Synthesis of the inosine 5′-monophosphate dehydrogenase (IMPDH) inhibitors

Figures & data

Figure 1. Currently used drugs that target IMPDH.

Figure 2. Structure of MPA 6.

Scheme 1. The synthesis of isobenzofuran analogs 8, 10 and 1137.

Figure 3. Isobenzofuran derivative 8a active in vitro toward both T-cells proliferation and IMPDH type inhibition37.

Scheme 2. The synthesis of analogs 16 and 1838.

Scheme 3. Synthesis of amino acid MPA derivative 17 and 18³⁹.

Figure 4. N-mycophenoyl-d-glutamic acid 18a39.

Scheme 4. NAD-based IMPDH inhibitors40.

Figure 5. Methylenebis(sulfonamide) analogs 21 of mycophenolic adenine methylenebis(phosphonate)s 2641.

Figure 6. MPA derivatives as dual IMPDH and HDAC inhibitors.

Scheme 5. Synthesis of N-(2,3,5-triazoyl)mycophenolic amide 3042.

Scheme 6. Synthesis of enantiomeric mycophenolic epoxyketones 33 and 34⁴².

Scheme 7. Synthesis of triazole-linked IMPDH inhibitor 37⁴³.

Scheme 8. Synthesis of conjugate of MPA and quinic acid derivative 4444.

Figure 7. Structure of 4′-hydroxymycophenolic acid 49 isolated from Penilillium fungus (sp. SOF07)45.

Scheme 9. Synthesis of dual HDAC and IMPDH inhibitor 51⁴⁸.

Scheme 10. Synthesis of merimepodib 54⁴⁹.

Scheme 11. Synthesis of 3-methoxy-4-(5-oxazolyl)aniline 52⁵².

Scheme 12. Synthesis of carbamate 55⁵³.

Scheme 13. Synthesis of BMS-337197 65^51,52.

Figure 8. Urea and diamide derivatives of cinnamic hydroxamic acid and N-(3-metoxy-4-(5-oxazolyl)phenyl]amine 69 and 7055.

Scheme 14. Synthesis of urea derivative 69a53.

Scheme 15. Structure and synthesis of quinolone derivatives 73⁵⁶.

Scheme 16. Synthesis of (5-oxazolyl)phenyl amines 7657.

Scheme 17. Synthesis of imidazole derivative of l-ascorbic acid 81⁵⁸.

Figure 9. Chemical structure of AS2643361 8258.

Scheme 18. Synthesis of BMS-566419 84⁶⁰.

Scheme 19. Synthesis of amine 8860.

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