bootstrapping, and progressive scrambling. This was further validated by an external set of 13 derivatives. Our results demonstrate that three models have a good interpolation as well as extrapolation. The hydrophobic features were confirmed to contribute significantly to inhibitor potencies, while a pre-oriented hydrogen bond provided by the hydroxyl group at the 3-position indicated a good correlation with previous SAR, and a hydrogen bond acceptor may play a crucial role in CETP inhibition. These derived models may help us to gain a deeper understanding of the binding interaction of these lactone-based compounds and aid in the design of new potent compounds against CETP.

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Tetrazole and ester substituted tetrahydoquinoxalines as potent cholesteryl ester transfer protein inhibitors

Cited by 80 publications

References 11 publications

A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones

A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones

Asymmetric Hydrogenation of Quinoxalines with Diphosphinite Ligands: A Practical Synthesis of Enantioenriched, Substituted Tetrahydroquinoxalines

CoMFA, CoMSIA and Eigenvalue Analysis on Dibenzodioxepinone and Dibenzodioxocinone Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

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