title: Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of cyclin D1-CDK4: synthesis, biological evaluation and structure-activity relationships. Part 2.
abstract: The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as cyclin-dependent kinase 4 (CDK4) inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted phenyl groups, 4-[(methylamino)methyl]benzaldehyde (22) and 5-isoindolinecarbaldehyde (24) (6-tert-butylthieno[2,3-d]pyrimidin-4-yl)hydrazone derivatives have been identified. In this paper, the potency, selectivity profile and structure-activity relationships of our synthetic compounds are discussed.
authors.affiliation: Medicinal Chemistry Research Laboratories II, Daiichi Sankyo Co. Ltd, 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan. horiuchi.takao.pi@daiichisankyo.co.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Motoko
authors.initials: M
authors.lastname: Nagata
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Akahane
authors.forename: Kouichi
authors.initials: K
authors.lastname: Uoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D009374:Neoplasms, Experimental; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013876:Thiophenes; D018844:Cyclin-Dependent Kinases