학술논문
2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A2A antagonists with improved solubility and metabolic stability
Document Type
Article
Author
Moorjani, Manisha; Luo, Zhiyong; Lin, Emily; Vong, Binh G.; Chen, Yongsheng; Zhang, Xiaohu; Rueter, Jaimie K.; Gross, Raymond S.; Lanier, Marion C.; Tellew, John E.; Williams, John P.; Lechner, Sandra M.; Malany, Siobhan; Santos, Mark; Crespo, María I.; Díaz, José-Luis; Saunders, John; Slee, Deborah H.
Source
Subject
*PYRIMIDINES
*BIOTRANSFORMATION (Metabolism)
*DRUG receptors
*ADENOSINES
*PARKINSON'S disease
*MEDICAL research
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Language
ISSN
0960-894X
Abstract
Abstract: In this report, the strategy and outcome of expanding SAR exploration to improve solubility and metabolic stability are discussed. Compound 35 exhibited excellent potency, selectivity over A1 and improved solubility of >4mg/mL at pH 8.0. In addition, compound 35 had good metabolic stability with a scaled intrinsic clearance of 3mL/min/kg (HLM) and demonstrated efficacy in the haloperidol induced catalepsy model. [Copyright &y& Elsevier]