Posted by kinasepro on October 17, 2006
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.