KinasePro

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

Archive for the ‘GSK3’ Category

WO/2009/035159

Posted by kinasepro on April 13, 2009

Possibly SAR-502250 its a Mitsubishi / Sanofi TPK1/GSK3 inhibitor:

CC1=NOC(C(C=C2)=CC=C2[C@H](OCC3)CN3C(N4C)=NC(C5=NC=NC=C5)=CC4=O)=N1

for Alzheimer’s & Diabetes

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Posted in GSK3, Sanofi-Aventis | 2 Comments »

AZ: More GSK3

Posted by kinasepro on October 11, 2008

Likely backup series.  Pictured: WO/2008/121064, and similar WO/2008/121063

O=C(C1=CC=C(C2=NC3=C(C4=CC=C(OC)C=C4)C(F)=CN=C3N2)C=C1)N5CCN(C)CC5

Previously…

Posted in Astra, GSK3 | Leave a Comment »

AZ’s GSK3 Indolinone

Posted by kinasepro on August 10, 2007

WO/2007/089192 is a use app, and WO/2007/089191 is salt forms application of the pictured GSK3 inhibitor originally from WO/2003/08285.  The YM-231146 / YM-359445 series bears similarity, albeit for Vegf.

N#CC1=CC2=C(NC(/C2=C3C=CC(CN4CCOCC4)=CN\3)=O)C=C1

The PDB used for alignment is 1UV5, and you can also check out AZ’s publicized interest in selective GSK3 inhibition in an ’03 JBC and 1q5k.

Posted in Astra, biotech, GSK3 | 2 Comments »

WO2007011065

Posted by kinasepro on January 28, 2007

Mitsubishi has an app covering the intermediates for their GSK3 Sanofi-Aventis stuff. I still think the spiro compounds are sexier, but the morpholines are further explored so here we have a pretty solid looking asymmetric method to make 2-aryl morpholines via CBS reduction:

FC1=CC=C(C(CCl)=O)C=C1 FC1=CC=C([C@H](O)CCl)C=C1
FC1=CC=C([C@H](O)CNCC2=CC=CC=C2)C=C1 FC1=CC=C([C@H](OC2)CN(CC3=CC=CC=C3)C2=O)C=C1
FC1=CC=C([C@H]2CN(CC3=CC=CC=C3)CCO2)C=C1 FC1=CC=C([C@H]2CNCCO2)C=C1
Route starts on page 79 example 1, 2 & 5 shown here.

Array might have something to say with how novel the approach is, y’know given how they sell the (rac) stuff?

Posted in GSK3, Mitsubishi, Sanofi-Aventis | 2 Comments »

US20070015207

Posted by kinasepro on January 22, 2007

The triazolopyrimidine series hit the street with WO2005012304 where the chemistry was from Belgium, and Jannsen was calling them GSK3 inhibitors. Ahh, ’twas a simpler time… Then in WO/2006076442 they started claiming similar compounds: ‘produce a Fak/Cak enzyme inhibitory effect.’ So a) The series aint none too selective, b) there’s some subtle change that I’m not seeing where they can turn the activity around, c) GSK3 inhibitors ‘produce a fak/cak enzyme inhibitory effect,’ or of course d) I’m way over-thinking this. (yah, there is an indan in the earlier stuff too.)

O=C(NCCN(CC)CC)C1=CC=C(NC2=NC=C(N=NN3C4=CC5=C(CCC5)C=C4)C3=N2)C=C1 N#CCC1=CC(N2N=NC3=CN=C(NC4=CC=C(CN5CCN(C)CC5)C=C4)N=C32)=CC=C1

ClickClick – Beats me…

… but Kemia’s got some (gsk3 inhibitors with the core) in WO2006091737 Read the rest of this entry »

Posted in biotech, GSK3, J&J | Leave a Comment »

Got Spiro?

Posted by kinasepro on January 14, 2007

US20070010539 is a GSK3-beta application. This series goes back to ’01, and the pictured spiro compound hit the streets in ’05. Publications on these? Other then an expert opinion (which my library doesn’t carry) and them naming SAR502250 a preclinical development candidate (also in ‘05), I haven’t seen anything. While I don’t relish posting old news, the novel spiro architecture was enough to make KP lift an eyebrow.

O=C1C=C(C2=CC=NC=C2)N=C3N(C[C@H](O)C4=CC=CC=C4)C5(CCN(C)CC5)CCN31

Only they know if these spiro compounds are the lead structures, but it looks like a well developed chemical series with an interesting story to be told, and since they’re not talking… I will.

Read the rest of this entry »

Posted in GSK3, Mitsubishi, Sanofi-Aventis | Leave a Comment »

US20060241297

Posted by kinasepro on October 27, 2006

Hi again Cyclacel, Good idea to cover the pyridines too. Thanks for giving us the data. And hey, it appears you can walk around the activity wheel a little by varying the amine portion of the aminothiazole, but less then 10-fold over all the CDKs and GSK3 / Aurora? Unless your not showing us your ace, it makes Kinasepro wonder just how selective your PLK1 inhibitors are.


CC(N=C(NCCOC)S3)=C3C1=NC(NC2=CN=C(OC)C=C2)=NC=C1

Posted in Aurora, CDK2, Cyclacel, GSK3 | Leave a Comment »

US20060235065

Posted by kinasepro on October 25, 2006

Wie Gehts Roche Penzeburg?

This doesn’t otherwise strike Kinasepro as a very crowded chemical space, but it looks as though Roche is stepping a little close to Astex toes on this one… Looks as though Astex borrowed the general idea from Aventis, so hey thats just the way it goes I guess.

There’s a handful of PDB’s such as the 2C3K and 2C3L (CHK1) that suggest how these compounds bind to kinases.

Posted in Aurora, CDK2, GSK3, Roche | Leave a Comment »