KinasePro

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

Archive for the ‘c-Kit’ Category

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…

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

Masitinib

Posted by kinasepro on April 3, 2009

aka: Masivet, Kinavet & AB-1010 quietly joined the Phase iii club when it went Ph3 back in December.

O=C(NC1=CC=C(C)C(NC2=NC(C3=CC=CN=C3)=CS2)=C1)C4=CC=C(CN5CCN(C)CC5)C=C4

WO/2008/98949

Posted in c-Kit, gleevec, PDGFR, Phase III | 3 Comments »

Re-Engineering Gleevec

Posted by kinasepro on December 5, 2007

Alex Fernandez thinks he has a dehydron in action with Gleevec & c-Kit:

The interest of this goes way beyond this particular drug and this particular side effect. The idea is we could demonstrate for the first time that you can take a drug with side effects and re-engineer it to curb those side effects, Fernandez said in a telephone interview. (Reuters)

Adding a methyl group alpha to the the pyridine will make the activity of most kinases go away given a steric clash with the neighboring carbonyl. It’s interesting that the c-Kit activity stays behind, but the evidence given for the dehydron effect is through molecular dynamics and while as a rule I’ll try not to hold that against them, I don’t believe that the authors give a satisfactory answer as to why this new methyl group does not negate the compounds c-Kit activity through a simple steric interaction.

O=C(C5=CC=C(C=C5)CN4CCN(CC4)C)NC1=CC=C(C(NC2=NC=CC(C3=CC=C(C)N=C3)=N2)=C1)C

J Clin Invest 2007, 117, 4044
related: Cancer Res. 2007, 67 (9): 4028-33

Nippon Shanyaku took the alternate tack of making the core pharmacophore more potent and made it hit other things… In the discovery of the ph1 compound NS-187 (Inno-406):

O=C(NC3=CC=C(C)C(NC4=NC=CC(C5=CN=CN=C5)=N4)=C3)C1=CC=C(CN2C[C@@H](N(C)C)CC2)C(C(F)(F)F)=C1

Read all about it in the ’06 BMCL, the ’07 BMCL, the 2E2B, or through an Open Access offering here.

Posted in c-Kit, gleevec | 7 Comments »

Tasigna

Posted by kinasepro on June 19, 2007

aka nilotinib, AMN-107 is a Novartis’ follow-on to Gleevec.

O=C(NC1=CC(C(F)(F)F)=CC(N2C=C(C)N=C2)=C1)C3=CC=C(C)C(NC4=NC=CC(C5=CC=CN=C5)=N4)=C3

wiki; clinic; WO/2002/022597

Posted in c-Kit, gleevec, Novartis, Phase III | Leave a Comment »

Motesanib

Posted by kinasepro on June 19, 2007

Motesanib diphosphate, AMG-706 hits: Vegfr1,2,3, c-kit, Pdgfr-b, and Ret

O=C(NC1=CC=C(C(C)(C)CN2)C2=C1)C3=CC=CN=C3N([H])CC4=CC=NC=C4

Salt: bisphosphonate
Clinic Ph iii: NSCLC
Cancer Res.; WO/2002/066470

Posted in Amgen, c-Kit, PDGFR, Phase III, VEGF | Leave a Comment »

E7080

Posted by kinasepro on May 29, 2007

O=C(C1=CC2=C(OC3=CC=C(NC(NC4CC4)=O)C(Cl)=C3)C=CN=C2C=C1OC)N

US20070117842 is a polymorph application, and there’s been a fair amount of IP activity around the compound. Indications are its E7080: an oral PhI Vegf, FGF, Pdgf, C-Kit, etc compound which first touched down in WO/2004/080462.

Posted in c-Kit, Eisai, Fgf, PDGFR, VEGF | 2 Comments »

Axitinib

Posted by kinasepro on May 13, 2007

aka AG-013736 is Pfizer’s Vegf / PDGF / cKit inhibitor.

O=C(C1=CC=CC=C1SC2=CC3=C(C(/C=C/C4=NC=CC=C4)=NN3)C=C2)NC

’06 Asco, clinic: ph 2; process app; pct

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

Plexxikon’s cFms/cKit stuff:

Posted by kinasepro on February 10, 2007

Some of Plexxicon’s latest cKit / cFms stuff has published, and surprise-surprise its got their ‘scaffold’. The choice of where to tag on amines suggests the following motif:

ClC1=CC=C(C=C1)CNC2=NC=C(CC3=CNC4=NC=C(OCCN5CCOCC5)C=C43)C=C2

This week: US20070032519
Last week: WO/2007/013896
Last year: WO/2006/009797

Posted in c-fms, c-Kit, Plexxikon | Leave a Comment »

US20060281764

Posted by kinasepro on December 16, 2006

WTF J&J, Oxime-aldehydes? FLT3, TRKb, cKit inhibitors… Shinogi has some related EGF compounds: WO2006106721, and there’s a Biorg Med Chem Lett with the motif in CDK so its not unheard of. Quinazoline isosteres… Cool.

O=C(NC1=CC=C(C(C)C)C=C1)CC2CN(C3=NC=NC(N([H])[H])=C3/C=N/OC)CC2

Update >> There’s a couple other relatives that make this a family of applications which all published last Thursday:

 

O=C(N(CC1)CCC1C2=C(C=CC(N(C)C)=C3)C3=NC=N2)NC4=CC=C(OC(C)C)C=C4

This looks like the primary series, and the aniline appears to dial in TRKB – albeit not all that dramatically: US20060281772

O=C(OC1CN(C2=C3C(C=CS3)=NC=N2)CC1)NC4=CC=C(N5CCCC5)N=C4

US20060281768

 

Hmm… is LG293 TRKb?

 

Posted in c-Kit, Flt3, J&J | 2 Comments »