1. JNJ-40255293, a novel adenosine A2A/A1 antagonist with efficacy in preclinical models of Parkinson's disease.

    ACS Chemical Neuroscience 5(10):1005 (2014) PMID 25203719

    Adenosine A2A antagonists are believed to have therapeutic potential in the treatment of Parkinson's disease (PD). We have characterized the dual adenosine A2A/A1 receptor antagonist JNJ-40255293 (2-amino-8-[2-(4-morpholinyl)ethoxy]-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one). JNJ-40255293 was a h...
  2. Substituted thieno[2,3-d]pyrimidines as adenosine A2A receptor antagonists.

    Bioorganic & Medicinal Chemistry Letters 23(9):2688 (2013) PMID 23522563

    A novel series of benzyl substituted thieno[2,3-d]pyrimidines were identified as potent A2A receptor antagonists. Several five- and six-membered heterocyclic replacements for the optimized methylfuran were explored. Select compounds effectively reverse catalepsy in mice when dosed orally. Copyri...
  3. Design and characterization of optimized adenosine A₂A/A₁ receptor antagonists for the treatment of Parkinson's disease.

    Journal of medicinal and pharmaceutical chemistry 55(3):1402 (2012) PMID 22239465

    The design and characterization of two, dual adenosine A(2A)/A(1) receptor antagonists in several animal models of Parkinson's disease is described. Compound 1 was previously reported as a potential treatment for Parkinson's disease. Further characterization of 1 revealed that it was metabolized...
  4. Overcoming the genotoxicity of a pyrrolidine substituted arylindenopyrimidine as a potent dual adenosine A(2A)/A(1) antagonist by minimizing bioactivation to an iminium ion reactive intermediate.

    Chemical Research in Toxicology 24(7):1012 (2011) PMID 21667953

    2-Amino-4-phenyl-8-pyrrolidin-1-ylmethyl-indeno[1,2-d]pyrimidin-5-one (1) is a novel and potent selective dual A(2A)/A(1) adenosine receptor antagonist from the arylindenopyrimidine series that was determined to be genotoxic in both the Ames and Mouse Lymphoma L5178Y assays only following metabo...
  5. Death receptor 6 negatively regulates oligodendrocyte survival, maturation and myelination.

    Nature Medicine 17(7):816 (2011) PMID 21725297

    Survival and differentiation of oligodendrocytes are important for the myelination of central nervous system (CNS) axons during development and crucial for myelin repair in CNS demyelinating diseases such as multiple sclerosis. Here we show that death receptor 6 (DR6) is a negative regulator of ...
  6. In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease.

    Journal of medicinal and pharmaceutical chemistry 53(22):8104 (2010) PMID 20973483

    The in vivo characterization of a dual adenosine A(2A)/A(1) receptor antagonist in several animal models of Parkinson's disease is described. Discovery and scale-up syntheses of compound 1 are described in detail, highlighting optimization steps that increased the overall yield of 1 from 10.0% t...
  7. Optimization of arylindenopyrimidines as potent adenosine A2A/A1antagonists

    Bioorganic & Medicinal Chemistry Letters 20(9):2868 (2010) PMID 20338760

    Two reactive metabolites were identified in vivo for the dual A 2A/A 1 receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, e...
  8. Optimization of arylindenopyrimidines as potent adenosine A2A/A1antagonists

    Bioorganic & Medicinal Chemistry Letters 20(9):2868 (2010) PMID 20338760

    Two reactive metabolites were identified in vivo for the dual A 2A/A 1 receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, e...
  9. Methylene amine substituted arylindenopyrimidines as potent adenosine A2A/A1antagonists

    Bioorganic & Medicinal Chemistry Letters 20(9):2864 (2010) PMID 20347304

    A novel series of arylindenopyrimidines were identified as A 2A and A 1 receptor antagonists. The series was optimized for in vitro activity by substituting the 8- and 9-positions with methylene amine substituents. The compounds show excellent activity in mouse models of Parkins...
  10. Methylene amine substituted arylindenopyrimidines as potent adenosine A2A/A1antagonists

    Bioorganic & Medicinal Chemistry Letters 20(9):2864 (2010) PMID 20347304

    A novel series of arylindenopyrimidines were identified as A 2A and A 1 receptor antagonists. The series was optimized for in vitro activity by substituting the 8- and 9-positions with methylene amine substituents. The compounds show excellent activity in mouse models of Parkins...
  11. Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors.

    Bioorganic & Medicinal Chemistry Letters 16(12):3096 (2006) PMID 16632358

    A series of novel carboxylic acid-based alpha-sulfone MMP inhibitors have been synthesized and the in vitro enzyme SAR is discussed. A potential binding mode in the active site of the MMP-9 homology model was highlighted. These compounds are potent MMP-9 inhibitors and are selective over MMP-1.
  12. Synthesis and SAR of α-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors

    Bioorganic & Medicinal Chemistry Letters 16(12):3096 (2006)

    A series of novel carboxylic acid-based α-sulfone MMP inhibitors have been synthesized and the in vitro enzyme SAR and in vivo PK evaluation are discussed. These compounds are potent MMP-9 inhibitors and are selective over MMP-1.
  13. Inhibitory effects of pimozide on cloned and native voltage-gated potassium channels.

    Molecular Brain Research 115(1):29 (2003) PMID 12824052

    The primary goal of this study was to use the cloned neuronal Kv channels to test if pimozide (PMZD), an antipsychotic drug, modulates the activity of Kv channels. In CHO cells, PMZD blocked Kv2.1, a major neuronal delayed rectifier, in a manner that depends upon time and concentration. The esti...