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

Archive for October 14th, 2006


Posted by kinasepro on October 14, 2006

Hi BI, More aminopyrimidines?

More the merrier I say. No sulfur this series, but Kinasepro likes the ground you cover with these applications: EP1598343 (published 11/25/05)

The amine in example one is nice, and thanks for the experimental. (1>reductive amination 2>Pd/C, p54.) It looks as though you like it too, because it and some isosteres are heavily represented in the later generations. EP1630163 (published 3/1/06)

Not the standard solvent exposed yada-yada, though quite a bit different from the Amgen imidazalones. Second and a half generation: WO2006021378 (published 8/19/06) Looks as though you just realized the anilines were active, and rushed to cover them in this app. Hoho, otherwise this is the same as the previous, just reverse the [L]&C=O in the previous Markush.

Third Generation: WO2006021547, and WO2006021548 (Published 3/2/06) Kinasepro’s trick elbow tells him BI is closing in on something though he thinks you should have a talk with the guy who put your patents together. Is the the jumbled up A, R2, and R3 on page 43 enough to invalidate? Neh, but KP hopes your attorney lays off the 3-Heineken lunches. Nice set of amines anyhow. 

smiles: yah, KP is trying a new thing with smiles.  to see if they’er searchable.

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Posted by kinasepro on October 14, 2006

Hello there Amgen,

Welcome to Kinasepro, and thanks for playing the ‘hide the structure’ game.  (names only no structures given)  You’re  Markush makes it look like a Cyclacel rip, and KP wouldn’t be at all surprised if you started looking around near there, but I like how you’ve taken it a good bit further.  The region that I would consider ‘solvent exposed’ isn’t the typical yada-yada, but there are a few polar residues out there which it seems you’re likely picking up with those imidazolones.  The benzothiazole is a nice touch, and I’m also glad you were able to fit first and second generation compounds into the same application, less money to the layers is always good eh?

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Posted by kinasepro on October 14, 2006

Hi Cyclacel,

Yah we’re reaching back to last year, because it looks like you’ve patented an Xray (WO2005047526) but your webby still says all you’ve got is a model. The title of the app is: “Use of crystal structure of Plk1 kinase in screening for inhibitors…” So what gives? The app just has the coords of a model, but one would presume that was derived from a bona-fide xray. The models below shows the important Cys residue and calls it “C67”. Kinasepro likes how you dress up the application giving data on wartmannin (180 nM), staurosporine (800nM), purvalanol (5uM), LY2940002(9uM), and quercitin (65uM) Thanks for describing the docking of some various compounds. I notice you’ve done this kind of thing before with the CDK program. Good show. More interesting then your picture the ‘homology model’ is LANL’s stock model to the right. (could you xerox these things a few more times before sending them to the lawyer? Sheesh)

Even more better is the figure of adenosine, and thioadenosine, thanks for that.

I especially like your body of matter application (WO2005042525) and thoroughly guffawed at the title page xray complete with coordinates. That’s an xray of the compound, btw, not the complex… There really is no better way of saying:“THIS ISN’T HOW IT BINDS!” Thanks again for the heads up anyways, but lots of people including you have already shown that aminopyrimidines bind more like I’ve shown in D of the above figure. 1FPU is a good exception, but I don’t see that going on here. Of course as with some of the last posts, these are really just KP’s own educated guesses.


I’ll say this much anyhow: You’re thiazolones have KP wondering more and more about what’s going on with Schering’s stuff though.

Posted in Cyclacel, Plk1 | 1 Comment »


Posted by kinasepro on October 14, 2006

So Kinasepro’s homework for the evening was to catch up on some of the PLK1 application literature just to see what’s out there. Expecting to see some Schering rip-offs, I was surprised to find a robust cast of characters playing there parts on the Polo-like stage.

Structurally it appears that there’s a cystein residue on the inside of the p-loop which most of these applications appear to attempt to exploit in one fasion or another.

Don’t care about PLK1? Then you may want to check back in a bit…

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