title: Synthesis of potent oxindole CDK2 inhibitors.
abstract: A series of oxindole CDK2 inhibitors was synthesized. These novel analogues have a saturated monosubstituted cyclic moiety at their C-4 position that mimics the ribofuranoside of ATP. This substitution afforded agents with increased potency relative to the parent indolinone and nanomolar range IC(50) against the CDK2 enzyme and two cancer cell lines.
authors.affiliation: Hoffmann-La Roche Inc., 340 Kingsland str., Nutley, NJ 07110-1199, USA. apostolos.dermatakis@roche.com
authors.forename: Apos
authors.initials: A
authors.lastname: Dermatakis
authors.forename: Kin Chun
authors.initials: KC
authors.lastname: Luk
authors.forename: Wanda
authors.initials: W
authors.lastname: DePinto
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012266:Ribose / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D019927:Cyclin E; D004791:Enzyme Inhibitors; D007211:Indoles; D011994:Recombinant Proteins; D012266:Ribose; D000255:Adenosine Triphosphate; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2