A A Hancock

Summary

Affiliation: Abbott Laboratories
Country: USA

Publications

  1. doi request reprint Pharmacological properties and procognitive effects of ABT-288, a potent and selective histamine H3 receptor antagonist
    Timothy A Esbenshade
    Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 343:233-45. 2012
  2. ncbi request reprint Two novel and selective nonimidazole histamine H3 receptor antagonists A-304121 and A-317920: I. In vitro pharmacological effects
    Timothy A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 305:887-96. 2003
  3. ncbi request reprint Differential CNS expression and functional activity of multiple human H(3) receptor isoforms
    T A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, 60064, USA
    Inflamm Res 55:S38-9. 2006
  4. ncbi request reprint Pharmacological classification of histamine H3 receptor agents across species is attributable to transmembrane 3 sequence differences
    T A Esbenshade
    Department R4MN, AP9A 3, Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Inflamm Res 56:S45-6. 2007
  5. ncbi request reprint Differences in pharmacological properties of histamine H(3) receptor agonists and antagonists revealed at two human H (3) receptor isoforms
    T A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL, 60064 6125, USA
    Inflamm Res 55:S45-6. 2006
  6. ncbi request reprint The challenge of drug discovery of a GPCR target: analysis of preclinical pharmacology of histamine H3 antagonists/inverse agonists
    A A Hancock
    Abbott Laboratories, Global Pharmaceutical Research and Development, Department R4MN, Abbott Park, IL 60064 6125, USA
    Biochem Pharmacol 71:1103-13. 2006
  7. ncbi request reprint Use of novel, non-imidazole inverse agonist radioligands to define histamine H3 receptor pharmacology
    T A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Inflamm Res 54:S46-7. 2005
  8. ncbi request reprint Differential activation of dual signaling responses by human H1 and H2 histamine receptors
    Timothy A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Recept Signal Transduct Res 23:17-31. 2003
  9. ncbi request reprint Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H3 receptor antagonist with drug-like properties
    Timothy A Esbenshade
    Neuroscience Research, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 313:165-75. 2005
  10. pmc The histamine H3 receptor: an attractive target for the treatment of cognitive disorders
    T A Esbenshade
    Division of Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 154:1166-81. 2008

Detail Information

Publications82

  1. doi request reprint Pharmacological properties and procognitive effects of ABT-288, a potent and selective histamine H3 receptor antagonist
    Timothy A Esbenshade
    Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 343:233-45. 2012
    ..Thus, ABT-288 is a selective H(3)R antagonist with broad procognitive efficacy in rodents and excellent drug-like properties that support its advancement to the clinical area...
  2. ncbi request reprint Two novel and selective nonimidazole histamine H3 receptor antagonists A-304121 and A-317920: I. In vitro pharmacological effects
    Timothy A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 305:887-96. 2003
    ..7 and 7.0) than are the imidazole antagonists. These novel and selective piperazine amides represent useful leads for the development of H3R antagonist therapeutic agents...
  3. ncbi request reprint Differential CNS expression and functional activity of multiple human H(3) receptor isoforms
    T A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, 60064, USA
    Inflamm Res 55:S38-9. 2006
  4. ncbi request reprint Pharmacological classification of histamine H3 receptor agents across species is attributable to transmembrane 3 sequence differences
    T A Esbenshade
    Department R4MN, AP9A 3, Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Inflamm Res 56:S45-6. 2007
  5. ncbi request reprint Differences in pharmacological properties of histamine H(3) receptor agonists and antagonists revealed at two human H (3) receptor isoforms
    T A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL, 60064 6125, USA
    Inflamm Res 55:S45-6. 2006
  6. ncbi request reprint The challenge of drug discovery of a GPCR target: analysis of preclinical pharmacology of histamine H3 antagonists/inverse agonists
    A A Hancock
    Abbott Laboratories, Global Pharmaceutical Research and Development, Department R4MN, Abbott Park, IL 60064 6125, USA
    Biochem Pharmacol 71:1103-13. 2006
    ..This commentary provides an overview of these complexities as applied to the H(3) receptor and the challenges these intricacies create for drug discovery...
