Siobhan Malany

Summary

Affiliation: Chugai Pharma USA
Country: USA

Publications

  1. doi request reprint Analytical method for simultaneously measuring ex vivo drug receptor occupancy and dissociation rate: application to (R)-dimethindene occupancy of central histamine H1 receptors
    Siobhan Malany
    Division of Emerging New Technologies, Neurocrine Biosciences, San Diego, California, USA
    J Recept Signal Transduct Res 29:84-93. 2009
  2. doi request reprint 2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 2. Reduction of hERG activity, observed species selectivity, and structure-activity relationships
    Deborah H Slee
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
    J Med Chem 51:1730-9. 2008
  3. doi request reprint Lead optimization of 4-acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A2A adenosine receptor antagonists for the treatment of Parkinson's disease
    Xiaohu Zhang
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, California 92130, USA
    J Med Chem 51:7099-110. 2008
  4. doi request reprint N-[6-amino-2-(heteroaryl)pyrimidin-4-yl]acetamides as A2A receptor antagonists with improved drug like properties and in vivo efficacy
    Marion C Lanier
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, California 92130, USA
    J Med Chem 52:709-17. 2009
  5. doi request reprint 2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A(2A) antagonists with improved solubility and metabolic stability
    Manisha Moorjani
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 18:5402-5. 2008
  6. doi request reprint Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists
    Xiaohu Zhang
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 18:1778-83. 2008
  7. doi request reprint Lead optimization of 2-(piperidin-3-yl)-1H-benzimidazoles: identification of 2-morpholin- and 2-thiomorpholin-2-yl-1H-benzimidazoles as selective and CNS penetrating H₁-antihistamines for insomnia
    Satheesh Babu Ravula
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 22:421-6. 2012
  8. doi request reprint 2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 1. Structure-activity relationships and optimization of heterocyclic substituents
    Deborah H Slee
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
    J Med Chem 51:1719-29. 2008
  9. doi request reprint Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia
    Wilna J Moree
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 20:5874-8. 2010
  10. doi request reprint Influence of pKa on the biotransformation of indene H1-antihistamines by CYP2D6
    Charles Huang
    Neurocrine Biosciences, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 21:947-51. 2011

