Discovery of N-[2-[2-[[3-Methoxy-4-(5-oxazolyl)phenyl]amino]-5-oxazolyl]phenyl]-N-methyl-4- morpholineacetamide as a Novel and Potent Inhibitor of Inosine Monophosphate Dehydrogenase with Excellent in Vivo Activity
Journal of Medicinal Chemistry2002Vol. 45(11), pp. 2127–2130
Citations Over TimeTop 21% of 2002 papers
T. G. Murali Dhar, Zhongqi Shen, Junqing Guo, Chunjian Liu, Scott H. Watterson, Henry H. Gu, William J. Pitts, Catherine Fleener, Katherine A. Rouleau, N.Z. Sherbina, Kim W. McIntyre, Mark R. Witmer, Jeffrey Tredup, Bang‐Chi Chen, Rui-Lin Zhao, Mark S. Bednarz, Daniel L. Cheney, John F. MacMaster, Laura M. Miller, Karen Berry, Timothy W. Harper, Joel C. Barrish, Diane Hollenbaugh, Edwin J. Iwanowicz
Abstract
Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme that is involved in the de novo synthesis of purine nucleotides. Novel 2-aminooxazoles were synthesized and tested for inhibition of IMPDH catalytic activity. Multiple analogues based on this chemotype were found to inhibit IMPDH with low nanomolar potency. One of the analogues (compound 23) showed excellent in vivo activity in the inhibition of antibody production in mice and in the adjuvant induced arthritis model in rats.
Related Papers
- → Analysis of ATP and Its Breakdown Products in Beef by Reversed‐Phase HPLC(1989)49 cited
- → Sensory Changes in Umami Taste of Inosine 5′‐Monophosphate Solution after Heating(1991)42 cited
- → INOSINE MONOPHOSPHATE (IMP) AND HYPOXANTHINE FORMATION IN THREE SPECIES OF SHRIMP HELD ON ICE(1971)14 cited
- → The amination of inosine monophosphate in skeletal muscle(1961)28 cited
- Towards personalized medicine: Utilizing biomarkers to track response of the inosine monophosphate dehydrogenase (IMPDH) inhibitor AVN944 patient samples from a Phase I clinical trial in AML and evaluation of a patient stratification signature.(2007)