Identification of ring-fused pyrazolo pyridin-2-ones as novel poly(ADP-ribose)polymerase-1 inhibitorsWilna J Moree
Deltagen Research Laboratories Former CombiChem, Inc, 4570 Executive Drive, Suite 400, San Diego, CA 92121, USA
Bioorg Med Chem Lett 18:5126-9. 2008
..Compounds displayed low nanomolar binding activity in the PARP-1 binding assay and submicromolar activity in a cell based chemosensitization assay...
- 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...
- The expanding role of H1 antihistamines: a patent survey of selective and dual activity compounds 2005-2010
Graham Beaton
Drug Discovery Consultant
Expert Opin Ther Pat 20:1197-218. 2010
..The H(1) receptor is a key element in the pathophysiology of allergic responses. H(1) antihistamine use is a key strategy for therapy in allergy...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
Small molecule antagonists of the CCR2b receptor. Part 2: Discovery process and initial structure-activity relationships of diamine derivativesWilna J Moree
Deltagen Research Laboratories, 4570 Executive Drive, Suite 400, San Diego, CA 92121, USA
Bioorg Med Chem Lett 14:5413-6. 2004
..Several alternative structural series have been discovered that display nanomolar activity in the CCR2b binding and CCR2b-mediated chemotaxis assays...
- Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series
Wilna J Moree
Deltagen Research Laboratories Former CombiChem, Inc, 4570 Executive Drive, San Diego, CA 92121, USA
Bioorg Med Chem Lett 18:1869-73. 2008
..2 nM; MCP-1-Induced Chemotaxis IC(50) 0.83 nM; Ca(2+) Flux IC(50) 7.5 nM]...
