Mycophenolic acid analogs with a modified metabolic profile.

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Chen L, Wilson DJ, Labello NP, Jayaram HN, Pankiewicz KW

Mycophenolic acid analogs with a modified metabolic profile.

Bioorg Med Chem. 2008 Oct 15;16(20):9340-5. doi: 10.1016/j.bmc.2008.08.062. Epub 2008 Aug 29.

PubMed ID

18809333 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mycophenolic acid	Inosine-5'-monophosphate dehydrogenase 1	Ki (nM)	40	N/A	N/A	Details
Mycophenolic acid	Inosine-5'-monophosphate dehydrogenase 2	Ki (nM)	10	N/A	N/A	Details