Collaborators

Detail Information

Publications19

  1. doi request reprint Analytical method for simultaneously measuring ex vivo drug receptor occupancy and dissociation rate: application to (R)-dimethindene occupancy of central histamine H1 receptors
    Siobhan Malany
    Division of Emerging New Technologies, Neurocrine Biosciences, San Diego, California, USA
    J Recept Signal Transduct Res 29:84-93. 2009
    ..Data described by the method may be analyzed with commercially available software. Suggested fitting procedures are given in the appendix...
  2. doi request reprint 2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 2. Reduction of hERG activity, observed species selectivity, and structure-activity relationships
    Deborah H Slee
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
    J Med Chem 51:1730-9. 2008
    ..In addition, the observed structure-activity relationships against both the human and the rat A 2A receptor are reported...
  3. doi request reprint Lead optimization of 4-acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A2A adenosine receptor antagonists for the treatment of Parkinson's disease
    Xiaohu Zhang
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, California 92130, USA
    J Med Chem 51:7099-110. 2008
    ....
  4. doi request reprint N-[6-amino-2-(heteroaryl)pyrimidin-4-yl]acetamides as A2A receptor antagonists with improved drug like properties and in vivo efficacy
    Marion C Lanier
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, California 92130, USA
    J Med Chem 52:709-17. 2009
    ..This approach significantly enhanced aqueous solubility and lowered the log P of the system to provide molecules without significant hERG or CYP liabilities and robust in vivo efficacy...
  5. doi request reprint 2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A(2A) antagonists with improved solubility and metabolic stability
    Manisha Moorjani
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 18:5402-5. 2008
    ..0. In addition, compound 35 had good metabolic stability with a scaled intrinsic clearance of 3 mL/min/kg (HLM) and demonstrated efficacy in the haloperidol induced catalepsy model...
  6. doi request reprint Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists
    Xiaohu Zhang
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 18:1778-83. 2008
    ..SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease...
  7. doi request reprint Lead optimization of 2-(piperidin-3-yl)-1H-benzimidazoles: identification of 2-morpholin- and 2-thiomorpholin-2-yl-1H-benzimidazoles as selective and CNS penetrating H₁-antihistamines for insomnia
    Satheesh Babu Ravula
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 22:421-6. 2012
    ..Compounds 9a and 9b in the morpholine series and 10g in the thiomorpholine series demonstrated improved selectivity and CNS profiles compared to lead compound 2 and these are potential candidates for evaluation as sedative hypnotics...
  8. doi request reprint 2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 1. Structure-activity relationships and optimization of heterocyclic substituents
    Deborah H Slee
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
    J Med Chem 51:1719-29. 2008
    ....
  9. doi request reprint Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia
    Wilna J Moree
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 20:5874-8. 2010
    ..One of these compounds, 10a, showed equivalent efficacy in a rat EEG/EMG model to a previously identified clinical candidate and a potentially superior pharmacokinetic profile as determined from a human microdose study...
  10. doi request reprint Influence of pKa on the biotransformation of indene H1-antihistamines by CYP2D6
    Charles Huang
    Neurocrine Biosciences, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 21:947-51. 2011
    ..Several compounds, including 8l, 8o, and 12f were identified with promising primary in vitro profiles and reduced biotransformation via CYP2D6...
  11. doi request reprint Novel benzothiophene H1-antihistamines for the treatment of insomnia
    Wilna J Moree
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 20:2316-20. 2010
    ..Compound 28b demonstrated lower predicted clearance in preclinical studies, and may represent a more suitable backup compound...
  12. doi request reprint Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia
    Timothy Coon
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 19:4380-4. 2009
    ..Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro profile...
  13. doi request reprint 2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A(2A) antagonists with reduced hERG liability
    Manisha Moorjani
    Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 18:1269-73. 2008
    ..The strategy and outcome of expanding SAR exploration to attenuate hERG and improve selectivity over A(1) are discussed. Compound 33 exhibited excellent potency, selectivity over A(1), and reduced hERG liability...
  14. doi request reprint Selectivity profiling of novel indene H(1)-antihistamines for the treatment of insomnia
    Bin Feng Li
    Neurocrine Biosciences, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 20:2629-33. 2010
    ..These compounds were candidates for further ADME profiling and in vivo evaluation...
  15. doi request reprint The discovery and structure-activity relationships of 2-(piperidin-3-yl)-1H-benzimidazoles as selective, CNS penetrating H1-antihistamines for insomnia
    Karine Lavrador-Erb
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA
    Bioorg Med Chem Lett 20:2916-9. 2010
    ..One example, 9q, retained a suitable selectivity profile with CNS exposure equivalent to known centrally active H(1)-antihistamines...
  16. doi request reprint Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia
    Wilna J Moree
    Neurocrine Biosciences, 12780 El Camino Real, San Diego, California 92130, USA
    J Med Chem 52:5307-10. 2009
    ..On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition...
  17. doi request reprint Identification of novel, water-soluble, 2-amino-N-pyrimidin-4-yl acetamides as A2A receptor antagonists with in vivo efficacy
    Deborah H Slee
    Department of Medicinal Chemistry, Pharmacology and Lead Discovery, Neuroscience, Chemical Development and Preclinical Development, Neurocrine Biosciences, San Diego, CA 92130, USA
    J Med Chem 51:400-6. 2008
    ..In addition, this series of compounds has demonstrated good bioavailability and in vivo efficacy in a rodent model of Parkinson's disease, despite having reduced potency for the rat A2A receptor versus the human A2A receptor...
  18. ncbi request reprint A novel cell-based assay for G-protein-coupled receptor-mediated cyclic adenosine monophosphate response element binding protein phosphorylation
    Julie V Selkirk
    Department of Neuroscience, Neurocrine Biosciences Inc, San Diego, CA 92130, USA
    J Biomol Screen 11:351-8. 2006
    ....
  19. ncbi request reprint Single amino acid residue determinants of non-peptide antagonist binding to the corticotropin-releasing factor1 (CRF1) receptor
    Sam R J Hoare
    Department of Discovery Biology, Neurocrine Biosciences Inc, 12790 El Camino Real, San Diego, CA 92130, USA
    Biochem Pharmacol 72:244-55. 2006
    ....