AS-703026

>> Update – this structure has been revised from the butyl amide – This is (i believe) the correct structure >>

EMD-Serono’s got ‘a ph1 non-hydroxamate ‘ATP Collaborative’ Mek inhibitor.

via Ghost, & WO/2006/045514

R763

Rigel’s Aurora inhibitor R-763 going Ph1 for ‘Hematological Malignancies’. It’s in Ph1 for solid tumors already. hmm… I thought they had to call it ‘EMD Serono’ in USA.  Merck DE # is: AS703569

So it’s looking like: WO/2006/055561 and before that: WO/2005/118544

Neeto – looks like they resolve the enantiomers via:

Even neeter-0 they show a couple xenos

WO20060105865

Hello there Merck KGaA,

Nice Chk1 application. This one’s a modification of a previous GSK application WO2006072354 [Thats glycogen synthase kinase, not glaxo (I know, kinasepro wishes one of them would change their name too)]

This functional group is not without precedent, occuring in BMY25368 a histamine H2-receptor antagonist and elsewhere in the medicinal chemistry patentscape. Notably Schering and Wyeth seem to be all over the functional group for the last 25 years. Not so much in Kinases, but somebody in Pearl River must like them because American Cyanimide, American Home Products, and Wyeth have all messed around with them quite a bit through their history. They describe them as alpha-amino acid isosteres: J. Med. Chem. 1998, 236.

I guess KP shouldn’t be surprised to find the group has been used before for kinase inhibitors. It doesn’t seem like anyone has taken them very far, but OSI has a series of derivatives that hit c-Kit WO2006034111, and Abbott tried to use them as a urea mimic in a series of PP1 analogs: US20040014756.

O=C(C(NC3=CC(C(NC(CN5CCOCC5)=O)=NN4)=C4C=C3)=C1N[C@H](C)C2=CC=CC(O)=C2)C1=O

DE102005015253

Hi Merck KgAa,

Yours is another one of those patent applications that has Kinaspro thinking “this has got to be covered somewhere, by someone”

So did Bayer/Onyx not exemplify the N-Me Carboxamide in their earlier work?

HoHoHo-
Derek Lowe-
Wont’ ya Go-

and… umm… well… Maybe you could just walk down the hall and poke someone in the eye for me?

No, I guess there’s no need for that, they did indeed claim a handful of disubstituted pryazoles. (RAF: WO199932106, WO199932110, WO199932111, and TrkA WO2005110994), Seems to Kinasepro that these partygoers are a few years late particularly when Merck is doing what Bayer did back in 1999, and BI did first with BIRB796 and then also later with (US6492529), hell even Kirin Beer has one of these: (WO2002088110)

Wait did someone say Kirin Beer?

So Merck think’s they’ve found a way around the Bayer patent estate, and must have some kind of PK / CYP / Drug-like-property / selectivity bump that’s not obvious. They’ve got something similar going on in: WO2006040056 where they are clearly looking at one-offs of Nexavar. You have to remember these are those Crazy-evil-genius-brilliant-German Merck types…

Hmmm, so what’s new in these patents? Well, one of the claims is on TIE2, and you can tell by the Markush they are only attempting to make very narrow claims around the two Pyrazole substituents. I didn’t translate all the structure names, but it appears there are a number of furans exemplified with a handful of other R group modifications. The one example they draw a structure for:

Of note Deciphera has 2 similar applications which published in July. WO2006071940, and WO2006081034 they are labelled VEGF/PDGF/Bcr-Abl applications

And the companies with advanced Angiogenesis programs that any potential candidate has to beat:

Bayer……… Check (http://www.nexavar.com)
Pfizer…….. Check (http://www.sutent.com/)
Astra-Zeneca.. Check (http://www.zactima.net/)
Genentech….. Check (http://www.avastin.com)
Bristol-Myers Squibb, Novartis, Glaxo, Roche, Amgen, Kirin Brewing Company, check, check, checkitty, check, check, check – yah, he did say Kirin Beer.

WO2006094600

Hello Crazy Germans, errr I mean Hi Merck KGaA.

While everyone else is making pyrimidines, quinazolines, and assorted one or two-offs here comes Merck with umm this:?

I guess they look a little like the CDK compounds from J. Med. Chem. 2006, 44, 4628, but not really.

Kinaspro’s German isn’t all that good, but it looks as though they too speak Kinese: