Research Topics
| Christopher D CoxSummaryAffiliation: Merck Research Laboratories Country: USA Publications
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Publications
Conformational analysis of N,N-disubstituted-1,4-diazepane orexin receptor antagonists and implications for receptor bindingChristopher D Cox
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
Bioorg Med Chem Lett 19:2997-3001. 2009..Synthesis and evaluation of a macrocycle that enforces a similar conformation suggest that this geometry mimics the bioactive conformation...
Discovery of allosteric inhibitors of kinesin spindle protein (KSP) for the treatment of taxane-refractory cancer: MK-0731 and analogsChristopher D Cox
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
Anticancer Agents Med Chem 10:697-712. 2010....- Discovery of the dual orexin receptor antagonist [(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomniaChristopher D Cox
Department of Medicinal Chemistry, Merck Research Laboratories, P O Box 4, Sumneytown Pike, West Point, Pennsylvania 19486, USA
J Med Chem 53:5320-32. 2010.... - Kinesin spindle protein (KSP) inhibitors. Part 1: The discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of the mitotic kinesin KSPChristopher D Cox
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA
Bioorg Med Chem Lett 15:2041-5. 2005..X-ray crystallographic evidence is presented which demonstrates that these inhibitors bind in an allosteric pocket of KSP distant from the nucleotide and microtubule binding sites... - Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSPChristopher D Cox
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA
Bioorg Med Chem Lett 16:3175-9. 2006..This change led to a second generation compound with increased potency, a 400-fold enhancement in aqueous solubility at pH 4, and improved dog pharmacokinetics relative to the first generation compound... - Kinesin spindle protein (KSP) inhibitors. Part V: discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by beta-fluorination to overcome cellular efflux by P-glycoproteinChristopher D Cox
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA
Bioorg Med Chem Lett 17:2697-702. 2007..The discovery that cellular efflux by Pgp can be overcome by carefully modulating the basicity of an amine may be of general use to medicinal chemists attempting to transform leading compounds into cancer cell- or CNS-penetrant drugs... - Kinesin spindle protein (KSP) inhibitors. 9. Discovery of (2S)-4-(2,5-difluorophenyl)-n-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the treatment of taxane-refractory canChristopher D Cox
Department of Medicinal Chemistry, Merck Research Laboratories, P O Box 4, Sumneytown Pike, West Point, Pennsylvania 19486, USA
J Med Chem 51:4239-52. 2008..Compound 30 (MK-0731) was recently studied in a phase I clinical trial in patients with taxane-refractory solid tumors... - Discovery of [(2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl][5-methyl-2-(pyrimidin-2-yl)phenyl]methanone (MK-6096): a dual orexin receptor antagonist with potent sleep-promoting propertiesPaul J Coleman
Department of Medicinal Chemistry, Merck Research Laboratories, P O Box 4, Sumneytown Pike, West Point, PA 19486, USA
ChemMedChem 7:415-24, 337. 2012..DORA 28 (MK-6096) has exceptional in vivo activity in preclinical sleep models, and has advanced into phase II clinical trials for the treatment of insomnia... - Kinesin spindle protein (KSP) inhibitors. Part 6: Design and synthesis of 3,5-diaryl-4,5-dihydropyrazole amides as potent inhibitors of the mitotic kinesin KSPPaul J Coleman
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA
Bioorg Med Chem Lett 17:5390-5. 2007..Careful adjustment of amine basicity was essential for preserving cellular potency in a multidrug resistant cell line while maintaining good aqueous solubility... - Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomniaChristopher J Winrow
Neuroscience Department, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
Neuropharmacology 62:978-87. 2012..This mechanism is distinct from current standard of care such that MK-6096 represents a novel and selective therapeutic for the treatment of insomnia. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'... - Design and synthesis of conformationally constrained N,N-disubstituted 1,4-diazepanes as potent orexin receptor antagonistsPaul J Coleman
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA
Bioorg Med Chem Lett 20:2311-5. 2010..The design of these constrained analogs was guided by an understanding of the preferred solution and solid state conformation of the diazepane central ring... - Discovery of 3,9-diazabicyclo[4.2.1]nonanes as potent dual orexin receptor antagonists with sleep-promoting activity in the ratPaul J Coleman
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, United States
Bioorg Med Chem Lett 20:4201-5. 2010..In this Letter, we describe the synthesis of constrained diazepanes having a 3,9 diazabicyclo[4.2.1]nonane bicyclic core with good oral bioavailability and sleep-promoting activity in a rat EEG model... - Discovery of a potent, CNS-penetrant orexin receptor antagonist based on an n,n-disubstituted-1,4-diazepane scaffold that promotes sleep in ratsDavid B Whitman
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, WP14 2, West Point, PA 19486, USA
ChemMedChem 4:1069-74. 2009..In telemetry-implanted rats, oral administration of this antagonist produced a decrease in wakefulness, while increasing REM and non-REM sleep... - Promotion of sleep by suvorexant-a novel dual orexin receptor antagonistChristopher J Winrow
Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
J Neurogenet 25:52-61. 2011..Consistent cross-species sleep/wake architecture changes produced by Suvorexant highlight a unique opportunity to develop dual orexin antagonists as a novel therapy for insomnia... - The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkeySean M Smith
Neuroscience, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
Neuropharmacology 64:215-23. 2013..This article is part of a Special Issue entitled 'Cognitive Enhancers'... - Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophreniaIzzat T Raheem
Discovery Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
Bioorg Med Chem Lett 22:5903-8. 2012..Further, THPP-1 displays significantly fewer preclinical adverse events in assays measuring prolactin secretion, catalepsy, and weight gain, in contrast to the typical and atypical antipsychotics haloperidol and olanzapine... - Discovery of dual orexin receptor antagonists (DORAs) for the treatment of insomniaPaul J Coleman
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA
Curr Top Med Chem 11:696-725. 2011.... - Total synthesis of lactonamycinoneTony Siu
Department of Chemistry, Columbia University, Havemeyer Hall, New York, NY 10 021, USA
Angew Chem Int Ed Engl 42:5629-34. 2003 - Studies directed toward the total synthesis of lactonamycin: control of the sense of cycloaddition of a quinone through directed intramolecular catalysisChristopher D Cox
Department of Chemistry, Columbia University, New York, NY 10021, USA
Angew Chem Int Ed Engl 42:5625-9. 2003