Discovery of MK-4409, a Novel Oxazole FAAH Inhibitor for the Treatment of Inflammatory and Neuropathic Pain.

Autor: Chobanian HR; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Guo Y; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Liu P; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Chioda MD; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Fung S; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Lanza TJ; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Chang L; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Bakshi RK; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Dellureficio JP; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Hong Q; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., McLaughlin M; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Belyk KM; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Krska SW; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Makarewicz AK; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Martel EJ; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Leone JF; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Frey L; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Karanam B; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Madeira M; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Alvaro R; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Shuman J; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Salituro G; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Terebetski JL; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Jochnowitz N; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Mistry S; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., McGowan E; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Hajdu R; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Rosenbach M; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Abbadie C; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Alexander JP; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Shiao LL; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Sullivan KM; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Nargund RP; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Wyvratt MJ; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., Lin LS; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States., DeVita RJ; Departments of Medicinal Chemistry, Process Chemistry, Drug Metabolism and Pharmacokinetics, Preclinical Development, Pharmacology, and Immunology, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.

Publikováno v: ACS medicinal chemistry letters [ACS Med Chem Lett] 2014 Apr 10; Vol. 5 (6), pp. 717-21. Date of Electronic Publication: 2014 Apr 10 (Print Publication: 2014).

Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists.

Autor: Guo L; Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. liangqin_guo@merck.com, Ye Z, Liu J, He S, Bakshi RK, Sebhat IK, Dobbelaar PH, Hong Q, Jian T, Dellureficio JP, Tsou NN, Ball RG, Weinberg DH, MacNeil T, Tang R, Tamvakopoulos C, Peng Q, Chen HY, Chen AS, Martin WJ, MacIntyre DE, Strack AM, Fong TM, Wyvratt MJ, Nargund RP

Publikováno v: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Aug 15; Vol. 20 (16), pp. 4895-900. Date of Electronic Publication: 2010 Jun 17.

Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist.

Autor: He S; Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. shuwen_he@merck.com, Ye Z, Dobbelaar PH, Sebhat IK, Guo L, Liu J, Jian T, Lai Y, Franklin CL, Bakshi RK, Dellureficio JP, Hong Q, Tsou NN, Ball RG, Cashen DE, Martin WJ, Weinberg DH, Macneil T, Tang R, Tamvakopoulos C, Peng Q, Miller RR, Stearns RA, Chen HY, Chen AS, Strack AM, Fong TM, Macintyre DE, Wyvratt MJ Jr, Nargund RP

Publikováno v: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Apr 01; Vol. 20 (7), pp. 2106-10. Date of Electronic Publication: 2010 Feb 19.