  7. ncbi request reprint Use of novel, non-imidazole inverse agonist radioligands to define histamine H3 receptor pharmacology
    T A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Inflamm Res 54:S46-7. 2005
  8. ncbi request reprint Differential activation of dual signaling responses by human H1 and H2 histamine receptors
    Timothy A Esbenshade
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Recept Signal Transduct Res 23:17-31. 2003
    ..86 and 4.82, respectively). These studies demonstrate a markedly different potency for activation of multiple signaling pathways by H1- and H2-HRs that may contribute to the selectivity of histamine responses in vivo...
  9. ncbi request reprint Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H3 receptor antagonist with drug-like properties
    Timothy A Esbenshade
    Neuroscience Research, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Pharmacol Exp Ther 313:165-75. 2005
    ..Thus, ABT-239 is a selective, nonimidazole H3 receptor antagonist/inverse agonist with similar high potency in both human and rat and favorable drug-like properties...
  10. pmc The histamine H3 receptor: an attractive target for the treatment of cognitive disorders
    T A Esbenshade
    Division of Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 154:1166-81. 2008
    ..The discovery of effective H3 antagonists as therapeutic agents for the novel treatment of cognitive disorders will only be accomplished through continued research efforts that further our insights into the functions of the H3 receptor...
  11. ncbi request reprint Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist
    Timothy A Esbenshade
    Abbott Laboratories, Global Pharmaceutical Research Division, Department of Neuroscience Research, Abbott Park, IL 60064, USA
    Biochem Pharmacol 68:933-45. 2004
    ..Thus, A-349821 is a novel, selective non-imidazole H3 antagonist/inverse agonist with balanced high potency across species and favorable cognition enhancing effects in rats...
  12. ncbi request reprint Use of an inverse agonist radioligand [3H]A-317920 reveals distinct pharmacological profiles of the rat histamine H3 receptor
    B Bei Yao
    Neuroscience Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Neuropharmacology 50:468-78. 2006
    ..These findings show that [(3)H]A-317920 is a potent rat H(3) receptor antagonist radioligand and has utility for studying H(3) receptor pharmacology...
  13. ncbi request reprint In vitro pharmacological properties of two novel non-imidazole H3 receptor (H3R) antagonists
    B B Yao
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A, R4MN, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    Inflamm Res 52:S45-6. 2003
  14. ncbi request reprint Antiobesity evaluation of histamine H3 receptor (H3R) antagonist analogs of A-331440 with improved safety and efficacy
    A A Hancock
    Department R4MN, AP9A 3, Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Inflamm Res 54:S27-9. 2005
  15. ncbi request reprint A new family of histamine H3 receptor antagonists based on a natural product: discovery, SAR, and properties of the series
    M Cowart
    Abbott Laboratories, GPRD Neuroscience Research, R4MN, AP9a 216, Abbott Park, IL 60064 6123, USA
    Inflamm Res 56:S47-8. 2007
  16. ncbi request reprint D-alanine piperazine-amides: novel non-imidazole antagonists of the histamine H3 receptor
    R Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP 9A, R4MN, Abbott Park, IL 60064 6123, USA
    Inflamm Res 52:S47-8. 2003
  17. ncbi request reprint Selective H3 receptor (H3R) blockade: broad efficacy in cognition and schizophrenia
    G B Fox
    Neuroscience Research, Abbott Laboratories, AP9A, Global Pharmaceutical Research and Development, Abbott Park, Illinois 60064, USA
    Inflamm Res 54:S23-4. 2005
  18. ncbi request reprint Species-related pharmacological heterogeneity of histamine H(3) receptors
    L Ireland-Denny
    Neuroscience Research, Department R4MN, Abbott Laboratories, Building AP9A, 100 Abbott Park Road, Abbott Park, IL 60064-6125, USA
    Eur J Pharmacol 433:141-50. 2001
    ..Therefore, genetic heterogeneity, rather than peripheral and central histamine H(3) receptor diversity, is responsible for the pharmacological differences observed...
  19. ncbi request reprint Structure-activity relationships of A-331440: a new histamine-3 antagonist with anti-obesity properties
    R Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064 6123, USA
    Inflamm Res 53:S79-80. 2004
  20. ncbi request reprint Achievement of behavioral efficacy and improved potency in new heterocyclic analogs of benzofuran H3 antagonists
    M Cowart
    Department R4MN, AP9a 216, Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
    Inflamm Res 54:S25-6. 2005
  21. ncbi request reprint Identification of novel H3 receptor (H3R) antagonists with cognition enhancing properties in rats
    G B Fox
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A, R4N5, 100 Abbott Park Rd, Abbott Park, Illinois 60064 6115, USA
    Inflamm Res 52:S31-2. 2003
  22. ncbi request reprint Two novel and potent 3-[(o-methoxyphenyl)piperazinylethyl]-5-phenylthien
    W A Carroll
    Abbott Laboratories, Neurological and Urological Diseases Research, Abbott Park, IL 60064 6101, USA
    Bioorg Med Chem Lett 11:1119-21. 2001
    ..The synthesis and in vitro characterization of A-119637 and A-123189, two novel, selective and potent alpha1D antagonists, are described...
  23. ncbi request reprint Distinctions and contradistinctions between antiobesity histamine H(3) receptor (H (3)R) antagonists compared to cognition-enhancing H (3) receptor antagonists
    A A Hancock
    Department R4MN, AP9A 3, Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL, 60064 6125, USA
    Inflamm Res 55:S42-4. 2006
  24. ncbi request reprint Molecular and pharmacological characterization of the monkey histamine H(3) receptor
    B B Yao
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Inflamm Res 53:S75-6. 2004
  25. ncbi request reprint Fluorescent benzofuran histamine H(3) receptor antagonists with sub-nanomolar potency
    M Cowart
    GPRD Neuroscience Research, R4MN, AP9a 216, Abbott Laboratories, Abbott Park, IL, 60064 6123, USA
    Inflamm Res 55:S47-8. 2006
  26. ncbi request reprint Aminoalkoxybiphenylnitriles as histamine-3 receptor ligands
    Ramin Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 12:3077-9. 2002
    ..Biaryl nitrile amines were prepared and found to have high affinity and selectivity for human and rat histamine H(3) receptors...
  27. ncbi request reprint Molecular modeling and pharmacological analysis of species-related histamine H(3) receptor heterogeneity
    B B Yao
    Neuroscience Research, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Neuropharmacology 44:773-86. 2003
    ..A model has been developed to elucidate the ligand receptor interactions for H(3)Rs, and pharmacological aspects of this model are described...
  28. ncbi request reprint Structure-activity studies for a novel series of bicyclic substituted hexahydrobenz[e]isoindole alpha1A adrenoceptor antagonists as potential agents for the symptomatic treatment of benign prostatic hyperplasia
    M D Meyer
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 44:1971-85. 2001
    ..Compound 48 showed the highest degree of selectivity in the radioligand binding assays (56-fold), in the in vitro functional tests (80-fold), and for in vivo prostate selectivity (960-fold)...
  29. ncbi request reprint Cognition enhancing effects of novel H(3) receptor (H(3)R) antagonists in several animal models
    G B Fox
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Inflamm Res 53:S49-50. 2004
  30. ncbi request reprint Cardiovascular activity of A-74283, a 5-hydroxytryptamine 1A agent, in the spontaneously hypertensive rat
    J Y Lee
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL, USA
    Pharmacology 56:17-29. 1998
    ..These data demonstrate that A-74283 exerts a potent hypotensive effect in SHR via systemic vasodilation originating from a central 5HT1A receptor mechanism. A-74283 may be useful for studying 5HT1A receptors and cardiovascular function...
  31. ncbi request reprint The medicinal chemistry of novel H(3) antagonists
    M Cowart
    Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    Inflamm Res 53:S69-70. 2004
  32. ncbi request reprint Histaminergic ligands attenuate barrel rotation in rats following unilateral labyrinthectomy
    J B Pan
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL, USA
    Methods Find Exp Clin Pharmacol 20:771-7. 1998
    ..These results indicate that this model may be a potential tool for testing novel drugs for antivertigo effects and provide better support to the role of the histaminergic system in the control of vestibular function...
  33. ncbi request reprint Synthesis and SAR of 5-amino- and 5-(aminomethyl)benzofuran histamine H3 receptor antagonists with improved potency
    Minghua Sun
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 48:6482-90. 2005
    ..The synthesis, SAR of the H3 binding affinities, in vitro assay for phospholipidosis, and pharmacokinetic properties of the new compounds are described...
  34. ncbi request reprint Histamine H(3) antagonists in models of obesity
    A A Hancock
    Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Inflamm Res 53:S47-8. 2004
  35. doi request reprint A robust and high-capacity [(35)S]GTPgammaS binding assay for determining antagonist and inverse agonist pharmacological parameters of histamine H(3) receptor ligands
    Thomas R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6125, USA
    Assay Drug Dev Technol 6:339-49. 2008
    ..These robust and reliable [(35)S]GTPgammaS binding assays have become one of the important tools in our pharmacological analysis and development of novel histamine H(3) receptor antagonists/inverse agonists...
