Ravi P Nargund

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint The role of melanocortins in body weight regulation: opportunities for the treatment of obesity
    Douglas J MacNeil
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Eur J Pharmacol 440:141-57. 2002
  2. ncbi request reprint Melanocortin-4 receptor (MC4R) agonists for the treatment of obesity
    Ravi P Nargund
    Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    J Med Chem 49:4035-43. 2006
  3. doi request reprint Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity
    Shuwen He
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:4399-405. 2010
  4. doi request reprint Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity
    Jian Liu
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:2074-7. 2010
  5. doi request reprint Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist
    Shuwen He
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 20:2106-10. 2010
  6. ncbi request reprint The role of melanocortins in body weight regulation: opportunities for the treatment of obesity
    Douglas J MacNeil
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Eur J Pharmacol 450:93-109. 2002
  7. doi request reprint Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist
    Qingmei Hong
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 21:2330-4. 2011
  8. ncbi request reprint Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subt
    Zhixiong Ye
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 15:3501-5. 2005
  9. ncbi request reprint Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists
    Liangqin Guo
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:4895-900. 2010
  10. doi request reprint Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity
    Xiao Ming Guan
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Cell Metab 11:101-12. 2010

Collaborators

Detail Information

Publications28

  1. ncbi request reprint The role of melanocortins in body weight regulation: opportunities for the treatment of obesity
    Douglas J MacNeil
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Eur J Pharmacol 440:141-57. 2002
    ....
  2. ncbi request reprint Melanocortin-4 receptor (MC4R) agonists for the treatment of obesity
    Ravi P Nargund
    Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    J Med Chem 49:4035-43. 2006
  3. doi request reprint Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity
    Shuwen He
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:4399-405. 2010
    ..Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models...
  4. doi request reprint Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity
    Jian Liu
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:2074-7. 2010
    ..After oral administration, compound 9 had sufficient exposure in diet induced obese mice to demonstrate efficacy in lowering food intake and body weight via BRS-3 activation...
  5. doi request reprint Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist
    Shuwen He
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 20:2106-10. 2010
    ..Compound 1 shows excellent erectogenic activity in the rodent models...
  6. ncbi request reprint The role of melanocortins in body weight regulation: opportunities for the treatment of obesity
    Douglas J MacNeil
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Eur J Pharmacol 450:93-109. 2002
    ....
  7. doi request reprint Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist
    Qingmei Hong
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 21:2330-4. 2011
    ..Compound 1 shows anti-obesity efficacy without potentiating erectile activity in the rodent models...
  8. ncbi request reprint Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subt
    Zhixiong Ye
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 15:3501-5. 2005
    ..Its in vivo characterization revealed mechanism-based food intake reduction and erectile activity augmentation in rodents...
  9. ncbi request reprint Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists
    Liangqin Guo
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:4895-900. 2010
    ..Design, synthesis, and SAR of a series of 3H-spiro[isobenzofuran-1,4'-piperidine] based compounds as potent, selective and orally bioavailable melanocortin subtype-4 receptor (MC4R) agonists are disclosed...
  10. doi request reprint Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity
    Xiao Ming Guan
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Cell Metab 11:101-12. 2010
    ..These results demonstrate that BRS-3 has a role in energy homeostasis that complements several well-known pathways and that BRS-3 agonists represent a potential approach to the treatment of obesity...
  11. ncbi request reprint Optimization of a privileged structure leading to potent and selective human melanocortin subtype-4 receptor ligands
    Raman K Bakshi
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 16:1130-3. 2006
    ..Design and synthesis of potent MC4 selective agonists based on cyclohexylpiperidine derived cyclic urea, oxazolidinones, and sulfonamide based privileged structures are disclosed...
  12. ncbi request reprint Structure-activity relationship of linear tetrapeptides Tic-DPhe-Arg-Trp-NH2 at the human melanocortin-4 receptor and effects on feeding behaviors in rat
    Zhixiong Ye
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Peptides 26:2017-25. 2005
    ..Intracerebroventricular administration of peptide 10 induced significant inhibition of cumulative overnight food intake and feeding duration in rats...
  13. doi request reprint Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity
    Shuwen He
