1,4-Dihydroindeno[1,2-c]pyrazoles as novel multitargeted receptor tyrosine kinase inhibitors.
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.
Dinges
Jürgen
J
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6217, USA. jurgen.dinges@abbott.com
Ashworth
Kimba L
KL
Akritopoulou-Zanze
Irini
I
Akritopolou-Zanze
Irini
I
Arnold
Lee D
LD
Baumeister
Steven A
SA
Bousquet
Peter F
PF
Cunha
George A
GA
Davidsen
Steven K
SK
Djuric
Stevan W
SW
Gracias
Vijaya J
VJ
Michaelides
Michael R
MR
Rafferty
Paul
P
Sowin
Thomas J
TJ
Stewart
Kent D
KD
Xia
Zhiren
Z
Zhang
Henry Q
HQ
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
D004791:Enzyme Inhibitors; D011720:Pyrazoles; D014508:Urea; D011505:Protein-Tyrosine Kinases