Document Report Card

ID: ALA1136047

Journal: J Med Chem

Title: 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.

Authors: Dhar TG, Shen Z, Guo J, Liu C, Watterson SH, Gu HH, Pitts WJ, Fleener CA, Rouleau KA, Sherbina NZ, McIntyre KW, Shuster DJ, Witmer MR, Tredup JA, Chen BC, Zhao R, Bednarz MS, Cheney DL, MacMaster JF, Miller LM, Berry KK, Harper TW, Barrish JC, Hollenbaugh DL, Iwanowicz EJ.

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.

CiteXplore: 12014950

DOI: 10.1021/jm0105777