J E Macor

Summary

Affiliation: Bristol-Myers Squibb
Country: USA

Publications

  1. ncbi request reprint The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist
    J E Macor
    AstraZeneca, Three Biotech, Worcester, MA 01605, USA
    Bioorg Med Chem Lett 11:319-21. 2001
  2. ncbi request reprint Stereoselective synthesis of new conformationally restricted analogues of a potent CGRP receptor antagonist
    Dmitry Zuev
    Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 5100, Wallingford, Connecticut 06492, USA
    Org Lett 7:2465-8. 2005
  3. ncbi request reprint A chiral synthesis of (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'- oxazolidin-2'-one]: a conformationally restricted analogue of acetylcholine that is a potent and selective alpha7 nicotinic receptor agonist
    John E Macor
    CNS Discovery, AstraZeneca, 1800 Concord Pike, Wilmington, Delaware 19850 5437, USA
    J Org Chem 69:6493-5. 2004
  4. ncbi request reprint N-3-substituted imidazoquinazolinones: potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction
    D P Rotella
    Discovery Chemistry and Cardiovascular Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 5400, Princeton, New Jersey 08543 5400, USA
    J Med Chem 43:1257-63. 2000
  5. ncbi request reprint The discovery of novel, potent and selective PDE5 inhibitors
    Y Bi
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 11:2461-4. 2001
  6. ncbi request reprint Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors
    D P Rotella
    Departments of Discovery Chemistry and Metabolic and Cardiovascular Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 5400, Princeton, New Jersey 08543 5400, USA
    J Med Chem 43:5037-43. 2000
  7. doi request reprint Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): a potent antagonist of the human calcitonin gene-related peptid
    Andrew P Degnan
    Department of Neuroscience Chemistry, Bristol Myers Squibb Research and Development, Wallingford, Connecticut 06492, USA
    J Med Chem 51:4858-61. 2008
  8. doi request reprint Catalytic asymmetric syntheses of tyrosine surrogates
    Xiaojun Han
    Neuroscience Discovery Chemistry, Research and Development, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Org Chem 73:8502-10. 2008
  9. doi request reprint Catalytic asymmetric syntheses of alpha-amino and alpha-hydroxyl acid derivatives
    Xiaojun Han
    Neuroscience Discovery Chemistry, Research and Development, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Org Chem 74:3993-6. 2009
  10. doi request reprint Carbamates as potent calcitonin gene-related peptide antagonists with improved solution stability
    Andrew P Degnan
    Neuroscience Discovery Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492 7660, USA
    Bioorg Med Chem Lett 19:3555-8. 2009

