Research Topics
| J E MacorSummaryAffiliation: Bristol-Myers Squibb Country: USA Publications
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Detail Information
Publications
The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonistJ 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...- Stereoselective synthesis of new conformationally restricted analogues of a potent CGRP receptor antagonistDmitry 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... - 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 agonistJohn E Macor
CNS Discovery, AstraZeneca, 1800 Concord Pike, Wilmington, Delaware 19850 5437, USA
J Org Chem 69:6493-5. 2004.... - N-3-substituted imidazoquinazolinones: potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunctionD 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... - The discovery of novel, potent and selective PDE5 inhibitorsY 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... - Optimization of substituted N-3-benzylimidazoquinazolinone sulfonamides as potent and selective PDE5 inhibitorsD 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... 
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 peptidAndrew 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...- Catalytic asymmetric syntheses of tyrosine surrogatesXiaojun 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... - Catalytic asymmetric syntheses of alpha-amino and alpha-hydroxyl acid derivativesXiaojun 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.... - Carbamates as potent calcitonin gene-related peptide antagonists with improved solution stabilityAndrew 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)... - In vitro intrinsic clearance-based optimization of N3-phenylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonistsRichard 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... - Synthesis, structure-activity relationships, and in vivo evaluation of N3-phenylpyrazinones as novel corticotropin-releasing factor-1 (CRF1) receptor antagonistsRichard 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... - Synthesis and SAR of hydroxyethylamine based phenylcarboxyamides as inhibitors of BACEYong 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... - Conformationally restricted homotryptamines. Part 5: 3-(trans-2-aminomethylcyclopentyl)indoles as potent selective serotonin reuptake inhibitorsDerek 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... - Comparative biotransformation of pyrazinone-containing corticotropin-releasing factor receptor-1 antagonists: minimizing the reactive metabolite formationXiaoliang Zhuo
Departments of Biotransformation, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA
Drug Metab Dispos 38:5-15. 2010.... - Synthesis and structure-activity relationships of N3-pyridylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonistsRichard 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... - 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... - 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) antagonistsDmitry 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... - 5-arylamino-1,2,4-triazin-6(1H)-one CRF1 receptor antagonistsWilliam 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... - Conformationally restricted homotryptamines. Part 7: 3-cis-(3-aminocyclopentyl)indoles as potent selective serotonin reuptake inhibitorsH 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... - P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving enzyme 1 inhibitors in miceJere E Meredith
Research and Development, Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT, USA
J Pharmacol Exp Ther 326:502-13. 2008.... - Amino(methyl) pyrrolidines as novel scaffolds for factor Xa inhibitorsYan Shi
Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543 5400, USA
Bioorg Med Chem Lett 17:5952-8. 2007.... - Conformationally restricted homotryptamines. Part 4: Heterocyclic and naphthyl analogs of a potent selective serotonin reuptake inhibitorH 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... - Discovery of N-isoxazolyl biphenylsulfonamides as potent dual angiotensin II and endothelin A receptor antagonistsNatesan 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... - Substituted pyrazolopyridopyridazines as orally bioavailable potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunctionGuixue 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... - beta-alanine dipeptides as MC4R agonistsRéjean 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... - Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokineticsNatesan 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.... - Tryptamine and homotryptamine-based sulfonamides as potent and selective inhibitors of 15-lipoxygenaseDavid 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... - 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... - Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1Lawrence 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... - Novel dual action AT1 and ETA receptor antagonists reduce blood pressure in experimental hypertensionMark 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... - Characterization of the in vitro atropisomeric interconversion rates of an endothelin A antagonist by enantioselective liquid chromatographyYueer 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... - Discovery of 4'-[(imidazol-1-yl)methyl]biphenyl-2-sulfonamides as dual endothelin/angiotensin II receptor antagonistsJohn 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... - The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expressionCatherine 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... - Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunctionYingzhi 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... - 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 aldehydeH 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].. - A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in miceLiya Kang
Bristol-Myers Squibb Pharmaceutical Research Institute, Pennington, NJ 08534, USA
J Leukoc Biol 80:897-904. 2006.... - Discovery of tyrosine-based potent and selective melanocortin-1 receptor small-molecule agonists with anti-inflammatory propertiesTimothy 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...