Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5443
Title: Synthesis, Modeling, and RET Protein Kinase Inhibitory Activity of 3- and 4-substituted Beta-carbolin-1-ones
Authors: Raffaella, Cincinelli
Giuliana, Cassinelli
Sabrina, Dallavalle
Cinzia, Lanzi
Lucio, Merlini
Botta, Maurizio 
Tiziano, Tuccinardi
Adriano, Martinelli
Sergio, Penco
Franco, Zunino
Issue Date: 2008
Project: None 
Journal: JOURNAL OF MEDICINAL CHEMISTRY
Abstract: 
A series of beta-carbolin-2-ones and 3,10-dihydro-2H-azepino[3,4-b]indol-1-ones have been designed, synthesized, and evaluated as RET protein kinase inhibitors on the basis of their structural similarity with the prototype indolin-2-one RPI-1. Some beta-carbolin-2-ones (structure 2) showed an ability to inhibit RET enzymatic activity in vitro and proliferation of RETC634R oncogene-transformed NIH3T3 cells comparable to that of the reference compound. The docking analysis of the interaction of these compounds with the crystallographic structure of RET tyrosine kinase domain suggested a new binding interaction scheme different from the one proposed during their design. The rigid structure of the compounds of this series represents a new scaffold with potential advantages in the design of RET protein kinase inhibitors.
Description: 
22379
URI: http://hdl.handle.net/20.500.12779/5443
ISSN: 0022-2623
DOI: 10.1021/jm8007823
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