arrow6 Comments
  1. Chemjobber
    Jul 13 - 3:07 pm

    I vote for metabolic stability — is it a coincidence that they’re all on phenolic alcohols (other than it’s a handy place to alkylate?)

  2. See Arr Oh
    Jul 13 - 3:26 pm

    @Chemjobber – While I’m tempted to say yes, there’s a few examples (doxylamine, deramciclane, clofenciclan) where the “tail” is connected to tertiary alcohols, albeit at benzylic positions…

  3. T
    Jul 13 - 8:51 pm

    Two epoxides? A Michael accepting enone?

    This molecule will nuke every nucleophile in your body.

    No way will the FDA ever let this molecule be administered chronically.

  4. See Arr Oh
    Jul 14 - 10:24 am

    @T – While it’s a valid point (and the molecule hasn’t been advanced to large-scale human trials yet), the idea springs from two known natural products, fumagillin and ovalicin. In France, fumagillin, at least, has been granted orphan drug status (Sanofi-Aventis) for the treatment of intestinal microsporidial infection.

  5. Curious Wavefunction
    Jul 14 - 3:44 pm

    I vote for improved solubility through the addition of a polar group; without the tail the molecule would be pretty lipophilic. They had used a similar strategy for improving solubility and cell permeability for some of the early HIV protease inhibitors.

  6. [...] of fumagillin analogs.  The two epoxide rings seem to be critical for MetAP2 inhibition, and the (N,N-dimethylamino) ethyl ether moiety seems to be a popular functional group that may improve potency and resist metabolic oxidation. [...]

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