arrow6 Comments
  1. Chemjobber
    Jan 05 - 2:14 pm

    Nice post, Carmen. Answered the question on my mind.

  2. Carmen Drahl
    Jan 05 - 2:54 pm

    I aim to inform, CJ. What’s cool to the chemist in me is that the spiroepoxide might still be around. That functional group is also part of the ketoepoxide in Onyx’s myeloma drug candidate carfilzomib-
    http://cenblog.org/the-haystack/2010/07/positive-results-for-onyxs-myeloma-drug-carfilzomib/

  3. Chemjobber
    Jan 05 - 3:35 pm

    You know, this is an interesting thing — what’s the clinical success rate of candidates with epoxides? In Pfizer language, it’s certainly (IIRC) a ‘structural alert.’ (Not that those are drug killers, just something to be careful of.)

    Seems to me that in Med Chem 101 type classes, it’s always mentioned as something you don’t want to do… (have a covalently reactive functionality present).

  4. Carmen Drahl
    Jan 05 - 3:52 pm

    This paper was a handy ‘covalent drugs’ resource in my grad school days:
    http://pubs.acs.org/doi/abs/10.1021/bi050247e

  5. David
    Jan 13 - 2:33 pm

    Carmen –

    That patent seems to point to CKD-732 (O-(4-Dimethylaminoethoxycinnamoyl)fumagillol, see http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=74585908&viewopt=PubChem ), which CKD has been testing as a (parenterally-available when combined with hydroxypropyl-beta-cyclodextrin) angiogenesis inhibitor (see http://dx.doi.org/10.1016/j.ijpharm.2003.11.034 ) as well as an anti-obesity drug (see http://jme.endocrinology-journals.org/cgi/content/full/38/4/455 ). The patent mentions a version where the oxirane ring is replaced by a methanol and an ethylhalogen (i.e. the version shown in the second pic above), but I have not seen any information about such versions being researched anywhere. Have you?

  6. Carmen Drahl
    Jan 13 - 6:38 pm

    Thanks for the additional information David. You are probably already aware of this but for the benefit of readers I will point out that Twitter user @Kristall36 pointed me to a 2000 BMCL paper from CKD on fumagillol analogs.
    http://dx.doi.org/10.1016/S0960-894X(99)00577-6

    I haven’t searched the literature for publications with structures like the one you describe (similar to the second pic). Sorry I can’t be more helpful!

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