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:6524-32. 2010
    ..However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models...
  14. doi request reprint Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands
    Qingmei Hong
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 20:4483-6. 2010
    ..The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties...
  15. ncbi request reprint Melanocortin subtype 4 receptor agonists: structure-activity relationships about the 4-alkyl piperidine core
    Iyassu K Sebhat
    Department of Medicinal Chemistry, Merck and Co, Inc, PO Box, 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:5720-3. 2007
    ..SAR about the piperidine core in a series of MC4R agonists is described. A number of alkyl substituents that furnish compounds with good affinity and functional potency are reported...
  16. doi request reprint Antiobesity effect of MK-5046, a novel bombesin receptor subtype-3 agonist
    Xiao Ming Guan
    Department of Metabolic Disorders, Merck Research Laboratories, Rahway, New Jersey 07065 0900, USA
    J Pharmacol Exp Ther 336:356-64. 2011
    ..Our results demonstrate antiobesity efficacy for MK-5046 in rodents and dogs and further support BRS-3 agonism as a new approach to the treatment of obesity...
  17. ncbi request reprint 1-Amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid as a Tic mimetic: application in the synthesis of potent human melanocortin-4 receptor selective agonists
    Raman K Bakshi
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 15:3430-3. 2005
    ..The discovery of 1-amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid analogs as potent human melanocortin-4 selective agonists is described...
  18. ncbi request reprint 2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists
    Brenda L Palucki
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 15:1993-6. 2005
    ..The 5- and 6-alkylated piperazine compounds exhibit low bioactivation potential as measured by covalent binding in microsome preparations...
  19. doi request reprint The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization
    Harry R Chobanian
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem 20:2845-9. 2012
    ..This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature...
  20. doi request reprint Body temperature as a mouse pharmacodynamic response to bombesin receptor subtype-3 agonists and other potential obesity treatments
    Joseph M Metzger
    Departments of Pharmacology, Rahway, NJ 07065, USA
    Am J Physiol Endocrinol Metab 299:E816-24. 2010
    ..The T(b) assay is a robust, information-rich assay that is simpler and has a greater throughput than measuring metabolic rate and is a practical, effective tool for drug discovery...
  21. doi request reprint Synthesis and SAR of potent and orally bioavailable tert-butylpyrrolidine archetype derived melanocortin subtype-4 receptor modulators
    Liangqin Guo
    Department of Medicinal Chemistry, Merck Research Laboratories, 126 E Lincoln Avenue, PO Box 2000, RY 50G 332, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 18:3242-7. 2008
    ..Discovery of a series of tert-butyl pyrrolidine derived, potent and orally bioavailable melanocortin receptor subtype-4 (MC4R) selective modulators is disclosed...
  22. ncbi request reprint Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist
    Brenda L Palucki
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065 0900, USA
    Bioorg Med Chem Lett 15:171-5. 2005
    ..We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. Further in vivo development of lead agonist, MB243, is disclosed...
  23. ncbi request reprint Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist
    Iyassu K Sebhat
    Department of Chemistry, Merck and Co, Inc, P O Box 2000, Rahway, New Jersey 07065 0900, USA
    J Med Chem 45:4589-93. 2002
    ..Pharmacological testing confirms the food intake lowering effects of MC4R agonism and suggests another role for the receptor in the stimulation of erectile activity...
  24. ncbi request reprint Metabolic activation of a 1,3-disubstituted piperazine derivative: evidence for a novel ring contraction to an imidazoline
    George A Doss
    Department of Drug Metabolism, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    Chem Res Toxicol 18:271-6. 2005
    ..The resulting cysteinyl-glycine conjugate underwent subsequent hydrolysis of the glycine residue. Understanding of the mechanism of bioactivation led to the design of MB243 analogues that exhibited reduced covalent protein binding...
  25. pmc A role for the melanocortin 4 receptor in sexual function
    Lex H T Van der Ploeg
    Merck Research Laboratories, P O Box 2000, Rahway, NJ 07065, USA
    Proc Natl Acad Sci U S A 99:11381-6. 2002
    ..Our results provide a basis for the existence of MC4R-controlled neuronal pathways that control sexual function...
  26. doi request reprint Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists
    Shuwen He
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:1913-7. 2010
    ..This effort led to the discovery of compound 22e with significantly improved potency at both rodent and human BRS-3...
  27. doi request reprint Pyridinesulfonylureas and pyridinesulfonamides as selective bombesin receptor subtype-3 (BRS-3) agonists
    Michael M C Lo
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 21:2040-3. 2011
    ..We describe the discovery of 2a, which has mid-nanomolar potency, selectivity for human BRS-3 versus the other bombesin-like receptors, and good bioavailability...
  28. pmc Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists
    Irina D Pogozheva
    Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, USA
    Biochemistry 44:11329-41. 2005
    ....