Research Topics
| Siobhan MalanySummaryAffiliation: Chugai Pharma USA Country: USA Publications
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Detail Information
Publications
Analytical method for simultaneously measuring ex vivo drug receptor occupancy and dissociation rate: application to (R)-dimethindene occupancy of central histamine H1 receptorsSiobhan 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-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 2. Reduction of hERG activity, observed species selectivity, and structure-activity relationshipsDeborah 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... - Lead optimization of 4-acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A2A adenosine receptor antagonists for the treatment of Parkinson's diseaseXiaohu Zhang
Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, California 92130, USA
J Med Chem 51:7099-110. 2008.... - N-[6-amino-2-(heteroaryl)pyrimidin-4-yl]acetamides as A2A receptor antagonists with improved drug like properties and in vivo efficacyMarion 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... - 2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A(2A) antagonists with improved solubility and metabolic stabilityManisha 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... - Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonistsXiaohu 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... - 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 insomniaSatheesh 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... - 2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 1. Structure-activity relationships and optimization of heterocyclic substituentsDeborah H Slee
Department of Medicinal Chemistry, Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA
J Med Chem 51:1719-29. 2008.... - Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomniaWilna 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... - Influence of pKa on the biotransformation of indene H1-antihistamines by CYP2D6Charles 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... - Novel benzothiophene H1-antihistamines for the treatment of insomniaWilna 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... - Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomniaTimothy 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... - 2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A(2A) antagonists with reduced hERG liabilityManisha 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... - Selectivity profiling of novel indene H(1)-antihistamines for the treatment of insomniaBin 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... - The discovery and structure-activity relationships of 2-(piperidin-3-yl)-1H-benzimidazoles as selective, CNS penetrating H1-antihistamines for insomniaKarine 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... - Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomniaWilna 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... 
A novel cell-based assay for G-protein-coupled receptor-mediated cyclic adenosine monophosphate response element binding protein phosphorylationJulie V Selkirk
Department of Neuroscience, Neurocrine Biosciences Inc, San Diego, CA 92130, USA
J Biomol Screen 11:351-8. 2006....- Identification of novel, water-soluble, 2-amino-N-pyrimidin-4-yl acetamides as A2A receptor antagonists with in vivo efficacyDeborah 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... - Single amino acid residue determinants of non-peptide antagonist binding to the corticotropin-releasing factor1 (CRF1) receptorSam 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....