名称:
Synthesis and SAR studies of analogues of 4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-N-thiazol-2-yl-benzamide (Lu AA41063) as adenosine A2A receptor ligands with improved aqueous solubility
摘要:
An adenosine A(2A) receptor antagonist may be useful for the treatment of Parkinson's disease. Synthesis and structure-activity studies starting from 4-(3,3-dimethylbutyrylamino)-3,5-difluoro-N-thiazol-2-yl-benzamide (Lu AA41063, 4) led to a novel series of human (h) A(2A) receptor antagonists with improved aqueous solubility. Compound 22 was identified as a key representative from the series, displaying sub-micromolar hA(2A) receptor affinity and excellent aqueous solubility. Compound 22 also displayed good in vitro pharmacokinetic properties and is considered a good starting point for further lead optimisation toward hA(2A) receptor antagonists with improved druggability properties. (C) 2015 Elsevier Ltd. All rights reserved.