Journal ArticleDOI
Identification of a potent and metabolically stable series of fluorinated diphenylpyridylethanamine-based cholesteryl ester transfer protein inhibitors.
Michael M. Miller,Yalei Liu,Ji Jiang,James A. Johnson,Muthoni G. Kamau,David S. Nirschl,Yufeng Wang,Lalgudi S. Harikrishnan,David S. Taylor,Alice Ye A. Chen,Xiaohong Yin,Ramakrishna Seethala,Tara L. Peterson,Tatyana Zvyaga,Jun Zhang,Christine Huang,Ruth R. Wexler,Michael A. Poss,R. Michael Lawrence,Leonard P. Adam,Mark E. Salvati +20 more
TLDR
A novel series of diphenylpyridylethanamine-based inhibitors of cholesteryl ester transfer protein is described, and optimization of the urea moiety is explored to balance in vitro metabolic stability with CETP potency in the whole plasma assay.About:
This article is published in Bioorganic & Medicinal Chemistry Letters.The article was published on 2012-10-15. It has received 19 citations till now. The article focuses on the topics: Cholesterylester transfer protein & Sterol O-acyltransferase.read more
Citations
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Journal ArticleDOI
Applications of Fluorine in Medicinal Chemistry
TL;DR: The effects of the strategic incorporation of fluorine in drug molecules and applications in positron emission tomography are provided, as well as new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds.
Journal ArticleDOI
Trifluoromethyl nitrogen heterocycles: synthetic aspects and potential biological targets
TL;DR: Recent advances regarding the synthetic chemistry of fluorinated aziridine, azetidines, pyrrolidines and their lactam/amino acid counterparts are presented.
Journal ArticleDOI
Quantitative Assessment of the Impact of Fluorine Substitution on P-Glycoprotein (P-gp) Mediated Efflux, Permeability, Lipophilicity, and Metabolic Stability
Martin Pettersson,Xinjun Hou,Max Kuhn,Travis T. Wager,Gregory W. Kauffman,Patrick Robert Verhoest +5 more
TL;DR: In this article, the effect of introducing fluorine on the risk of encountering P-glycoprotein mediated efflux (as measured by MDR efflux ratio), passive permeability, lipophilicity, and metabolic stability was examined.
Journal ArticleDOI
Update on the discovery and development of cholesteryl ester transfer protein inhibitors for reducing residual cardiovascular risk.
TL;DR: This perspective will summarize recent events, new research developments, and the discovery of new classes of CETP inhibitors that have advanced to phase 3 cardiovascular outcome clinical trials and been terminated.
Journal ArticleDOI
Last of the gem-Difluorocycloalkanes: Synthesis and Characterization of 2,2-Difluorocyclobutyl-Substituted Building Blocks.
Anton V. Chernykh,Kostiantyn P. Melnykov,Kostiantyn P. Melnykov,Nataliya A. Tolmacheva,Ivan S. Kondratov,Dmytro S. Radchenko,Dmytro S. Radchenko,Constantin G. Daniliuc,Dmitriy M. Volochnyuk,Dmitriy M. Volochnyuk,Sergey V. Ryabukhin,Sergey V. Ryabukhin,Yuliya O. Kuchkovska,Yuliya O. Kuchkovska,Oleksandr O. Grygorenko,Oleksandr O. Grygorenko +15 more
TL;DR: An efficient approach to synthesis of previously unavailable 2-substituted difluorocyclobutane building blocks was developed and applied on a multigram scale and the key step included deoxofluorination of O-protected 2-(hydroxylmethyl)cyclobutanone.
References
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Journal ArticleDOI
Lipid Alterations and Decline in the Incidence of Coronary Heart Disease in the Helsinki Heart Study
Vesa Manninen,M. Olli Elo,M. Heikki Frick,Kauko Haapa,Olli P. Heinonen,Pertti Heinsalmi,Pekka Helo,Jussi K. Huttunen,Pertti Kaitaniemi,Pekka Koskinen,Hanna Mäenpää,Marjatta Mälkönen,Matti Mänttäri,Seppo Norola,Amos Pasternack,Jarmo Pikkarainen,Matti Romo,Tom Sjöblom,Esko A. Nikkilä +18 more
TL;DR: The results of this study suggest that both elevating HDL and lowering LDL cholesterol levels are effective in the primary prevention of CHD.
Journal Article
The Prediction of Human Pharmacokinetic Parameters from Preclinical and In Vitro Metabolism Data
TL;DR: This retrospective analysis has identified several approaches by which human pharmacokinetic data can be predicted from preclinical data and/or in vitro metabolism data that should find utility in the drug discovery and development processes in the identification and selection of compounds that will possess appropriate pharmacokinetics characteristics in humans for progression to clinical trials.
Journal ArticleDOI
Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial.
Sander J. Robins,Dorothea Collins,Janet Wittes,Vasilios Papademetriou,Prakash Deedwania,Ernst J. Schaefer,Judith R. McNamara,Moti L. Kashyap,Jerome M. Hershman,Laura F. Wexler,Hanna Bloomfield Rubins +10 more
TL;DR: Concentrations of LDL-C achieved with gemfibrozil treatment predicted a significant reduction in CHD events in patients with low HDL-C levels, however, the change in HDL- C levels only partially explained the beneficial effect of gem fibroZil.
Journal ArticleDOI
Cholesteryl Ester Transfer Protein: A Novel Target for Raising HDL and Inhibiting Atherosclerosis
Philip J. Barter,H. Bryan Brewer,M. John Chapman,Charles H. Hennekens,Daniel J. Rader,Alan R. Tall +5 more
TL;DR: Small-molecule inhibitors of CETP have now been tested in human subjects and shown to increase the concentration of HDL cholesterol while decreasing that of LDL cholesterol and apoB, and test the hypothesis in randomized trials of humans that pharmacological inhibition of CETp retards the development of atherosclerosis.
Related Papers (5)
Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis.
Mark Trinder,Yanan Wang,Christian M. Madsen,Christian M. Madsen,Tatjana Ponomarev,Lubos Bohunek,Brendan A. Daisely,HyeJin Julia Kong,Lisanne L. Blauw,Børge G. Nordestgaard,Anne Tybjærg-Hansen,Mark M. Wurfel,James A. Russell,James A. Russell,Keith R. Walley,Keith R. Walley,Patrick C.N. Rensen,John H. Boyd,Liam R. Brunham +18 more