Design and synthesis of novel inhibitors of inosine monophosphate dehydrogenase

CARB 115

Guang-Yao Gao, guang004@umn.edu, Laurent Bonnac, bonna008@umn.edu, Liqiang Chen, Krzysztof Felczak, Martin Kullberg, Riccardo Petrelli, Eric M. Bennett, and Krzysztof W. Pankiewicz. Center for Drug Design, University of Minnesota, 516 Delaware St. SE, Minneapolis, MN 55455
Inosine Monophosphate Dehydrogenase (IMPDH) is a well known therapeutic target for new drug development against organ transplant rejection, viral infection and cancer due to its key role in de novo synthesis of purine nucleotides. Following our discovery of mycophenolic adenine dinucleotide (MAD) analogues such as C2-MAD, we designed and synthesized a series of C2-MAD analogues and evaluated their activities against IMPDH (type I and type II). We introduced different functional groups at the 2-position of adenine improving the potency and selectivity of new compounds against the type I and type II isoforms of the human enzyme. We also designed and synthesized compounds with new linkages between adenosine and mycophenolic moiety. Some of them showed more potent inhibition of IMPDH than the parent MAD analogues.

 

Carbohydrate Chemistry and Biochemistry
8:30 AM-11:50 AM, Thursday, August 23, 2007 BCEC -- 162B, Oral

Division of Carbohydrate Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007