Synthesis and Modeling Studies with Monocyclic Analogues of Mycophenolic Acid
1996; American Chemical Society; Volume: 39; Issue: 1 Linguagem: Inglês
10.1021/jm9501339
ISSN1520-4804
AutoresWayne K. Anderson, Terri L. Boehm, Gergely M. Makara, Rowan Swann,
Tópico(s)Renal Transplantation Outcomes and Treatments
ResumoTwo stepwise procedures, developed for the introduction of the (E)-4-methyl-4-hexenoic acid side chain of mycophenolic acid, were used in the synthesis of monocyclic mycophenolic acid analogues 2a−i. The derivatives with a methyl group or hydrogen at C-4 and lacking the lactone moiety were much less cytotoxic than mycophenolic acid. The monocyclic analogues with a C-4 chloro group did show some activity, albeit much less than mycophenolic acid. The observed differences in potency are rationalized by semiempirical calculations of intramolecular H-bonds.
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