  36. ncbi request reprint In vitro SAR of pyrrolidine-containing histamine H3 receptor antagonists: trends across multiple chemical series
    Diana L Nersesian
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:355-9. 2008
    ..The libraries were constructed with a variety of low molecular weight pyrrolidines, selected from (R)-2-methylpyrrolidine, (S)-2-methylpyrrolidine, and pyrrolidine...
  37. ncbi request reprint Synthesis, potency, and in vivo profiles of quinoline containing histamine H3 receptor inverse agonists
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 50:5439-48. 2007
    ..Further studies on the pharmaceutic properties of this series of quinolines discovered a potential problem with photochemical instability, an issue which contributed to the discontinuation of this series from further development...
  38. ncbi request reprint Preclinical pharmacology of fiduxosin, a novel alpha(1)-adrenoceptor antagonist with uroselective properties
    Arthur A Hancock
    Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064 6125, USA
    J Pharmacol Exp Ther 300:478-86. 2002
    ....
  39. ncbi request reprint Novel heterocyclic-substituted benzofuran histamine H3 receptor antagonists: in vitro properties, drug-likeness, and behavioral activity
    Marlon Cowart
    GPRD_AP9a 216, Department of Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Biochem Pharmacol 73:1243-55. 2007
    ..v. administration (t(1/2) in rat of 2.9h, 1.7h in dog, 1.8h in monkey), suggesting poor human pharmacokinetics, the data overall indicated that A-688057 has an excellent profile for use as a pharmacological tool compound...
  40. ncbi request reprint 4-[6-(2-Aminoethyl)naphthalen-2-yl]benzonitriles are potent histamine H3 receptor antagonists with high CNS penetration
    Lawrence A Black
    Neuroscience Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 17:1443-6. 2007
    ..The SAR of the tertiary amine moiety is similar to that reported for the benzofuran series, with analogs bearing a 2-methylpyrrolidine substituent possessing the greatest rat and human H3 receptor binding affinities...
  41. ncbi request reprint Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety
    Ana M Basso
    Neuroscience, Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Eur J Pharmacol 540:115-20. 2006
    ..The lack of efficacy with four structurally different MCH-1 receptor antagonists does not support a role for therapeutic treatment of depression/anxiety via this mechanism of action...
  42. ncbi request reprint Evidence for tolerance following repeated dosing in rats with ciproxifan, but not with A-304121
    Jia Bao Pan
    Neuroscience Research, Abbott Laboratories, 100 Abbott Road, Abbott Park, IL 60064 6125, USA
    Life Sci 79:1366-79. 2006
    ..The implications for potential long-term treatment with H(3) receptor antagonists in CNS disorders such as ADHD are discussed...
  43. doi request reprint The alkaloid conessine and analogues as potent histamine H3 receptor antagonists
    Chen Zhao
    Department of Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 51:5423-30. 2008
    ..One optimized analogue (13c) was examined in detail and was found to be efficacious in animal behavioral model of cognition...
  44. doi request reprint Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6100, USA
    J Med Chem 51:6571-80. 2008
    ....
  45. doi request reprint Antinociceptive effects of histamine H3 receptor antagonist in the preclinical models of pain in rats and the involvement of central noradrenergic systems
    Gin C Hsieh
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Brain Res 1354:74-84. 2010
    ..Our data also provide support that selective H(3) antagonists may represent a class of agents for the treatment of pain disorders...
  46. doi request reprint In vitro studies on a class of quinoline containing histamine H3 antagonists
    Huaqing Liu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 20:3295-300. 2010
    ..These analogs were synthesized via the Friedlander quinoline synthesis between an aminoaldehyde intermediate and a methyl ketone allowing for a wide diversity of substituents at the 2-position of the quinoline ring...
  47. doi request reprint Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: effects of substitution about the rigidifying ring
    John R Koenig
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6100, USA
    Bioorg Med Chem Lett 20:1900-4. 2010
    ..In addition, representative compounds are able to completely block itch responses when dosed ip in a mouse model of H(4)-agonist induced scratching, thus demonstrating their activities as H(4)R antagonists...
