Author/Authors :
Roger J. Gillespie، نويسنده , , Samantha J. Bamford، نويسنده , , Alex Clay، نويسنده , , Suneel Gaur، نويسنده , , Tim Haymes، نويسنده , , Philip S. Jackson، نويسنده , , Allan M. Jordan، نويسنده , , Burkhard Klenke، نويسنده , , Stefania Leonardi، نويسنده , , Jeanette Liu، نويسنده , , Howard L. Mansell، نويسنده , , Sean Ng، نويسنده , , Mona Saadi، نويسنده , , Heather Simmonite، نويسنده , , Gemma C. Stratton، نويسنده , , Richard S. Todd، نويسنده , , Douglas S. Williamson، نويسنده , , Ian A. Yule، نويسنده ,
Abstract :
Antagonists of the human A2A receptor have been reported to have potential therapeutic benefit in the alleviation of the symptoms associated with neurodegenerative movement disorders such as Parkinson’s disease. As part of our efforts to discover potent and selective antagonists of this receptor, we herein describe the detailed optimization and structure–activity relationships of a series of pyrimidine-4-carboxamides. These optimized derivatives display desirable physiochemical and pharmacokinetic profiles, which have led to promising oral activity in clinically relevant models of Parkinson’s disease.
