Discovery of AMP mimetics that exhibit high inhibitory potency and specificity for AMP deaminase

…, BC Bookser, PD van Poelje, MR Reddy…

Index: Erion, Mark D.; Kasibhatla, Srinivas Rao; Bookser, Brett C.; Van Poelje, Paul D.; Reddy, M. Rami; Gruber, Harry E.; Appleman, James R. Journal of the American Chemical Society, 1999 , vol. 121, # 2 p. 308 - 319

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Citation Number: 30

Abstract

The first potent, specific, and cell-penetrable AMP deaminase (AMPDA) inhibitors were discovered through an investigation of 3-substituted 3, 6, 7, 8-tetrahydroimidazo [4, 5-d][1, 3] diazepin-8-ol analogues. Inhibition constants for the most potent inhibitors were 105-fold lower than the KM for the substrate AMP. High affinity required the presence of both the 8- hydroxyl and the 3-substituent and is postulated to arise from a cooperative interaction ...