  48. doi request reprint H4 receptor antagonism exhibits anti-nociceptive effects in inflammatory and neuropathic pain models in rats
    Gin C Hsieh
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    Pharmacol Biochem Behav 95:41-50. 2010
    ..Our results demonstrate that selective blockade of H(4) receptors in vivo produces significant anti-nociception in animal models of inflammatory and neuropathic pain...
  49. doi request reprint Design of a new histamine H3 receptor antagonist chemotype: (3aR,6aR)-5-alkyl-1-aryl-octahydropyrrolo[3,4-b]pyrroles, synthesis, and structure-activity relationships
    Chen Zhao
    Department of Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 52:4640-9. 2009
    ..54 nM, rat H3 K(i) of 4.57 nM, and excellent pharmacokinetics (PK) profile in rats (oral bioavailability of 39% and t(1/2) of 2.4 h)...
  50. doi request reprint Cloning and characterization of the monkey histamine H3 receptor isoforms
    Marina I Strakhova
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, R 4MN, AP9A, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    Eur J Pharmacol 601:8-15. 2008
    ....
  51. doi request reprint Localization of histamine H4 receptors in the central nervous system of human and rat
    Marina I Strakhova
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Department R4MN, Abbott Park, Illinois 60064, USA
    Brain Res 1250:41-8. 2009
    ..Our observations provide evidence of the H(4) presence in both human and rodent CNS and offer some insight into possible role of H(4) in itch and pain...
  52. doi request reprint cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia
    Huaqing Liu
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6100, USA
    J Med Chem 51:7094-8. 2008
    ..Most interesting was the high potency and efficacy of this compound in blocking pain responses, where it showed an ED(50) of 42 mumol/kg (ip) in a rat post-carrageenan thermal hyperalgesia model of inflammatory pain...
  53. ncbi request reprint Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 2: binding preference for D-amino acids motifs
    Ramin Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 12:2035-7. 2002
    ..Structure-activity relationship studies on novel non-imidazole, D-amino acid containing ligands of histamine 3 receptors are presented. A-304121 is a D-alanine piperazine amide with high affinity at the rat H(3) receptor...
  54. doi request reprint Rotationally constrained 2,4-diamino-5,6-disubstituted pyrimidines: a new class of histamine H4 receptor antagonists with improved druglikeness and in vivo efficacy in pain and inflammation models
    Marlon D Cowart
    Department of Neuroscience Research, Abbott Laboratories, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 51:6547-57. 2008
    ..6 and 1.6 h, oral bioavailability of 37% and 90%) with anti-inflammatory activity (ED 50 = 37 micromol/kg, mouse) and efficacy in pain models (thermal hyperalgesia, ED 50 = 72 micromol/kg, rat)...
  55. pmc Detection of multiple H3 receptor affinity states utilizing [3H]A-349821, a novel, selective, non-imidazole histamine H3 receptor inverse agonist radioligand
    David G Witte
    Neuroscience Research, Dept R4MN, Global Pharmaceutical Research Division, Abbott Laboratories, Bldg AP9A 2, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Br J Pharmacol 148:657-70. 2006
    ..3H]A-349821 competition studies showed significant differences in the proportions and potencies of high- and low-affinity sites across species, providing new information about the fundamental pharmacological nature of H3 receptors...
  56. ncbi request reprint Effects of histamine H(3) receptor ligands GT-2331 and ciproxifan in a repeated acquisition avoidance response in the spontaneously hypertensive rat pup
    Gerard B Fox
    CNS Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A D4N5, Abbott Park, IL 60064, USA
    Behav Brain Res 131:151-61. 2002
    ..c.) blocked the pro-cognitive effects of ciproxifan, suggesting an H(3) receptor site of action for this compound. This model is useful for evaluating the cognition/attention-enhancing potential of H(3) receptor antagonists...
  57. ncbi request reprint Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 1
    Ramin Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 12:2031-4. 2002
    ..A high throughput screening lead, A-923, was further elaborated in a systematic manner to clarify a pharmacophore for this class of aryloxyalkyl piperazine based compounds...
  58. ncbi request reprint Cloning and pharmacological characterization of the monkey histamine H3 receptor
    Betty Bei Yao
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Eur J Pharmacol 482:49-60. 2003
    ....
  59. ncbi request reprint 4-(2-[2-(2(R)-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl)benzonitrile and related 2-aminoethylbenzofuran H3 receptor antagonists potently enhance cognition and attention
    Marlon Cowart
    Department of Neuroscience Research, Abbott Laboratories, Abbott Park, Illinois 60064 6123, USA
    J Med Chem 48:38-55. 2005
    ..The potency and selectivity of this compound and of analogues from this class support the potential of H(3) receptor antagonists for the treatment of cognitive dysfunction...
