4-(1H-indazol-5-yl)-6-phenylpyrimidin-2(1H)-one analogs as potent CDC7 inhibitors.
A series of 4-(4-hydroxyphenyl)-6-phenylpyrimidin-2(1H)-ones were identified by HTS as inhibitors of CDC7. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus on removing potential metabolic liabilities and improving cellular potency.
Shafer
Cynthia M
CM
Oncology Division, Novartis Institutes of Biomedical Research, 4560 Horton Street, Emeryville, CA 94608, USA. cynthia_shafer@chiron.com
Lindvall
Mika
M
Bellamacina
Cornelia
C
Gesner
Thomas G
TG
Yabannavar
Asha
A
Jia
Weiping
W
Lin
Song
S
Walter
Annette
A
D001665:Binding Sites; D018938:Caco-2 Cells; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007191:Indazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011744:Pyrimidinones / Q000737:chemistry; D013329:Structure-Activity Relationship
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D007191:Indazoles; D011744:Pyrimidinones; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases