title: 1,4-Dihydroindeno[1,2-c]pyrazoles as novel multitargeted receptor tyrosine kinase inhibitors.
abstract: A series of 1,4-dihydroindeno[1,2-c]pyrazoles with a 3-thiophene substituent carrying a urea-type side chain were identified as potent multitargeted (VEGFR and PDGFR families) receptor tyrosine kinase inhibitors. A KDR homology model suggested that the urea moiety is able to interact with a recognition motif in the hydrophobic specificity pocket of the enzyme.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6217, USA. jurgen.dinges@abbott.com
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dinges
authors.forename: Kimba L
authors.initials: KL
authors.lastname: Ashworth
authors.forename: Irini
authors.initials: I
authors.lastname: Akritopoulou-Zanze
authors.forename: Irini
authors.initials: I
authors.lastname: Akritopolou-Zanze
authors.forename: Lee D
authors.initials: LD
authors.lastname: Arnold
authors.forename: Steven A
authors.initials: SA
authors.lastname: Baumeister
authors.forename: Peter F
authors.initials: PF
authors.lastname: Bousquet
authors.forename: George A
authors.initials: GA
authors.lastname: Cunha
authors.forename: Steven K
authors.initials: SK
authors.lastname: Davidsen
authors.forename: Stevan W
authors.initials: SW
authors.lastname: Djuric
authors.forename: Vijaya J
authors.initials: VJ
authors.lastname: Gracias
authors.forename: Michael R
authors.initials: MR
authors.lastname: Michaelides
authors.forename: Paul
authors.initials: P
authors.lastname: Rafferty
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sowin
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Xia
authors.forename: Henry Q
authors.initials: HQ
authors.lastname: Zhang
mesh_terms: D020816:Amino Acid Motifs; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014508:Urea / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D014508:Urea; D011505:Protein-Tyrosine Kinases