  60. ncbi request reprint An efficient multigram synthesis of the potent histamine H3 antagonist GT-2331 and the reassessment of the absolute configuration
    Huaqing Liu
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6123, USA
    J Org Chem 69:192-4. 2004
    ..However, we found that the dextrorotatory, more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole has the (1S,2S) absolute configuration. We suggest a reconsideration of the absolute configuration of GT-2331...
  61. ncbi request reprint Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: II. Neurophysiological characterization and broad preclinical efficacy in cognition and schizophrenia of a potent and selective histamine H3 re
    Gerard B Fox
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, AP9A, R4N5, Abbott Park, IL 60064 6115, USA
    J Pharmacol Exp Ther 313:176-90. 2005
    ..0 mg/kg), but not striatum. In summary, broad efficacy was observed with ABT-239 across animal models such that potential clinical efficacy may extend beyond disorders such as ADHD to include Alzheimer's disease and schizophrenia...
  62. ncbi request reprint In vitro optimization of structure activity relationships of analogues of A-331440 combining radioligand receptor binding assays and micronucleus assays of potential antiobesity histamine H3 receptor antagonists
    Arthur A Hancock
    Department of Exploratory Neurobiology, Global Pharmaceuticals Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Basic Clin Pharmacol Toxicol 95:144-52. 2004
    ..Preliminary findings with one of these examples, A-417022, in a mouse model of obesity are presented...
  63. ncbi request reprint Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 3: 5-Substituted 3-phenyl-1,2,4-oxadiazoles as potent antagonists
    Gregory A Gfesser
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 14:673-6. 2004
    ..Compound 14bb is a potent antagonist of both the rat cortical and human clone receptors, and is demonstrated to act functionally as an antagonist in an in vivo mouse dipsogenia model...
  64. ncbi request reprint Synthesis and structure-activity studies on N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide, an imidazole-containing alpha(1A)-adrenoceptor agonist
    Robert J Altenbach
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
    J Med Chem 47:3220-35. 2004
    ..However, the data also support a prominent role of the alpha(1A)-AR subtype in the control of MAP...
  65. ncbi request reprint D-amino acid homopiperazine amides: discovery of A-320436, a potent and selective non-imidazole histamine H(3)-receptor antagonist
    Michael P Curtis
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Arch Pharm (Weinheim) 337:219-29. 2004
    ..This compound was shown to demonstrate in vitro and in vivo functional antagonism and is non-neurotoxic at doses (i.p.) up to 163 mg/kg in a general observation test...
  66. ncbi request reprint A new class of potent non-imidazole H(3) antagonists: 2-aminoethylbenzofurans
    Marlon Cowart
    Department of Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 14:689-93. 2004
    ..The SAR of the basic amine moiety was compared in three different series of analogues. The greatest potency was found in analogues bearing a 2-methylpyrrolidine, a 2,5-dimethylpyrrolidine, or a 2,6-dimethylpiperidine...
  67. ncbi request reprint Antiobesity effects of A-331440, a novel non-imidazole histamine H3 receptor antagonist
    Arthur A Hancock
    Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Eur J Pharmacol 487:183-97. 2004
    ..The two higher doses reduced body fat and the highest dose also normalized an insulin tolerance test. These data show that the histamine H(3) receptor antagonist, A-331440, has potential as an antiobesity agent...
  68. ncbi request reprint Structure-activity relationships of arylbenzofuran H3 receptor antagonists
    Gregory A Gfesser
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 15:2559-63. 2005
    ..An SAR study of histamine H3 receptor antagonists based on substituted (R)-2-methyl-1-[2-(5-phenyl-benzofuran-2-yl)-ethyl]-pyrrolidines is presented...
  69. ncbi request reprint Genetic and pharmacological aspects of histamine H3 receptor heterogeneity
    Arthur A Hancock
    Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6125, USA
    Life Sci 73:3043-72. 2003
    ..The promise of newly available tools to further explore H3 receptor function may provide the insight to bring the promised clinical potential of H3 receptor ligands to realization...
