Robert W Carling

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi 3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1
    Robert W Carling
    Department of Medicinal Chemistry, The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Med Chem 47:1807-22. 2004
  2. ncbi An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties
    Mark S Chambers
    Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
    J Med Chem 47:5829-32. 2004
  3. ncbi 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activi
    Robert W Carling
    Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Med Chem 48:7089-92. 2005
  4. ncbi Discovery of imidazo[1,2-b][1,2,4]triazines as GABA(A) alpha2/3 subtype selective agonists for the treatment of anxiety
    Michael G N Russell
    J Med Chem 49:1235-8. 2006
  5. ncbi 2,3,7-Trisubstituted pyrazolo[1,5-d][1,2,4]triazines: functionally selective GABAA alpha3-subtype agonists
    Robert W Carling
    Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK
    Bioorg Med Chem Lett 16:3550-4. 2006
  6. ncbi Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazines and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site
    Leslie J Street
    Departments of Medicinal Chemistry, Biochemistry, and Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Med Chem 47:3642-57. 2004
  7. ncbi Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit
    Michael G N Russell
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, U K
    J Med Chem 48:1367-83. 2005
  8. ncbi N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists
    Jason M Elliott
    Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Bioorg Med Chem Lett 16:5748-51. 2006
  9. ncbi Imidazo[1,2-a]pyrazin-8-ones, imidazo[1,2-d][1,2,4]triazin-8-ones and imidazo[2,1-f][1,2,4]triazin-8-ones as alpha2/alpha3 subtype selective GABA A agonists for the treatment of anxiety
    Simon C Goodacre
    Neuroscience Research Centre, Merck, Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Bioorg Med Chem Lett 16:1582-5. 2006
  10. ncbi Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers
    Francine Sternfeld
    The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
    J Med Chem 47:2176-9. 2004

Collaborators

Detail Information

Publications12

  1. ncbi 3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1
    Robert W Carling
    Department of Medicinal Chemistry, The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Med Chem 47:1807-22. 2004
    ....
  2. ncbi An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties
    Mark S Chambers
    Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
    J Med Chem 47:5829-32. 2004
    ..It does not exhibit the convulsant, proconvulsant, or anxiogenic activity associated with nonselective GABA(A) inverse agonists...
  3. ncbi 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activi
    Robert W Carling
    Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Med Chem 48:7089-92. 2005
    ..Herein we describe a novel series of GABA(A) alpha2/alpha3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclinical animal assays...
  4. ncbi Discovery of imidazo[1,2-b][1,2,4]triazines as GABA(A) alpha2/3 subtype selective agonists for the treatment of anxiety
    Michael G N Russell
    J Med Chem 49:1235-8. 2006
    ..Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat and squirrel monkey behavioral models...
  5. ncbi 2,3,7-Trisubstituted pyrazolo[1,5-d][1,2,4]triazines: functionally selective GABAA alpha3-subtype agonists
    Robert W Carling
    Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK
    Bioorg Med Chem Lett 16:3550-4. 2006
    ....
  6. ncbi Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazines and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site
    Leslie J Street
    Departments of Medicinal Chemistry, Biochemistry, and Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    J Med Chem 47:3642-57. 2004
    ....
  7. ncbi Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit
    Michael G N Russell
    Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, U K
    J Med Chem 48:1367-83. 2005
    ..This was the first indication that selectivity in efficacy in the required direction could be achieved in this series...
  8. ncbi N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists
    Jason M Elliott
    Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Bioorg Med Chem Lett 16:5748-51. 2006
    ..In an ex vivo assay in gerbil, the lead compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30 mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK properties...
  9. ncbi Imidazo[1,2-a]pyrazin-8-ones, imidazo[1,2-d][1,2,4]triazin-8-ones and imidazo[2,1-f][1,2,4]triazin-8-ones as alpha2/alpha3 subtype selective GABA A agonists for the treatment of anxiety
    Simon C Goodacre
    Neuroscience Research Centre, Merck, Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Bioorg Med Chem Lett 16:1582-5. 2006
    ....
  10. ncbi Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers
    Francine Sternfeld
    The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
    J Med Chem 47:2176-9. 2004
    ..Compounds of this type may be useful in the symptomatic treatment of memory impairment associated with Alzheimer's disease and related dementias...
  11. ncbi 2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones: functionally selective benzodiazepine binding site ligands on the GABAA receptor
    Andrew Mitchinson
    Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow CM20 2QR, UK
    Bioorg Med Chem Lett 14:3441-4. 2004
    ..2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones are GABAA receptor benzodiazepine binding site ligands with functional selectivity for the alpha3 subtype over the alpha1 subtype. SAR studies to optimise this functional selectivity are described...
  12. ncbi N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II
    Jason M Elliott
    Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK
    Bioorg Med Chem Lett 16:5752-6. 2006
    ..The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ(90) 7 mg/kg po; plasma Occ(90) 0.4 microM) and has good selectivity and excellent PK properties...