2. Academic Validation
  3. 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

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

  • J Med Chem. 2002 May 23;45(11):2127-30. doi: 10.1021/jm0105777.
T G Murali Dhar,  Zhongqi Shen,  Junqing Guo,  Chunjian Liu,  Scott H Watterson,  Henry H Gu,  William J Pitts,  Catherine A Fleener,  Katherine A Rouleau,  N Z Sherbina,  Kim W McIntyre,  David J Shuster,  Mark R Witmer,  Jeffrey A Tredup,  Bang-Chi Chen,  Rulin Zhao,  Mark S Bednarz,  Daniel L Cheney,  John F MacMaster,  Laura M Miller,  Karen K Berry,  Timothy W Harper,  Joel C Barrish,  Diane L Hollenbaugh,  Edwin J Iwanowicz
PMID: 12014950 DOI: 10.1021/jm0105777
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.

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