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

Archive for October 29th, 2006


Posted by kinasepro on October 29, 2006

To Kinasepro, the real personality behind Sorafenib, is the part about how they optimized against RAF only to find out later that it was the VEGFR2 and PDGFR-b activity that was driving the efficacy. Hmm, somehow they don’t quite put it that way in the Nature Reviews DD article… Bayer has a couple PDB’s deposited for Sorafenib / BAY439006 / Nexavar (RAF; 1UWH, 1UWJ), but if you want a Urea bound to VEGF all you’ve got is 1YWN. Does this mean GSK > SKB? I tend to think US20060241149 will put an answer to that.

Yah yah 1YWN was a GSK Japan offering, while the current application is a King of Prussia SKB claim but what’s this new application all about? Mmmmm, I think you’re going to have to do better then a little TIE2 activity to make me a believer.

So I here you thinking, ‘aww, c’mon the Piperazines are cool!’ Bleh, been there done that – and the fused 5? Yah, yah I guess but hasn’t somebody already been there? I hope this is one of those applications dropped just to prevent someone else from going there… Oh, but if you’ve been wondering why you keep seeing these pyridines bearing a 2-methyl carboxamide it’s because if the pyridyl binds the hinge, you get a modest bump in activity, and:

O=C(NC3=CC=C(CN4CCN(C)CC4)C(C(F)(F)F)=C3)N(CC5)C(C5=C2)=CC=C2OC1=CC=NC(C(NC)=O)=C1 O=C(NC3=CC=C(Cl)C(C(F)(F)F)=C3)NC(C=C2)=CC=C2OC1=CC=NC(C(NC)=O)=C1


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Posted by kinasepro on October 29, 2006

and DE102005020105. Guten Tag Schering AG,

Further along the road with the thiazolidinones, eh?  I like the title: New thiazolidinone without basic nitrogen, their production and use as drugs

Kinasepro is always happy to see more Plk1 inhibitors, but hey I’ll admit that I haven’t a clue whats going on with these – and now consider an earlier post on your analogous series, ummm, wrong. The only PDBs that give KP a hint as to what could be going on here are from some compounds bound to PI3K: 2A4Z, and 2A5U. O=C(N(CC)/C(S2)=C(C(NCC(F)(F)F)=O)\C#N)/C2=C/C1=C(C)N=CN1 O=C(N(CC)/C(S2)=C(C(NCC#C)=O)\C#N)/C2=C/C1=CC=C(N3CCCC3)C=C1

Posted in Plk1, Schering AG, Uncategorized | Leave a Comment »