KinasePro

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

SR-3451

Posted by kinasepro on March 4, 2009

O=C(NC1=CC(OC)=C(OC)C(OC)=C1)C2=CC=CC(N3N=CC4=C3C=CC(NC5=CC=CC=C5F)=C4)=C2.O=C(NC6=CC(OC)=C(OC)C(OC)=C6)C7=CC=CC(N8N=CC(NC(NC9=CC=CC=C9)=O)=C8)=C7

Not your grandmothers diaryl urea -> aryl-amino-indazole, 3FI3, & 3FI2 snake around a methionine GK

an’ fer anyone worried about the minor artifacts in the original I suspect it’ll be updated soon:

3fi21

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4 Responses to “SR-3451”

  1. fromsgc said

    Something is wrong with 3FI2. Pyrazol ring is not planar. Connection to urea is tetrahedral. Urea itself is twisted around. All of this in 2.3A structure…

  2. kinasepro said

    Yeh, kind of amateurish. When I see this kind of thing I ponder the resolution which seems ok in this case. Then I think perhaps it reflects that that we are seeing is some sort of time average of multiple conformations. That too seems unusual seeing as how the pyrazole ring forms a hydrogen bond, and I wouldn’t expect it that.

  3. milkshake said

    These X-ray structures were obtained by soaking ligands into pre-made crystals. With a fairly good resolution – but it was done by a postdoc and he did not even have his own X-ray machine (but he was very productive).

    These compounds have an interesting profile because they have high isoform selectivity, JNK3 vs JNK1. Please note that the aryl-NH group opens up a new binding pocket not present in the original binding site.

  4. ~f(x) said

    Sometimes even docs with their own machines can make such mistakes. Read Gerhard Kleywegt’s fine rant.

    Limitations and lessons in the use of X-ray structural information in drug design
    Andrew M. Davis1, , , Stephen A. St-Gallay1 and Gerard J. Kleywegt
    doi:10.1016/j.drudis.2008.06.006

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