|
|||||
|
|
2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A(2A) antagonists with improved solubility and metabolic stability |
|
| Authors: | 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 |
| Affiliation: | Department of Medicinal Chemistry, Neurocrine Biosciences, 12780 El Camino Real, San Diego, CA 92130, USA. mmoorjani@neurocrine.com |
| 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 A(1) and improved solubility of >4 mg/mL at pH 8.0. 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. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |