Kinase Chemistry – Just a year and a half behind the times.


Posted by kinasepro on November 5, 2007

Arqule’s bRaf series recently published: WO/2007/123892


(Yah, I know the picture is ugly, and the ‘3D’ piperidine is the wrong stereo-isomer… use your imagination)

4 Responses to “Arqubraf”

  1. Funky heterocycle and I don’t even know what it’s called. Regardless of it’s name, it looks a bit electron-rich and oxidation of that sulfur could result in horrid reactive metabolite issue. On another note the sulfonamide conformation looks bad. But not as bad as a reactive metabolite! Thanks for serving up this abomination for me to vent my prejudices on. Wait, I just spotted the phenol…

  2. nucleardreams said

    phenol yet again

  3. braf.v660e said

    Though the phenol is not much better than the oxime pharmacophore in terms of potential tox liabilities, the docking model does suggest how to achieve some potentially selective interactions (Trp531).

  4. kinasepro said

    For the imidazole chemotype (SB-590885), the oxime has been described as a bioavailable replacement for the phenol actually… It appears that it was tried within this series, but bond angles being what they are, it didn’t make the tight squeeze.

    >> on second look, there is an active benzaldoxime in there: ex 395 is 18 nM

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