1,4-Dihydroindeno[1,2-c]pyrazoles as novel multitargeted receptor tyrosine kinase inhibitors

Jürgen Dinges; Kimba L Ashworth; Irini Akritopoulou-Zanze; Lee D Arnold; Steven A Baumeister; Peter F Bousquet; George A Cunha; Steven K Davidsen; Stevan W Djuric; Vijaya J Gracias; Michael R Michaelides; Paul Rafferty; Thomas J Sowin; Kent D Stewart; Zhiren Xia; Henry Q Zhang

doi:10.1016/j.bmcl.2006.05.066

1,4-Dihydroindeno[1,2-c]pyrazoles as novel multitargeted receptor tyrosine kinase inhibitors

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4266-71. doi: 10.1016/j.bmcl.2006.05.066. Epub 2006 Jun 12.

Authors

Jürgen Dinges¹, Kimba L Ashworth, Irini Akritopoulou-Zanze, Lee D Arnold, Steven A Baumeister, Peter F Bousquet, George A Cunha, Steven K Davidsen, Stevan W Djuric, Vijaya J Gracias, Michael R Michaelides, Paul Rafferty, Thomas J Sowin, Kent D Stewart, Zhiren Xia, Henry Q Zhang

Affiliation

¹ Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6217, USA. jurgen.dinges@abbott.com

PMID: 16759855
DOI: 10.1016/j.bmcl.2006.05.066

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.

MeSH terms

Amino Acid Motifs
Chemistry, Pharmaceutical / methods
Drug Design
Enzyme Inhibitors / pharmacology
Humans
Hydrogen Bonding
Inhibitory Concentration 50
Microsomes, Liver / metabolism
Models, Chemical
Models, Molecular
Protein-Tyrosine Kinases / antagonists & inhibitors*
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology*
Urea / chemistry

Substances

Enzyme Inhibitors
Pyrazoles
Urea
Protein-Tyrosine Kinases