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Literature DB >> 12014950

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.

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.

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.

Entities: Chemical Disease Species

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Year: 2002 PMID： 12014950 DOI： 10.1021/jm0105777

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

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Cited

6 in total

Review 1. IMP dehydrogenase: structure, mechanism, and inhibition.

Authors: Lizbeth Hedstrom
Journal: Chem Rev Date: 2009-07 Impact factor: 60.622

2. The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity.

Authors: Fouzia Machrouhi; Nouara Ouhamou; Keith Laderoute; Joy Calaoagan; Marina Bukhtiyarova; Paula J Ehrlich; Anthony E Klon
Journal: Bioorg Med Chem Lett Date: 2010-09-19 Impact factor: 2.823

3. Bacillus anthracis inosine 5'-monophosphate dehydrogenase in action: the first bacterial series of structures of phosphate ion-, substrate-, and product-bound complexes.

Authors: Magdalena Makowska-Grzyska; Youngchang Kim; Ruiying Wu; Rosemarie Wilton; Deviprasad R Gollapalli; Ximi K Wang; Rongguang Zhang; Robert Jedrzejczak; Jamey C Mack; Natalia Maltseva; Rory Mulligan; T Andrew Binkowski; Piotr Gornicki; Misty L Kuhn; Wayne F Anderson; Lizbeth Hedstrom; Andrzej Joachimiak
Journal: Biochemistry Date: 2012-07-25 Impact factor: 3.162

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.

Review 1. IMP dehydrogenase: structure, mechanism, and inhibition.

2. The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity.

3. Bacillus anthracis inosine 5'-monophosphate dehydrogenase in action: the first bacterial series of structures of phosphate ion-, substrate-, and product-bound complexes.

4. Identification of novel Mt-Guab2 inhibitor series active against M. tuberculosis.

5. In silico design of human IMPDH inhibitors using pharmacophore mapping and molecular docking approaches.

Review 6. Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story.