Detail Information

Publications38

  1. ncbi request reprint The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist
    J E Macor
    AstraZeneca, Three Biotech, Worcester, MA 01605, USA
    Bioorg Med Chem Lett 11:319-21. 2001
    ..Quinuclidine analogues (1 and 2) of tropisetron were also found to be potent and selective partial agonists at alpha7 nicotinic receptors...
  2. ncbi request reprint Stereoselective synthesis of new conformationally restricted analogues of a potent CGRP receptor antagonist
    Dmitry Zuev
    Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 5100, Wallingford, Connecticut 06492, USA
    Org Lett 7:2465-8. 2005
    ..The new diastereoselective LDA-promoted alpha-nitration of intermediate lactams established the required trans-configuration in the desired products...
  3. ncbi request reprint A chiral synthesis of (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'- oxazolidin-2'-one]: a conformationally restricted analogue of acetylcholine that is a potent and selective alpha7 nicotinic receptor agonist
    John E Macor
    CNS Discovery, AstraZeneca, 1800 Concord Pike, Wilmington, Delaware 19850 5437, USA
    J Org Chem 69:6493-5. 2004
    ....
  4. ncbi request reprint N-3-substituted imidazoquinazolinones: potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction
    D P Rotella
    Discovery Chemistry and Cardiovascular Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 5400, Princeton, New Jersey 08543 5400, USA
    J Med Chem 43:1257-63. 2000
    ..This paper describes the discovery of 14, a PDE5 inhibitor with improved potency and selectivity in vitro compared to sildenafil. This compound shows activity in a functional assay of erectile function comparable to that of sildenafil...
  5. ncbi request reprint The discovery of novel, potent and selective PDE5 inhibitors
    Y Bi
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 11:2461-4. 2001
    ..Compound 3a was more potent (PDE5 IC50=0.31 nM) and selective (>10,000-fold vs PDE1 and 160-fold selective vs PDE6) PDE5 inhibitor than sildenafil...
  6. ncbi request reprint Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitors
    D P Rotella
    Departments of Discovery Chemistry and Metabolic and Cardiovascular Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 5400, Princeton, New Jersey 08543 5400, USA
    J Med Chem 43:5037-43. 2000
    ..The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described...
  7. doi request reprint Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): a potent antagonist of the human calcitonin gene-related peptid
    Andrew P Degnan
    Department of Neuroscience Chemistry, Bristol Myers Squibb Research and Development, Wallingford, Connecticut 06492, USA
    J Med Chem 51:4858-61. 2008
    ..Compound 4 has good intranasal bioavailability in rabbits and shows dose-dependent activity in validated in vivo and ex vivo migraine models...
  8. doi request reprint Catalytic asymmetric syntheses of tyrosine surrogates
    Xiaojun Han
    Neuroscience Discovery Chemistry, Research and Development, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Org Chem 73:8502-10. 2008
    ..6% ee) and in good overall chemical yields. The key step in the sequence was the Burk's [Rh(COD)(2R,5R)-Et-DuPhos]BF4-catalyzed asymmetric hydrogenation of enamides with a variety of reactive functional groups...
  9. doi request reprint Catalytic asymmetric syntheses of alpha-amino and alpha-hydroxyl acid derivatives
    Xiaojun Han
    Neuroscience Discovery Chemistry, Research and Development, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Org Chem 74:3993-6. 2009
    ....
  10. doi request reprint Carbamates as potent calcitonin gene-related peptide antagonists with improved solution stability
    Andrew P Degnan
    Neuroscience Discovery Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492 7660, USA
    Bioorg Med Chem Lett 19:3555-8. 2009
    ..It was shown to retain excellent aqueous solubility (>50mg/mL, pH 7) while dramatically improving solution stability as compared to our previously disclosed development candidate, BMS-694153 (1)...
  11. doi request reprint In vitro intrinsic clearance-based optimization of N3-phenylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists
    Richard A Hartz
    Research and Development, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Med Chem 52:4161-72. 2009
    ..This led to the discovery of compound 12x, a highly potent (IC(50) = 1.0 nM) and selective CRF(1) receptor antagonist with good oral bioavailability (F = 52%) in rats and efficacy in the defensive withdrawal anxiety test in rats...
  12. doi request reprint Synthesis, structure-activity relationships, and in vivo evaluation of N3-phenylpyrazinones as novel corticotropin-releasing factor-1 (CRF1) receptor antagonists
    Richard A Hartz
    Research and Development, Bristol Myers Squibb Company, Wallingford, Connecticut 06492, USA
    J Med Chem 52:4173-91. 2009
    ..Compound 12p was efficacious in the defensive withdrawal test (an animal model of anxiety) in rats. The synthesis, structure-activity relationships and in vivo properties of compounds within the pyrazinone chemotype are described...
  13. doi request reprint Synthesis and SAR of hydroxyethylamine based phenylcarboxyamides as inhibitors of BACE
    Yong Jin Wu
    Neuroscience Discovery Chemistry, Bristol Myers Squibb Research and Development, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 19:2654-60. 2009
