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

Archive for October 12th, 2006


Posted by kinasepro on October 12, 2006

Guten Tag Schering AG,

Nice antibacterial you’ve got there posing as a kinase inhibitor. It seems like there’s a handful of these thiazolidinone PLK1 patent applications floating around. This offering from Schering isn’t their first of the series (WO2003093249, WO2005042505, WO2006082107) but it will be the first to get Kinasepro’s meat cleaver approach to figuring out how it’s binding. All Schering’s applications embody matter around the thiazolidinone core, with some subtle some not-so-subtle changes to the pendant functional groups.

To the best of KP’s knowledge there are no published Xrays of the kinase domain. It was looking like MIT had a patented one until you read the fine print and find its only another of the ‘polo-box-domain’ Pshaw Acadamics. Schering has a patent application on using a homology model for making these suckers, so don’t you even think about using this at home kids.

So what I’m getting at is that this is really just a guess, if there’s something public that your aware of that could help my understanding please feel free to chime in.

Posted in Plk1, Schering AG | 2 Comments »


Posted by kinasepro on October 12, 2006

Hello Kirin Brewing Company,

**Hmm… Maybe brand-name is all part of the business model…
Kinasepro’s Japanese is worse then his German, but your name popping onto his radar obviated a little digging. So it seems that for a while Kirin has been putting the Tarceva/Iressa-like quinazoline core onto kinase active lipophillic groups. But what made Kinasepro’s left eyebrow raise noticeably was when he came upone a Kirin patent application exemplifying the first use of a kinase active acyl urea.  High Five Man! Diaryl-ureas put the ‘ol KP to sleep you know, but show me something new like an acyl urea, and woohoo! The kinasepro is walking on air. (EGF; WO2003000660)

Esai took the idea and ran with some Nexavar-Like followons (VEGF: WO2005082854 [a 600 pager]), and BMS was quick to pick up the structural fragment first in a series of PP1 analogs (US2005239820), and to their credit then applied the modification in a similar fasion to Esai to find c-Met activity with some pyridine compounds that too remind one of Nexavar (US2005245530). As per an earlier post, it appears that BMS has found some creative isosteres, namely that pyridones fit (US20060211695) , and they’ve even patented a process route to get to the amides (US20050288289) suggesting a developement candidate can’t be far behind.

Basically what Kinasepro sees here is Kirin stealing back what BMS stole first. Hey man, fair is fair..

Domo Arigato

Posted in c-Met | 3 Comments »


Posted by kinasepro on October 12, 2006

& WO2006104915

Hi Glaxo,

You appear to still be committed to your p38 program for which KP is mighty pleased. Think you could you hurry it up a little though please?

The Evolution of a dream:

Looking at the body of matter here it seem like the difluorophenyl is key. Where does it fit? Well, there’s 3 somewhat relevant kinase PDB’s with this functional group: 1H00, 1PYE, 2CHL interestingly all three have the difluorophenyl ring located in the same space but I’ll be darned if I can get a good overlay with the Glaxo compound.

They’ve published a couple of structures from P38: Org. Lett. 2005, 4753 but they look as though they’re from an alternate series which hasn’t seen nearly as much love.

Posted in GSK, p38 | 2 Comments »

Did you know?

Posted by kinasepro on October 12, 2006

There’s apparantly a journal called: Expert Opinion on Therapeutic Patents.
And has been since 1990… Yah, me neither. I guess I can close my new blog then, Eh?

Posted in Uncategorized | Leave a Comment »