Synthesis and pharmacological characterization of N3-substituted willardiine derivatives: role of the substituent at the 5-position of the uracil ring in the development of …

…, D Bleakman, ML Mayer, GL Collingridge…

Index: Dolman, Nigel P.; More, Julia C. A.; Alt, Andrew; Knauss, Jody L.; Pentikaeinen, Olli T.; Glasser, Carla R.; Bleakman, David; Mayer, Mark L.; Collingridge, Graham L.; Jane, David E. Journal of Medicinal Chemistry, 2007 , vol. 50, # 7 p. 1558 - 1570

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Citation Number: 52

Abstract

Some N3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLUK5 revealed that there was allowed volume around the 4-and 5-positions of the thiophene ...