    ..A variety of P2 and P3 substituents has been explored, and these efforts have culminated in the identification of several 1,3,5-trisubstituted phenylcarboxyamides with potent BACE inhibitory activity...
  14. doi request reprint Conformationally restricted homotryptamines. Part 5: 3-(trans-2-aminomethylcyclopentyl)indoles as potent selective serotonin reuptake inhibitors
    Derek J Denhart
    Bristol Myers SquibbPharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492 7660, USA
    Bioorg Med Chem Lett 19:4031-3. 2009
    ..The most active analog was synthesized stereospecifically and the active enantiomer was shown to have high affinity binding to hSERT...
  15. doi request reprint Comparative biotransformation of pyrazinone-containing corticotropin-releasing factor receptor-1 antagonists: minimizing the reactive metabolite formation
    Xiaoliang Zhuo
    Departments of Biotransformation, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA
    Drug Metab Dispos 38:5-15. 2010
    ....
  16. doi request reprint Synthesis and structure-activity relationships of N3-pyridylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists
    Richard A Hartz
    Neuroscience Discovery Chemistry, Research and Development, Bristol Myers Squibb Company, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 20:1890-4. 2010
    ..Analogues containing a novel 6-(difluoromethoxy)-2,5-dimethylpyridin-3-amine group were among the most potent N(3)-pyridylpyrazinones synthesized. The synthesis and SAR of N(3)-pyridylpyrazinones is described herein...
  17. doi request reprint Design, synthesis and evaluation of constrained tetrahydroimidazopyrimidine derivatives as antagonists of corticotropin-releasing factor type 1 receptor (CRF1R)
    Vivekananda M Vrudhula
    Bristol Myers Squibb Research and Development, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 20:1905-9. 2010
    ..Initial lead compound 16 (K(i)=32 nM) demonstrated modest putative anxiolytic effects in the mouse canopy test. Further optimization using parallel synthesis provided compounds with K(i)'s <50 nM...
  18. doi request reprint Discovery of 6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethylamines, a novel class of corticotropin-releasing factor receptor type 1 (CRF1R) antagonists
    Dmitry Zuev
    Bristol Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 20:3669-74. 2010
    ..The optimization of binding affinity in the series by the parallel reaction approach is discussed herein...
  19. doi request reprint 5-arylamino-1,2,4-triazin-6(1H)-one CRF1 receptor antagonists
    William D Schmitz
    Neuroscience Discovery Chemistry, Bristol Myers Squibb Research and Development, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 20:3579-83. 2010
    ..Formation of CYP-mediated oxidative reactive metabolites previously observed in a related N(3)-phenylpyrazinone structure was minimized by incorporation of the additional ring nitrogen found in the triazinones...
  20. doi request reprint Conformationally restricted homotryptamines. Part 7: 3-cis-(3-aminocyclopentyl)indoles as potent selective serotonin reuptake inhibitors
    H Dalton King
    Bristol Myers Squibb, 5 Research Parkway, Wallingford, Connecticut 06492, United States
    J Med Chem 53:7564-72. 2010
    ..By contrast, 9a did not produce a significant increase in extracellular serotonin in rat frontal cortex at 3 mg/kg po due to relatively low brain and plasma levels...
  21. doi request reprint P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors in mice
    Jere E Meredith
    Research and Development, Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT, USA
    J Pharmacol Exp Ther 326:502-13. 2008
    ....
  22. ncbi request reprint Amino(methyl) pyrrolidines as novel scaffolds for factor Xa inhibitors
    Yan Shi
    Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 17:5952-8. 2007
    ....
  23. ncbi request reprint Conformationally restricted homotryptamines. Part 4: Heterocyclic and naphthyl analogs of a potent selective serotonin reuptake inhibitor
    H Dalton King
    Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492 7660, USA
    Bioorg Med Chem Lett 17:5647-51. 2007
    ..The most potent isosteres were CN-substituted naphthalenes. These results demonstrate that isosteric aromatic cores which lack an H-bond donor site may be substituted for the indole nucleus without substantial loss in hSERT binding...
  24. ncbi request reprint Discovery of N-isoxazolyl biphenylsulfonamides as potent dual angiotensin II and endothelin A receptor antagonists
    Natesan Murugesan
    Discovery Chemistry and Metabolic and Cardiovascular Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 5400, USA
    J Med Chem 45:3829-35. 2002
    ..Compound 15 represents a new approach to treating hypertension...
  25. ncbi request reprint Substituted pyrazolopyridopyridazines as orally bioavailable potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction
    Guixue Yu
    Discovery Chemistry, Drug Metabolism and Pharmacokinetics, Drug Safety, and Metabolic and Cardiovascular Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 5400, USA
    J Med Chem 46:457-60. 2003
    ..The superior isozyme selectivity of 6 is expected to exert less adverse effects in humans when used for erectile dysfunction treatment...
