Search results for "Phthalazines"
showing 5 items of 5 documents
AMG900 as novel inhibitor of the translationally controlled tumor protein
2020
Abstract Introduction Cancer is one of the leading causes of death worldwide. Classical cytotoxic chemotherapy exerts high side effects and low tumor selectivity. Translationally controlled tumor protein (TCTP) is a target for differentiation therapy, a promising, new therapeutic approach, which is expected to be more selective and less toxic than cytotoxic chemotherapy. The aim of the present investigation was to identify novel TCTP inhibitors. Methods We performed in silico screening and molecular docking using a chemical library of more than 31,000 compounds to identify a novel inhibitor of TCTP. We tested AMG900 in vitro for binding to TCTP by microscale thermophoresis and co-immunoprec…
Benzodiazines: recent synthetic advances.
2017
Benzodiazines (diazonaphthalenes with both nitrogens in the same ring) – cinnolines (1,2-benzodiazine), quinazolines (1,3-benzodiazine), phthalazines (2,3-benzodiazine) and quinoxalines (1,4-benzodiazine) – are important class of compounds with broad biological properties and wide application in pharmaceutical as well as agrochemical arenas. These diazaheterocycles are present in a wide variety of bioactive natural products as well as synthetic molecules that are good drug candidates constituting key structural units responsible for their pronounced therapeutic activities. Their rapidly growing uses and applications in medicinal and agrochemical arenas prompt the researchers for further stu…
Phase II trial of ptk787/zk 222584 (vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or…
2011
ABSTRACT Background The objective of this multicenter, prospective uncontrolled phase II trial was to determine efficacy, safety and tolerability of vatalanib, an oral angiogenesis inhibitor targeting all known vascular endothelial growth factor receptors, in the second-line treatment of non-small-cell lung cancer (NSCLC). Patients and methods Patients with stage IIIB/IV NSCLC-proven tumor progression during or after one platinum-based chemotherapy regimen received a fixed dose of 1250 mg vatalanib either once-daily dosing (QD) or two divided daily dosing (TDD: 500 mg a.m. + 750 mg p.m.) until disease progression or unacceptable toxicity. Primary end point was the disease control rate (DCR)…
Dynamic contrast-enhanced MRI parameters as biomarkers for the effect of vatalanib in patients with non-small-cell lung cancer.
2014
ABSTRACT: Aims: To assess the utility of dynamic contrast-enhanced MRI parameters in the demonstration of early antiangiogenic effects and as prognostic biomarkers in second-line treatment of advanced-stage non-small-cell lung cancer with vatalanib. Patients & methods: The transfer constant (Ktrans) and the initial area under the contrast concentration–time curve at 60 s (AUC60) were assessed in 46 patients. Changes were compared with response evaluation from computed tomography imaging and Response Evaluation Criteria In Solid Tumors guidelines. Results: Statistically significant mean reductions in Ktrans (38.4%; p < 0.0001) and AUC60 (24.9%; p < 0.0001) were found at day 2. Af…
Synthesis and cytotoxic activity of a new potential DNA bisintercalator: 1,4-Bis{3-[N-(4-chlorobenzo[g]phthalazin-1-yl)aminopropyl]}piperazine
2010
The synthesis of new 1,4-bisalkylamino (2-4) and 1-alkylamino-4-chloro (5-6) substituted benzo[g]phthalazines is reported. Compounds 2-4 and 6 were prepared both in the free and heteroaromatic ring protonated forms. Bifunctional 6 contains the 1,4-bisaminopropylpiperazine chain as a linker between the two heteroaromatic units, whereas 5 is its monofunctional analogue. The in vitro antitumour activity of the synthesized compounds has been tested against human colon, breast and lung carcinoma cells, and also against human glioblastoma cells. Results obtained show that all of them are active in all cases, but bifunctional 6·2HCl is remarkably effective against the four cell lines tested, exhib…