Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: synthesis, biological evaluation, and structure-activity relationships.
The synthesis and evaluation of new analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones are described. 2-Pyrdinecarboxaldehyde [6-(tert-butyl)thieno[2,3-d]pyrimidine-4-yl]hydrazone derivatives have been identified as cyclin-dependent kinase 4 (CDK4) inhibitors. The potency, selectivity profile, and structure-activity relationship of this series of compounds are discussed.
Horiuchi
Takao
T
Medicinal Chemistry Research Laboratory II, Daiichi Sankyo Co. Ltd., 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan. horiuchi.takao.pi@daiichisankyo.co.jp
Chiba
Jun
J
Uoto
Kouichi
K
Soga
Tsunehiko
T
D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000037:antagonists & inhibitors*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D006835:Hydrazones; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4