title: Scaffold oriented synthesis. Part 2: Design, synthesis and biological evaluation of pyrimido-diazepines as receptor tyrosine kinase inhibitors.
abstract: We report the discovery of the pyrimido-diazepine scaffolds as novel adenine mimics. Structure-based design led to the discovery of analogs with potent inhibitory activity against receptor tyrosine kinases, such as KDR, Flt3 and c-Kit. Compound 14 exhibited low nanomolar KDR enzymatic and cellular potencies (IC(50)=9 and 52 nM, respectively).
authors: Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60044, USA.
authors: Vijaya
authors: V
authors: Gracias
authors: Zhiqin
authors: Z
authors: Ji
authors: Irini
authors: I
authors: Akritopoulou-Zanze
authors: Cele
authors: C
authors: Abad-Zapatero
authors: Jeffrey R
authors: JR
authors: Huth
authors: Danying
authors: D
authors: Song
authors: Philip J
authors: PJ
authors: Hajduk
authors: Eric F
authors: EF
authors: Johnson
authors: Keith B
authors: KB
authors: Glaser
authors: Patrick A
authors: PA
authors: Marcotte
authors: Lori
authors: L
authors: Pease
authors: Nirupama B
authors: NB
authors: Soni
authors: Kent D
authors: KD
authors: Stewart
authors: Steven K
authors: SK
authors: Davidsen
authors: Michael R
authors: MR
authors: Michaelides
authors: Stevan W
authors: SW
authors: Djuric
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D020794:Receptor Protein-Tyrosine Kinases; C030986:pyrimidine