Patrick R Verhoest

Summary

Affiliation: Pfizer Global Research and Development
Country: USA

Publications

  1. doi request reprint Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disor
    Patrick R Verhoest
    Neuroscience Medicinal Chemistry, Pfizer World Wide Research and Development, 700 Main Street, Cambridge, Massachusetts 02139, United States
    J Med Chem 55:9045-54. 2012
  2. doi request reprint Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia
    Patrick R Verhoest
    Neuroscience, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    J Med Chem 52:5188-96. 2009
  3. doi request reprint Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242)
    Patrick R Verhoest
    Neuroscience Medicinal Chemistry, Pfizer PharmaTherapeutics Research and Development, Groton, Connecticut, USA
    J Med Chem 54:5868-77. 2011
  4. doi request reprint Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors
    Michelle M Claffey
    Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States
    J Med Chem 55:9055-68. 2012
  5. doi request reprint Design and selection parameters to accelerate the discovery of novel central nervous system positron emission tomography (PET) ligands and their application in the development of a novel phosphodiesterase 2A PET ligand
    Lei Zhang
    Neuroscience Medicinal Chemistry, Pfizer Inc, Cambridge, Massachusetts 02139, USA
    J Med Chem 56:4568-79. 2013
  6. pmc Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes
    Travis T Wager
    558 Eastern Point Road, Groton, CT, USA
    ACS Chem Neurosci 1:420-34. 2010
  7. doi request reprint Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo
    Robin J Kleiman
    SystaMedic Inc, 1084 Shennecossett Drive, Groton, CT 06340, USA
    J Pharmacol Exp Ther 341:396-409. 2012
  8. doi request reprint Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy
    Patrick R Verhoest
    Neuroscience Chemistry, Pfizer Global Research and Development, Groton, CT 06340, USA
    J Med Chem 52:7946-9. 2009
  9. pmc Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties
    Travis T Wager
    Neuroscience Medicinal Chemistry, Pfizer PharmaTherapeutics Research and Development, 558 Eastern Point Road, Groton, Connecticut, USA
    ACS Chem Neurosci 1:435-49. 2010
  10. doi request reprint PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency
    Amy B Dounay
    Pfizer Worldwide Research and Development, Neuroscience Medicinal Chemistry, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 23:1961-6. 2013

Collaborators

Detail Information

Publications12

  1. doi request reprint Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disor
    Patrick R Verhoest
    Neuroscience Medicinal Chemistry, Pfizer World Wide Research and Development, 700 Main Street, Cambridge, Massachusetts 02139, United States
    J Med Chem 55:9045-54. 2012
    ....
  2. doi request reprint Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia
    Patrick R Verhoest
    Neuroscience, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    J Med Chem 52:5188-96. 2009
    ..This PDE10A inhibitor is the first reported clinical entry for this mechanism in the treatment of schizophrenia...
  3. doi request reprint Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242)
    Patrick R Verhoest
    Neuroscience Medicinal Chemistry, Pfizer PharmaTherapeutics Research and Development, Groton, Connecticut, USA
    J Med Chem 54:5868-77. 2011
    ..This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers...
  4. doi request reprint Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors
    Michelle M Claffey
    Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States
    J Med Chem 55:9055-68. 2012
    ..Optimization afforded preclinical candidate 19 that demonstrated free brain/free plasma ≥ 1 in rat and reduced microsomal clearance along with the ability to increase cyclic guanosine monophosphosphate levels in rat CSF...
  5. doi request reprint Design and selection parameters to accelerate the discovery of novel central nervous system positron emission tomography (PET) ligands and their application in the development of a novel phosphodiesterase 2A PET ligand
    Lei Zhang
    Neuroscience Medicinal Chemistry, Pfizer Inc, Cambridge, Massachusetts 02139, USA
    J Med Chem 56:4568-79. 2013
    ....
  6. pmc Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes
    Travis T Wager
    558 Eastern Point Road, Groton, CT, USA
    ACS Chem Neurosci 1:420-34. 2010
    ....
  7. doi request reprint Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo
    Robin J Kleiman
    SystaMedic Inc, 1084 Shennecossett Drive, Groton, CT 06340, USA
    J Pharmacol Exp Ther 341:396-409. 2012
    ....
  8. doi request reprint Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy
    Patrick R Verhoest
    Neuroscience Chemistry, Pfizer Global Research and Development, Groton, CT 06340, USA
    J Med Chem 52:7946-9. 2009
    ..By use of chemical enablement and prospective design, a novel series of selective, brain penetrant PDE9A inhibitors have been identified that are capable of producing in vivo elevations of brain cGMP...
  9. pmc Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties
    Travis T Wager
    Neuroscience Medicinal Chemistry, Pfizer PharmaTherapeutics Research and Development, 558 Eastern Point Road, Groton, Connecticut, USA
    ACS Chem Neurosci 1:435-49. 2010
    ..Based on six physicochemical properties commonly used by medicinal chemists, the CNS MPO function may be used prospectively at the design stage to accelerate the identification of compounds with increased probability of success...
  10. doi request reprint PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency
    Amy B Dounay
    Pfizer Worldwide Research and Development, Neuroscience Medicinal Chemistry, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 23:1961-6. 2013
    ..53. The X-ray crystal structure of 20 with KAT II demonstrates key features that contribute to this remarkable potency and binding efficiency...
  11. doi request reprint Evaluating the Differences in Cycloalkyl Ether Metabolism Using the Design Parameter "Lipophilic Metabolism Efficiency" (LipMetE) and a Matched Molecular Pairs Analysis
    Antonia F Stepan
    Pfizer Worldwide Research and Development, 700 Main Street, Cambridge, Massachusetts 02139, United States
    J Med Chem 56:6985-90. 2013
    ..It is our hope that both the LipMetE design parameter and the results from our pairwise analysis will be useful tools for medicinal chemists. ..
  12. doi request reprint A general strategy for the synthesis of cyclic N-aryl hydroxamic acids via partial nitro group reduction
    Laura A McAllister
    Neuroscience Chemistry, Pfizer Worldwide R and D, Eastern Point Rd, Groton, Connecticut 06340, USA
    J Org Chem 76:3484-97. 2011
    ..In addition, a novel activated trifluoroethyl ester cyclization strategy has been developed as an alternate approach to the most sterically demanding systems in this series...