title: Replacement of amide with bioisosteres led to a new series of potent adenosine A2A receptor antagonists.
abstract: We have previously reported a series of 2,4,6-trisubstituted pyrimidines as potent A2A receptor antagonists. The leading compounds often feature a potentially labile acetamide functional group which tends to hydrolyze under acidic conditions. Here we report the replacement of the acetamide functional group with bioisosteres. This effort led us to a new series of adenosine A2A receptor antagonists with improved potency and chemical stability.
authors: Jiangsu Key Laboratory of Translational Research and Experimental Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, P. R. China.
authors: Zhaohui
authors: Z
authors: Yang
authors: Jiangsu Key Laboratory of Translational Research and Experimental Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, P. R. China.
authors: Xuan
authors: X
authors: Li
authors: Jiangsu Key Laboratory of Translational Research and Experimental Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, P. R. China.
authors: Haikuo
authors: H
authors: Ma
authors: Jiangsu Key Laboratory of Translational Research and Experimental Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, P. R. China.
authors: Jiyue
authors: J
authors: Zheng
authors: Jiangsu Key Laboratory of Translational Research and Experimental Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, P. R. China.
authors: Xuechu
authors: X
authors: Zhen
authors: Jiangsu Key Laboratory of Translational Research and Experimental Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, P. R. China. Electronic address: xiaohuzhang@suda.edu.cn.
authors: Xiaohu
authors: X
authors: Zhang
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D058917:Adenosine A2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; C030686:acetamide
keywords: Adenosine receptor; Antagonist; Bioisostere; GPCR; Parkinson’s disease