TY - JOUR
T1 - Mycophenolic acid analogs with a modified metabolic profile
AU - Chen, Liqiang
AU - Wilson, Daniel J.
AU - Labello, Nicholas P.
AU - Jayaram, Hiremagalur N.
AU - Pankiewicz, Krzysztof W.
PY - 2008/10/15
Y1 - 2008/10/15
N2 - Mycophenolic acid (MPA), a clinically used immunosuppressant, is extensively metabolized into an inactive C7-glucuronide and removed from circulation. To circumvent the metabolic liability imposed by the C7-hydroxyl group, we have designed a series of hybrid MPA analogs based on the pharmacophores present in MPA and new generations of inosine monophosphate dehydrogenase (IMPDH) inhibitors. The synthesis of MPA analogs has been accomplished by an allylic substitution of a common lactone. Biological evaluations of these analogs and a preliminary structure-activity relationship (SAR) are presented.
AB - Mycophenolic acid (MPA), a clinically used immunosuppressant, is extensively metabolized into an inactive C7-glucuronide and removed from circulation. To circumvent the metabolic liability imposed by the C7-hydroxyl group, we have designed a series of hybrid MPA analogs based on the pharmacophores present in MPA and new generations of inosine monophosphate dehydrogenase (IMPDH) inhibitors. The synthesis of MPA analogs has been accomplished by an allylic substitution of a common lactone. Biological evaluations of these analogs and a preliminary structure-activity relationship (SAR) are presented.
KW - Allylic substitution
KW - Inosine monophosphate dehydrogenase
KW - Mycophenolic acid
UR - http://www.scopus.com/inward/record.url?scp=53249154201&partnerID=8YFLogxK
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U2 - 10.1016/j.bmc.2008.08.062
DO - 10.1016/j.bmc.2008.08.062
M3 - Article
C2 - 18809333
AN - SCOPUS:53249154201
SN - 0968-0896
VL - 16
SP - 9340
EP - 9345
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 20
ER -