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Identification of a New Series of Potent Adenosine A2A Receptor Antagonists Based on 4-Amino-5-carbonitrile Pyrimidine Template for the Treatment of Parkinson's Disease.
Yang, Zhaohui; Li, Linlang; Zheng, Jiyue; Ma, Haikuo; Tian, Sheng; Li, Jiajun; Zhang, Hongjian; Zhen, Xuechu; Zhang, Xiaohu.
Afiliación
  • Yang Z; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Li L; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Zheng J; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Ma H; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Tian S; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Li J; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Zhang H; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Zhen X; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
  • Zhang X; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University , Su Zhou, Jiangsu 215021, P. R. China.
ACS Chem Neurosci ; 7(11): 1575-1584, 2016 11 16.
Article en En | MEDLINE | ID: mdl-27569066
Adenosine receptor A2A antagonists have emerged as potential treatment for Parkinson's disease in the past decade. We have recently reported a series of adenosine receptor antagonists using heterocycles as bioisosteres for a potentially unstable acetamide. These compounds, while showing excellent potency and ligand efficiency, suffered from moderate cytochrome P450 inhibition and high clearance. Here we report a new series of adenosine receptor A2A antagonists based on a 4-amino-5-carbonitrile pyrimidine template. Compounds from this new template exhibit excellent potency and ligand efficiency with low cytochrome P450 inhibition. Although the clearance remains moderate to high, the leading compound, when dosed orally as low as 3 mg/kg, demonstrated excellent efficacy in the haloperidol induced catalepsy rat model for Parkinson's disease.
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Bases de datos: MEDLINE Asunto principal: Pirimidinas / Antagonistas del Receptor de Adenosina A2 / Antiparkinsonianos Tipo de estudio: Diagnostic_studies Idioma: En Revista: ACS Chem Neurosci Año: 2016 Tipo del documento: Article
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Bases de datos: MEDLINE Asunto principal: Pirimidinas / Antagonistas del Receptor de Adenosina A2 / Antiparkinsonianos Tipo de estudio: Diagnostic_studies Idioma: En Revista: ACS Chem Neurosci Año: 2016 Tipo del documento: Article