Entry into a new class of protein kinase inhibitors by pseudo ring design.
A pyrimidin-4-yl-urea motif forming a pseudo ring by intramolecular hydrogen bonding has been designed to mimic the pyrido[2,3-d]pyrimidin-7-one core structure of a well-established class of protein kinase inhibitors. Potent inhibition of a number of protein kinases was obtained with the first prototype compound synthesized to probe the design concept.
Furet
Pascal
P
Novartis Institutes for BioMedical Research, WKL-136.P.12, CH-4002 Basel, Switzerland. pascal.furet@novartis.com
Caravatti
Giorgio
G
Guagnano
Vito
V
Lang
Marc
M
Meyer
Thomas
T
Schoepfer
Joseph
J
D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000596:Amino Acids; C109647:PD 166285; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011743:Pyrimidines; D014508:Urea