  26. ncbi request reprint beta-alanine dipeptides as MC4R agonists
    Réjean Ruel
    Bristol Myers Squibb Pharmaceutical Research Institute, 100 boul de l Industrie, Candiac, Quebec, Canada J5R 1J1
    Bioorg Med Chem Lett 13:4341-4. 2003
    ..beta-Alanine derivative 2 (IC(50)=16 nM) and related compounds were found to be potent MC4R agonists...
  27. ncbi request reprint Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics
    Natesan Murugesan
    Discovery Chemistry and Metabolic and Cardiovascular Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 5400 USA
    J Med Chem 48:171-9. 2005
    ....
  28. ncbi request reprint Tryptamine and homotryptamine-based sulfonamides as potent and selective inhibitors of 15-lipoxygenase
    David S Weinstein
    Bristol Myers Squibb Pharmaceutical Research Institute, Bristol Myers Squibb, PO Box 4000, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 15:1435-40. 2005
    ..g., 37a-p) proved to be potent inhibitors of the isolated enzyme. Selected compounds also demonstrated desirable inhibition selectivities over isozymes 5- and P-12-LO...
  29. ncbi request reprint Homotryptamines as potent and selective serotonin reuptake inhibitors (SSRIs)
    William D Schmitz
    Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492 7660, USA
    Bioorg Med Chem Lett 15:1619-21. 2005
    ..Initial attempts at conformational restriction of the propylamine sidechain by incorporation of a quinuclidine bicyclic structure did not improve binding affinity at SERT...
  30. doi request reprint Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1
    Lawrence R Marcin
    Bristol Myers Squibb, Research and Development, 5 Research Parkway, Wallingford, CT 06492 7660, USA
    Bioorg Med Chem Lett 21:537-41. 2011
    ..The same analog exhibited a high efflux ratio in a bidirectional Caco-2 assay and was likely a substrate of the efflux transporter P-glycoprotein. X-ray crystal structures are reported for two indole HEAs in complex with BACE-1...
  31. ncbi request reprint Novel dual action AT1 and ETA receptor antagonists reduce blood pressure in experimental hypertension
    Mark C Kowala
    Department of Metabolic and Cardiovascular Drug Discovery 025 289, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
    J Pharmacol Exp Ther 309:275-84. 2004
    ..Therefore compounds C and D are novel agents for treating a broad spectrum of patients with essential hypertension and other cardiovascular diseases...
  32. ncbi request reprint Characterization of the in vitro atropisomeric interconversion rates of an endothelin A antagonist by enantioselective liquid chromatography
    Yueer Shi
    Bristol Myers Squibb Company, Pharmaceutical Research Institute, P O Box 4000, Princeton, NJ 08543 4000, USA
    J Chromatogr A 1078:67-73. 2005
    ..It was therefore demonstrated that atropisomeric interconversion studies for the compound studied required consideration of temperature, presence of plasma proteins, and drug concentration to account for the kinetic data...
  33. ncbi request reprint Discovery of 4'-[(imidazol-1-yl)methyl]biphenyl-2-sulfonamides as dual endothelin/angiotensin II receptor antagonists
    John E Tellew
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 13:1093-6. 2003
    ..Certain compounds in the present series are orally active in a rat model of angiotensin II-mediated hypertension...
  34. doi request reprint The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression
    Catherine R Burton
    Bristol Myers Squibb Research and Development, Wallingford, Connecticut 06492, USA
    J Biol Chem 283:22992-3003. 2008
    ..Hypothetical mechanisms for the Abeta rise, including the "incomplete processing" and endocytic models, are discussed...
  35. ncbi request reprint Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction
    Yingzhi Bi
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543 5400, USA
    Bioorg Med Chem Lett 14:1577-80. 2004
    ..Substitutents at the C3-position can incorporate a variety of different groups. The synthesis and primary structure-activity relationship of this new series of potent PDE5 inhibitors are described...
  36. ncbi request reprint Enantioselective synthesis of a highly potent selective serotonin reuptake inhibitor. An application of imidazolidinone catalysis to the alkylation of indoles with an alpha,beta-disubstituted alpha,beta-unsaturated aldehyde
    H Dalton King
    Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA
    Org Lett 7:3437-40. 2005
    ..A rationale is presented for the unexpected stereochemical result, as well as the novel reactivity of the alpha-branched substrate. [reaction: see text]..
  37. ncbi request reprint A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice
    Liya Kang
    Bristol Myers Squibb Pharmaceutical Research Institute, Pennington, NJ 08534, USA
    J Leukoc Biol 80:897-904. 2006
    ....
  38. ncbi request reprint Discovery of tyrosine-based potent and selective melanocortin-1 receptor small-molecule agonists with anti-inflammatory properties
    Timothy F Herpin
    Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 5400, Princeton, New Jersey 08543, USA
    J Med Chem 46:1123-6. 2003
    ..Compound 2 is the first highly potent and selective MC-1R small-molecule agonist reported. Compound 2 showed efficacy in an acute model of inflammation, which has demonstrated the role of MC-1R in modulation of inflammation...