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

Archive for October 24th, 2006


Posted by kinasepro on October 24, 2006

How now Schering-Plough, Nice purvalanol analogs as CDK2 inhibitors.

Anything earthshaking here? Hmm… Not really, but look hard enough, and KP always learns something.

Yep, hadn’t noticed the bromide as an isopropyl isostere before, but this is a continuation from US2006041131, WO2004022559. Schering has been beating on this and other 6-5 purine isosteres for some time (WO2004026877). There’s been plenty of Biotech sniffing around here. Vernalis has a similar CDK series (WO2004087707), and a Bioorg. Med. Chem. Lett. 2005, 863 (appears they’ve dropped the series).  Ono has some c-Jun (WO2005035516) inhibitors on the scafford. So whats new here? Vernalis describes selectivity issues.  Maybe they cracked that nut, otherwise its not obvious to me.
BrC2=C1N(N=C2)C(NC3=CC=NC=C3)=CC(C4CCCNC4)=N1 BrC2=C1N(N=C2)C(NC3=CC=CN=C3)=CC(N4CCC[C@@H]4CO)=N1 CC(C)N2C=NC1=C(NC3=CC(Cl)=CC=C3)N=C(N[C@H]([C@H](C)C)CO)N=C12


Posted in CDK2, Schering-Plough | Leave a Comment »


Posted by kinasepro on October 24, 2006

2BDF, and 2BDJ

These are the SRC / Abl phosphine oxide bearing purines from Ariad. Good stuff with a free bonus link to the published discussion: Chem Biol Drug Des 2006, 46.

OC1=CC=CC(CCN2C=NC3=C2N=C(C4CCCC4)N=C3NC5=CC=C(P(OC)(OC)=O)C=C5)=C1x-ray crystallography, SRC/ABL AP23464 AP23451 CCN2C=NC1=C(NC3=CC=C(P(O)(CP(O)(O)=O)=O)C=C3)N=C(C4CCC(N)CC4)N=C12 CP(C(C=C5)=CC=C5NC1=C(N=CN2CCC3=CC(O)=CC=C3)C2=NC(C4CCCC4)=N1)(C)=O

Posted in biotech, PDB, SRC | Leave a Comment »