Hong C Shen

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint On the diastereoselectivity of ru-catalyzed [5 + 2] cycloadditions
    Barry M Trost
    Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
    Org Lett 5:4149-51. 2003
  2. doi request reprint Acyl hydroxypyrazoles as novel agonists for high-affinity nicotinic acid receptor GPR109A: WO2008051403
    Hong C Shen
    Research Fellow Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065 0900, USA
    Expert Opin Ther Pat 19:1149-55. 2009
  3. doi request reprint Novel patent publications on high-affinity nicotinic acid receptor agonists
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co Inc, 126 East Lincoln Avenue, Rahway, NJ 07065 0900, USA
    Expert Opin Ther Pat 19:957-67. 2009
  4. doi request reprint Discovery of spirocyclic secondary amine-derived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 19:3398-404. 2009
  5. doi request reprint Discovery of novel tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats
    Hong C Shen
    Departments of Medicinal Chemistry, Merck Research Laboratories, Merck and Co, Inc, Rahway, New Jersey 07065 0900, USA
    J Med Chem 52:2587-602. 2009
  6. doi request reprint Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement
    Hong C Shen
    Merck Research Laboratories, Merck and Co, Inc, Rahway, NJ 07065 0900, USA
    J Med Chem 52:5009-12. 2009
  7. doi request reprint Discovery of pyrazolopyrimidines as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co, Inc, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 18:4948-51. 2008
  8. ncbi request reprint Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 17:6723-8. 2007
  9. ncbi request reprint Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor
    Hong C Shen
    Merck Research Laboratories, Merck and Co, Inc, Rahway, New Jersey 07065 0900, USA
    J Med Chem 50:6303-6. 2007
  10. doi request reprint Discovery of 3,3-disubstituted piperidine-derived trisubstituted ureas as highly potent soluble epoxide hydrolase inhibitors
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 19:5314-20. 2009

Detail Information

Publications28

  1. ncbi request reprint On the diastereoselectivity of ru-catalyzed [5 + 2] cycloadditions
    Barry M Trost
    Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
    Org Lett 5:4149-51. 2003
    ..reaction: see text]. Ru-catalyzed cycloisomerization of cyclopropylenynes proceeds with good to high diastereoselectivities to form hexahydroazulenes...
  2. doi request reprint Acyl hydroxypyrazoles as novel agonists for high-affinity nicotinic acid receptor GPR109A: WO2008051403
    Hong C Shen
    Research Fellow Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065 0900, USA
    Expert Opin Ther Pat 19:1149-55. 2009
    ..The fused bicyclic core contains a hydroxypyrazole that mimics the anthranilide moiety described in their earlier patents and patent publications...
  3. doi request reprint Novel patent publications on high-affinity nicotinic acid receptor agonists
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co Inc, 126 East Lincoln Avenue, Rahway, NJ 07065 0900, USA
    Expert Opin Ther Pat 19:957-67. 2009
    ....
  4. doi request reprint Discovery of spirocyclic secondary amine-derived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 19:3398-404. 2009
    ..This study posed the question as to whether sEH inhibition provides a robust mechanism leading to a significant antihypertensive effect...
  5. doi request reprint Discovery of novel tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats
    Hong C Shen
    Departments of Medicinal Chemistry, Merck Research Laboratories, Merck and Co, Inc, Rahway, New Jersey 07065 0900, USA
    J Med Chem 52:2587-602. 2009
    ....
  6. doi request reprint Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement
    Hong C Shen
    Merck Research Laboratories, Merck and Co, Inc, Rahway, NJ 07065 0900, USA
    J Med Chem 52:5009-12. 2009
    ..With minimal off-target activity and a good PK profile, the benchmark 2d exhibited remarkable in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery...
  7. doi request reprint Discovery of pyrazolopyrimidines as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co, Inc, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 18:4948-51. 2008
    ..In addition to its intrinsic activity, compound 9n significantly enhances nicotinic acid binding to the receptor, thereby potentiating the functional efficacy of nicotinic acid...
  8. ncbi request reprint Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 17:6723-8. 2007
    ..Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin...
  9. ncbi request reprint Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor
    Hong C Shen
    Merck Research Laboratories, Merck and Co, Inc, Rahway, New Jersey 07065 0900, USA
    J Med Chem 50:6303-6. 2007
    ..Compound 2i exhibited good in vivo antilipolytic efficacy while providing a significantly improved therapeutic index over vasodilation (flushing) with respect to niacin in the mouse model...
  10. doi request reprint Discovery of 3,3-disubstituted piperidine-derived trisubstituted ureas as highly potent soluble epoxide hydrolase inhibitors
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 19:5314-20. 2009
    ..This observation further challenges the premise that sEH inhibition can provide a viable approach to the treatment of hypertensive patients...
  11. ncbi request reprint Alpha-heteroarylation of esters, lactones, amides, and lactams by nucleophilic aromatic substitution
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Company, Inc, P O Box 2000, Rahway, New Jersey 07065 0900, USA
    Org Lett 8:1447-50. 2006
    ..The choice of NaHMDS in toluene gave the best results. A tandem alpha-heteroarylation and hydroxylation protocol using air as the oxidant afforded tertiary alcohols in good yields...
  12. doi request reprint A strategy of employing aminoheterocycles as amide mimics to identify novel, potent and bioavailable soluble epoxide hydrolase inhibitors
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 19:5716-21. 2009
    ..The strategy of employing aminoheterocycles as amide replacements may represent a general approach to develop mimics of known hydrolase or protease inhibitors containing an amide moiety...
  13. doi request reprint Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co, Inc, Rahway, New Jersey 07065 0900, USA mail
    J Med Chem 53:2666-70. 2010
    ....
  14. doi request reprint Soluble epoxide hydrolase inhibitors: a patent review
    Hong C Shen
    Merck and Co, Inc, Merck Research Laboratories, Department of Medicinal Chemistry RY800 C114, 126 East Lincoln Avenue, PO Box 2000, Rahway, NJ 07065 0900, USA
    Expert Opin Ther Pat 20:941-56. 2010
    ..It has been claimed that sEH inhibitors can be used to treat hypertension, diabetes, stroke, dyslipidemia, pain, immunological disorders, eye diseases, neurological diseases and other indications...
  15. doi request reprint Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 21:1299-305. 2011
    ..Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed...
  16. doi request reprint Discovery of pyrazolyl propionyl cyclohexenamide derivatives as full agonists for the high affinity niacin receptor GPR109A
    Fa Xiang Ding
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 20:3372-5. 2010
    ..The structure-activity relationship (SAR) studies were aimed to improve activity on GPR109A, reduce Cytochrome P450 2C8 (CYP2C8) and Cytochrome P450 2C9 (CYP2C9) inhibition, reduce serum shift and improve pharmacokinetic (PK) profiles...
  17. doi request reprint Tetrahydro anthranilic acid as a surrogate for anthranilic acid: application to the discovery of potent niacin receptor agonists
    Subharekha Raghavan
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 18:3163-7. 2008
    ..Several compounds were identified that were potent against the niacin receptor, had enhanced cytochrome P450 selectivity against subtypes CYP2C8 and CYP2C9, and improved oral exposure in mice...
  18. doi request reprint Discovery of benzodihydroisofurans as novel, potent, bioavailable and brain-penetrant prolylcarboxypeptidase inhibitors
    Hong C Shen
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 22:1550-6. 2012
    ..In the established diet-induced obese (eDIO) mouse model, compound ent-3a displayed target engagement both in plasma and in brain. However, this compound failed to induce significant body weight loss in eDIO mice in a five-day study...
  19. doi request reprint The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors
    Thomas H Graham
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 22:658-65. 2012
    ..The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied...
  20. doi request reprint Synthesis and biological evaluation of platensimycin analogs
    Hong C Shen
    Departments of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 19:1623-7. 2009
    ..The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity...
  21. doi request reprint Palladium-catalyzed Suzuki-Miyaura coupling of pyridyl-2-boronic esters with aryl halides using highly active and air-stable phosphine chloride and oxide ligands
    David X Yang
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co, Inc, P O Box 2000, Rahway, New Jersey 07065 0900, USA
    Org Lett 11:381-4. 2009
    ..The convenient reaction protocol demonstrates its potentially wide applications in medicinal chemistry...
  22. ncbi request reprint Gold(I)-catalyzed regioselective cyclizations of silyl ketene amides and carbamates with alkynes
    Ellen C Minnihan
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co Inc, P O Box 2000, Rahway, NJ 07065, USA
    J Org Chem 72:6287-9. 2007
    ..The gold(I)-catalyzed regioselective cyclizations of silyl ketene amides or carbamates with alkynes were utilized to construct cyclopentanes or dehydro-delta-lactams...
  23. ncbi request reprint A formal [3 + 3] cycloaddition reaction. Improved reactivity using alpha,beta-unsaturated iminium salts and evidence for reversibility of 6pi-electron electrocyclic ring closure of 1-oxatrienes
    Hong C Shen
    Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Org Chem 68:1729-35. 2003
    ..Most significantly, experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6pi-electron electrocyclic ring-closure of 1-oxatrienes...
  24. ncbi request reprint An enantioselective biomimetic total synthesis of (-)-siccanin
    Barry M Trost
    Department of Chemistry, Stanford University, Stanford, CA 94305 5080, USA
    Angew Chem Int Ed Engl 42:3943-7. 2003
  25. ncbi request reprint Synthesis of chiral chromans by the Pd-catalyzed asymmetric allylic alkylation (AAA): scope, mechanism, and applications
    Barry M Trost
    Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
    J Am Chem Soc 126:11966-83. 2004
    ....
  26. ncbi request reprint Biomimetic enantioselective total synthesis of (-)-siccanin via the Pd-catalyzed asymmetric allylic alkylation (AAA) and sequential radical cyclizations
    Barry M Trost
    Department of Chemistry, Stanford University, Stanford, California 94305 5080, USA
    J Am Chem Soc 126:12565-79. 2004
    ..These studies may shed light on the biosynthesis of this novel family of compounds...
  27. ncbi request reprint Syntheses of seven-membered rings: ruthenium-catalyzed intramolecular [5+2] cycloadditions
    Barry M Trost
    Department of Chemistry, Stanford University, Stanford, CA 94305 5080, USA
    Chemistry 11:2577-90. 2005
    ..The potential power of this methodology towards natural product total synthesis is demonstrated by the formation of several polycyclic systems with the chosen reaction conditions and readily available cyclopropylenyne substrates...
  28. ncbi request reprint A synthesis of trisubstituted alkenes by a Ru-catalyzed addition
    Barry M Trost
    Department of Chemistry, Stanford University Stanford, CA 94305 5080, USA
    Chemistry 8:2341-9. 2002
    ..The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes...