2148-86-9Relevant academic research and scientific papers
A SAR study of novel antiproliferative ruthenium and osmium complexes with quinoxalinone ligands in human cancer cell lines
Ginzinger, Werner,Mühlgassner, Gerhard,Arion, Vladimir B.,Jakupec, Michael A.,Roller, Alexander,Galanski, Markus,Reithofer, Michael,Berger, Walter,Keppler, Bernhard K.
, p. 3398 - 3413 (2012)
A series of ruthenium(II) arene complexes with 3-(1H-benzimidazol-2-yl)-1H- quinoxalin-2-one, bearing pharmacophoric groups of known protein kinase inhibitors, and related benzoxazole and benzothiazole derivatives have been synthesized. In addition, the corresponding osmium complexes of the unsubstituted ligands have also been prepared. The compounds have been characterized by NMR, UV-vis, and IR spectroscopy, ESI mass spectrometry, elemental analysis, and by X-ray crystallography. Antiproliferative activity in three human cancer cell lines (A549, CH1, SW480) was determined by MTT assays, yielding IC50 values of 6-60 μM for three unsubstituted metal-free ligands, whereas values for the metal complexes vary in a broad range from 0.3 to 140 μM. Complexation with osmium of quinoxalinone derivatives with benzimidazole or benzothiazole results in a more consistent increase in cytotoxicity than complexation with ruthenium. For selected compounds, the capacity to induce apoptosis was confirmed by fluorescence microscopy and flow-cytometric analysis, whereas cell cycle effects are only moderate.
Design, structure-activity relationships and in vivo characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: Novel class of receptor tyrosine kinase inhibitors
Renhowe, Paul A.,Pecchi, Sabina,Shafer, Cynthia M.,Machajewski, Timothy D.,Jazan, Elisa M.,Taylor, Clarke,Antonios-McCrea, William,McBride, Christopher M.,Frazier, Kelly,Wiesmann, Marion,Lapointe, Gena R.,Feucht, Paul H.,Warne, Robert L.,Heise, Carla C.,Menezes, Daniel,Aardalen, Kimberly,Ye, Helen,He, Molly,Le, Vincent,Vora, Jayesh,Jansen, Johanna M.,Wernette-Hammond, Mary Ellen,Harris, Alex L.
experimental part, p. 278 - 292 (2009/10/17)
The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy. We report herein a series of potent, orally efficacious 4-amino- 3-benzimidazol-2-ylhydroquinolin-2-one analogues as inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine kinases. Compounds in this class, such as 5 (TKI258), are reversible ATP- competitive inhibitors of VEGFR-2, FGFR-1, and PDGFRβ with IC50 values 0.1 μM. On the basis of its favorable in vitro and in vivo properties, compound 5 was selected for clinical evaluation and is currently in phase I clinical trials.
Combination therapy with CHK1 inhibitors
-
, (2008/06/13)
Compounds of Structure I, and salts, tautomers, stereoisomers, and mixtures thereof may be used in methods of inhibiting checkpoint kinase 1 in subjects, in methods for inducing cell cycle progression, and in methods for increasing apoptosis in cells. Such compounds may be used to prepare pharmaceutical compositions and may be used in conjunction with DNA damaging agents.
Inhibition of FGFR3 and treatment of multiple myeloma
-
, (2008/06/13)
Methods of inhibiting fibroblast growth factor receptor 3 and treating various conditions mediated by fibroblast growth factor receptor 3 are provided that include administering to a subject a compound of Structure I, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I have the following structure where and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting fibroblast growth factor receptor 3 and for use in treating conditions mediated by fibroblast growth factor receptor 3 such as multiple myeloma.
BENZIMIDAZOLE QUINOLINONES AND USES THEREOF
-
Page 299, (2008/06/13)
Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.
Quinolinone derivatives
-
, (2008/06/13)
Organic compounds having the formulas I and II are provided where the variables have the values described herein. Pharmaceutical formulations include the organic compounds or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and may be prepared by mixing the organic compounds or pharmaceutically acceptable salts of the organic compounds with a carrier and water. A method of treating a patient includes administering a pharmaceutical formulation according to the invention to a patient in need thereof.
Quinolinone derivatives
-
, (2008/06/13)
Organic compounds having the formulas I and II are provided where the variables have the values described herein. Pharmaceutical formulations include the organic compounds or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and may be prepared by mixing the organic compounds or pharmaceutically acceptable salts of the organic compounds with a carrier and water. A method of treating a patient includes administering a pharmaceutical formulation according to the invention to a patient in need thereof.
Benzimidazole Condensed Ring Systems. 1. Syntheses and Biological Investigations of Some Substituted Pyridobenzimidazoles
Rida, Samia M.,Soliman, Farid S. G.,Badawey, El-Sayed A. M.,El-Ghazzawi, E.,Kader, O.,Kappe, Thomas
, p. 1087 - 1093 (2007/10/02)
The synthesis of some substituted 3-hydroxy-1-oxo-1H,5H-pyridobenzimidazole-4-carbonitriles and 4-ethyl carboxylates 3 and their O- and N-dialkyl derivatives 5,6 is described. 3-Ethoxy-5-ethyl-2-phenyl-1H,5H-pyridobenzimidazol-1-one 7 was ob
