KinasePro

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

Archive for the ‘RAF’ Category

Biogen Nominated…

Posted by kinasepro on July 14, 2009

… A RAF candidate & Sunesis got a milestone,

In August 2004 the companies entered into a collaboration to discover and develop small molecule cancer therapeutics targeting kinases, a family of cell signaling enzymes that play a major role in the progression of cancer. The research term of this collaboration ended in June of 2008. Sunesis retains an option to participate in the co-development and co-promotion of the Raf kinase inhibitor resulting from this collaboration.

Likely derived from WO/2009/006389WO/2009/006404

O=C(N1)CN(C)CC2=C1N=CN=C2C(N[C@H](C)C3=NC=C(C(NC4=CC(C(F)(F)F)=C(Cl)C=C4)=O)S3)=O

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Posted in Biogen, RAF, Sunesis | 2 Comments »

BAY 73-4506

Posted by kinasepro on May 20, 2009

So Bayer is in Ph2 with fluoro-sorafenib aka DAST, BAY-734506… Only this time they’re in without Onyx and I gather Onyx is none too happy about this.

BAY-734506The distinct compound is claimed in WO/2005/009961 and the I believe the original Sorafenib app is: WO/2000/042012.  What strikes the chemist inventor about a structure like this isn’t usually about who owns it, but if it can really be considered a new invention? The claim structure in the 2000 Sorafenib application can be schematized:

sorafenib-claimsSo for the purpose of this discussion the only meaningful definition is the ring designated as “L” and whether or not they claim the fluoride:

L-definedAnyhow while this structure and their priority date may be vulnerable to obviousness, all of these applications are assigned to Bayer, and not Onyx, so that disagreement will more likely be resolved based on the wording of the Onyx / Bayer contract.  The Onyx press release suggests this very structure was discovered during the collaboration…  We’ll see.  Given the timing I bet someone saw the structure here on Kinasepro and told Onyx, heh.

Posted in Bayer, RAF, VEGF | 5 Comments »

DAST (BAY 73-4506)

Posted by kinasepro on April 7, 2009

It’s Bayer’s Ph2 follow-on to Sorafenib.  VEGF / RAF yadda yadda… Don’t have the structure, but maybe it’s one of these:

O=C(C1=NC=CC(OCC2=C(Cl)C(NC(NC3=CC(C(C)(C)C)=NN3C4=CC=CC(CO)=C4)=O)=CS2)=C1)NC.O=C(C5=NC=CC(OC6=CC=C(NC(NC7=CC=C(Cl)C(C(F)(F)F)=C7)=O)C(F)=C6)=C5)NC

from polymorph apps:

WO/2008/058644 –            WO/2008/079968
WO/2008/043446 –            WO/2008/079972

& yeh, that is Fluoro-Nexavar…

Posted in Bayer, c-Kit, PDGFR, RAF, VEGF | Leave a Comment »

Plexx in the Black

Posted by kinasepro on January 12, 2009

Possibly unaware of a recent nightclub incident, Roche just put a valuation of 60 million up front for PLX-5568: the ph1 Raf inhibitor.  Likely from the aza-indole genre.

Posted in Plexxikon, RAF | 1 Comment »

Arqubraf

Posted by kinasepro on November 5, 2007

Arqule’s bRaf series recently published: WO/2007/123892

O=S(N1CCC[C@H](NC2=NC(C(N(C=CS5)C5=N4)=C4C3=CC=CC(O)=C3)=CC=N2)C1)(C6=CC=C(Cl)C=C6)=O

(Yah, I know the picture is ugly, and the ‘3D’ piperidine is the wrong stereo-isomer… use your imagination)

Posted in RAF | 4 Comments »

WO/2007/084560

Posted by kinasepro on October 27, 2007

Celgene S.D. aka Signal has a series of v600e active thienopyrimidines that also appear to hit the non-kinase PDE4.

ClC1=C(Cl)C=C(C2=NC(N[C@H](CC)CO)=NC3=C2C(N)=C(C(N)=O)S3)C=C1.NC4=C(C(N)=O)SC5=C4C(C6=CC(NC(NC7=CC=C(C(F)(F)F)C=C7)=O)=CC=C6)=NC(NC(C)(C)CN)=N5

WO/2007/084560

(NH2 > S)

Posted in Celgene, RAF | Leave a Comment »

Raf… Weird…

Posted by kinasepro on September 23, 2007

Wyeth’s got some new RAF stuff with US20070219186:

O=C(NC2=CC=CC(C3=CC=NC4=C(C5=CC=C(CN6CCCC6)C=C5)C=NN34)=C2)C1=CC=CC(C(F)(F)F)=C1

data on p19

This one’s got me wondering…

Posted in RAF, Wyeth | 7 Comments »

RAF a la MLNM

Posted by kinasepro on July 4, 2007

US20070149533 is a Raf app from Millennium. I see it as a napthalene – amide cousin to the Birb and Nexavar style ureas. Amgen’s been in the area but not right on top.

O=C(CCN1CCN(C)CC1)NC2=NC=CC(OC3=CC(C=CC(C(NC4=CC(C(C)(C)C)=CC=C4)=O)=C5)=C5C=C3)=C2

Good thing too, b/c you know, I was’t really feeling the whole ‘hydrocinnamides’ thing in US20060160803

Posted in Millenium, RAF | Leave a Comment »

Roche ‘n Raf

Posted by kinasepro on March 19, 2007

US20070060607 is ‘nother thienopyridine application from Roche. The listed in vitro assay uses c-Raf, but selectivity isn’t described.

O=C(C1=CN=C(N)C2=C1SC=C2COC3=C(C)C=CC(NC(C4=CC=C(Cl)C=C4)=O)=C3)NCCO

Posted in RAF, Roche | Leave a Comment »

B-Raf from A-rray

Posted by kinasepro on March 14, 2007

Wo/2007/027855 Matches their earlier Raf kinase application – this time with furanopyridines and some new tail pieces.

O\N=C(CC1)/C(C1=C2)=CC=C2NC3=C(C(NC4CCN(C)CC4)=O)OC5=C3C=CN=C5

Posted in Array, RAF | 1 Comment »