  70. ncbi request reprint A new class of histamine H(3)-receptor antagonists: synthesis and structure-activity relationships of 7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolines
    Sean C Turner
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, 60064, Abbott Park, IL, USA
    Bioorg Med Chem Lett 13:2131-5. 2003
    ..Modifications of the amino substituents, optimization of chain length and the effect of conformational restraints are described. Several compounds with high affinity and selectivity for the H(3) receptor were discovered...
  71. ncbi request reprint Histamine H3 receptor antagonists: preclinical promise for treating obesity and cognitive disorders
    Timothy A Esbenshade
    Division of Neuroscience Research, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Mol Interv 6:77-88, 59. 2006
    ..Herein, we describe the biological and chemical implications for developing H3 receptor antagonists and their therapeutic potential as disclosed through animal models of cognition, sleep, and obesity...
  72. ncbi request reprint Differential in vivo effects of H3 receptor ligands in a new mouse dipsogenia model
    Gerard B Fox
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A, R4N5, Abbott Park, IL 60064 6115, USA
    Pharmacol Biochem Behav 72:741-50. 2002
    ..This new dipsogenia model provides the first in vivo behavioral evidence for possible pharmacological differences between three putative H(3) receptor inverse agonists, GT-2331 and proxyfan...
  73. ncbi request reprint Synthesis and SAR of aminoalkoxy-biaryl-4-carboxamides: novel and selective histamine H3 receptor antagonists
    Ramin Faghih
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park 60064 6123, USA
    Bioorg Med Chem Lett 13:1325-8. 2003
    ..Most compounds were highly potent and selective for human and rat H(3) receptors and selected examples such as A-349821 showed functional antagonism of H(3) receptors in vitro and in a mouse dipsogenia model...
  74. ncbi request reprint Two novel and selective nonimidazole H3 receptor antagonists A-304121 and A-317920: II. In vivo behavioral and neurophysiological characterization
    Gerard B Fox
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, AP9A, R4N5, 100 Abbott Park Road, Abbott Park, IL 60064 6115, USA
    J Pharmacol Exp Ther 305:897-908. 2003
    ..A-304121 and A-317920 represent a series of novel, H3R-selective piperazine amides that enhance cognition in vivo, which could offer advantages over existing H3R antagonists or cognition-enhancing agents...
  75. ncbi request reprint G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations
    Kathleen M Krueger
    Neurosciences Research, Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, IL 60064 6125, USA
    J Pharmacol Exp Ther 314:271-81. 2005
    ....
  76. ncbi request reprint Synthesis and evaluation of potent pyrrolidine H(3) antagonists
    Anil Vasudevan
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60031, USA
    Bioorg Med Chem Lett 12:3055-8. 2002
    ..A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable, to afford several compounds with high affinity and selectivity for the H(3) receptor...
  77. ncbi request reprint Histamine in cardiac sympathetic ganglia: a novel neurotransmitter?
    Ryan M Fryer
    Department of Integrative Pharmacology, Abbott Laboratories, Abott Park, IL 60064 6119, USA
    Mol Interv 6:14-9, 2. 2006
    ..Although histamine does elicit many effects in the heart, does it stand up to rigorous scrutiny and fulfill certain criteria that are used to define neurotransmitters?..
  78. pmc Use of the H3 receptor antagonist radioligand [3H]-A-349821 to reveal in vivo receptor occupancy of cognition enhancing H3 receptor antagonists
    T R Miller
    Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 157:139-49. 2009
    ..This model was established as an alternative to ex vivo binding methods, for relating antagonist H3 receptor occupancy to blood levels and efficacy in preclinical models...
  79. pmc In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties
    M I Strakhova
    Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
    Br J Pharmacol 157:44-54. 2009
    ..In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H4 receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine)...
  80. doi request reprint Minimization of potential hERG liability in histamine H3 receptor antagonists
    L A Black
    Abbott Laboratories, GPRD Neuroscience Research, R4MN, AP9a 216, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
    Inflamm Res 57:S45-6. 2008
  81. ncbi request reprint Comparison of alpha 1-adrenoceptor agonists in canine urethral pressure profilometry and abdominal leak point pressure models
    M E Brune
    Neurological and Urological Disease Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6118, USA
    J Urol 166:1555-9. 2001
    ..This leak point pressure test appears be useful for the preclinical evaluation of compounds used to treat stress urinary incontinence...
  82. ncbi request reprint Cloning of the human alpha 1d-adrenergic receptor and inducible expression of three human subtypes in SK-N-MC cells
    T A Esbenshade
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Mol Pharmacol 47:977-85. 1995
    ....