KinasePro

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

Archive for November 6th, 2006

AMG706

Posted by kinasepro on November 6, 2006

Update>> They named it: Motesanib diphosphate

Xcovery has the roundup on AMG706. I tend to think it’s a little apples and oranges to try and line it up against Sutent at this point. Heck it’s been nearly a year since release and noones come out and said Sutent is really any better then Nexavar.

The compound is second generation to ptk787; a VEGF inhibitor which failed to meet a Phase III endpoint.

There’s an article on the preclinical stuff: Cancer Research (2006), 66(17), 8715

Frankly KP is shocked that noone has yet published an application claiming the Bayer modification, woops scratch that, looks like Bayer has an application floating around: WO2006002383, but they don’t have the magic indoline.

ClC(C=C1)=CC=C1NC2=NN=C(C3=C2C=CC=C3)CC4=C=NC=C4 O=C(NC1=CC(NCC2(C)C)=C2C=C1)C(C=CC=N3)=C3NCC4=CC=NC=C4 O=C(C1=NC=CC(CNC2=CC=CC=C2C(NC3=CC=C(OC(F)(F)O4)C4=C3)=O)=C1)NC5CC5

Posted in Amgen, clinical, VEGF | 1 Comment »

US20060247262

Posted by kinasepro on November 6, 2006

Hello Novartis, I see the title of your recent offering is ‘blablabla as inhibitors of Zap70 and / or Syk Kinase.’  The discerning Kinasefan will recognize at least 1/2 of the following molecule which is incidentally makes the highlight reel as example 1. Sure it looks the like the Rigel stuff, but thats really just the part of the game eh? (you guessed it, the 4-halo pyrimidyl’s are part of the table)

COC1=C(OC)C(OC)=CC(NC2=NC(NC3=CC=C(OCCO4)C4=C3S(=O)(N)=O)=CC=N2)=C1

Looking passed the abstract one can learn that yah, sure, some of these examples are going to have some SYK activity (100nM – 10 uM), but primary target is clearly Zap70 and compounds are also tested against ALK.

CNC1=CC(NC2=NC(NC3=CC=C(OCCO4)C4=C3S(=O)(N)=O)=CC=N2)=CC=C1C

I see in the experimental you guys made 1.2 grams of compound 140, and reported the ic50 of 10nM for the compound. I’m not sure why, I mean I’m not entirely sure why you’d drop the dime on that, but clearly it was a lead compound.
CNC1=CC(NC2=NC(NC3=CC=C(OCCO4)C4=C3S(=O)(N)=O)=CC=N2)=CC=C1C CNC1=CC(NC2=NC(NC3=CC=C(OCCO4)C4=C3S(=O)(N)=O)=CC=N2)=CC=C1C

Posted in Novartis, SYK, Zap70 | Leave a Comment »