Mycophenolic acid analogs with a modified metabolic profile.
Article Details
- CitationCopy to clipboard
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]
- 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