Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1-yl) pyridin-3-yl) …

…, CA Fleener, KA Rouleau, M Obermeier…

Index: Watterson, Scott H.; Chen, Ping; Zhao, Yufen; Gu, Henry H.; Dhar, T. G. Murali; Xiao, Zili; Ballentine, Shelley K.; Shen, Zhongqi; Fleener, Catherine A.; Rouleau, Katherine A.; Obermeier, Mary; Yang, Zheng; McIntyre, Kim W.; Shuster, David J.; Witmer, Mark; Dambach, Donna; Chao, Sam; Mathur, Arvind; Chen, Bang-Chi; Barrish, Joel C.; Robl, Jeffrey A.; Townsend, Robert; Iwanowicz, Edwin J. Journal of Medicinal Chemistry, 2007 , vol. 50, # 15 p. 3730 - 3742

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Citation Number: 44

Abstract

Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical ...