Christopher D Cox

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint Discovery of allosteric inhibitors of kinesin spindle protein (KSP) for the treatment of taxane-refractory cancer: MK-0731 and analogs
    Christopher D Cox
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Anticancer Agents Med Chem 10:697-712. 2010
  2. doi request reprint Conformational analysis of N,N-disubstituted-1,4-diazepane orexin receptor antagonists and implications for receptor binding
    Christopher D Cox
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 19:2997-3001. 2009
  3. doi request reprint 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 insomnia
    Christopher 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
  4. ncbi request reprint 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 KSP
    Christopher 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
  5. ncbi request reprint 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 KSP
    Christopher 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
  6. ncbi request reprint 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-glycoprotein
    Christopher 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
  7. doi request reprint 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 can
    Christopher 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
  8. doi request reprint 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 properties
    Paul 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
  9. ncbi request reprint 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 KSP
    Paul 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
  10. doi request reprint Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomnia
    Christopher J Winrow
    Neuroscience Department, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
    Neuropharmacology 62:978-87. 2012

Detail Information

Publications19

  1. ncbi request reprint Discovery of allosteric inhibitors of kinesin spindle protein (KSP) for the treatment of taxane-refractory cancer: MK-0731 and analogs
    Christopher D Cox
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Anticancer Agents Med Chem 10:697-712. 2010
    ....
  2. doi request reprint Conformational analysis of N,N-disubstituted-1,4-diazepane orexin receptor antagonists and implications for receptor binding
    Christopher 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...
  3. doi request reprint 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 insomnia
    Christopher 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
    ....
  4. ncbi request reprint 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 KSP
    Christopher 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...
  5. ncbi request reprint 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 KSP
    Christopher 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...
  6. ncbi request reprint 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-glycoprotein
    Christopher 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...
  7. doi request reprint 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 can
    Christopher 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...
  8. doi request reprint 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 properties
    Paul 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...
  9. ncbi request reprint 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 KSP
    Paul 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...
  10. doi request reprint Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomnia
    Christopher 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'...
  11. doi request reprint Design and synthesis of conformationally constrained N,N-disubstituted 1,4-diazepanes as potent orexin receptor antagonists
    Paul 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...
  12. doi request reprint Discovery of 3,9-diazabicyclo[4.2.1]nonanes as potent dual orexin receptor antagonists with sleep-promoting activity in the rat
    Paul 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...
  13. doi request reprint Discovery of a potent, CNS-penetrant orexin receptor antagonist based on an n,n-disubstituted-1,4-diazepane scaffold that promotes sleep in rats
    David 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...
  14. doi request reprint Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist
    Christopher 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...
  15. doi request reprint The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey
    Sean 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'...
  16. doi request reprint Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia
    Izzat 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...
  17. ncbi request reprint Discovery of dual orexin receptor antagonists (DORAs) for the treatment of insomnia
    Paul 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
    ....
  18. ncbi request reprint Total synthesis of lactonamycinone
    Tony Siu
    Department of Chemistry, Columbia University, Havemeyer Hall, New York, NY 10 021, USA
    Angew Chem Int Ed Engl 42:5629-34. 2003
  19. ncbi request reprint Studies directed toward the total synthesis of lactonamycin: control of the sense of cycloaddition of a quinone through directed intramolecular catalysis
    Christopher D Cox
    Department of Chemistry, Columbia University, New York, NY 10021, USA
    Angew Chem Int Ed Engl 42:5625-9. 2003