ArticleJournal of medicinal chemistry2014
Establishment of a structure-activity relationship of 1H-imidazo[4,5-c]quinoline-based kinase inhibitor NVP-BEZ235 as a lead for African sleeping sickness.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- Pharmacophore Identification and Structure-Activity Relationship Analysis of a Series of Substituted Azaindoles as Inhibitors ofJournal of medicinal chemistry · 2024Article
- Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways.Molecules (Basel, Switzerland) · 2020Review
- Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity.RSC medicinal chemistry · 2020Article
- In Vitro and in Vivo Activity of mTOR Kinase and PI3K Inhibitors AgainstMolecules (Basel, Switzerland) · 2020Article
- Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents.PLoS neglected tropical diseases · 2019Article
- The Importance of Collaboration between Industry, Academics, and Nonprofits in Tropical Disease Drug Discovery.ACS infectious diseases · 2018Article
- Acid-Promoted Cascade Reaction of N-(4-Chloroquinolin-3-yl)carbamates with Amines: One-Pot Assembly of Imidazo[4,5-European journal of organic chemistry · 2018Article
- Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites.Frontiers in microbiology · 2018Review
- Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation.European journal of medicinal chemistry · 2017Article
- Novel lead compounds in pre-clinical development against African sleeping sickness.MedChemComm · 2017Review
- In vitro evaluation of imidazo[4,5-c]quinolin-2-ones as gametocytocidal antimalarial agents.Bioorganic & medicinal chemistry letters · 2016Article
- Repurposing strategies for tropical disease drug discovery.Bioorganic & medicinal chemistry letters · 2016Review
- Identification of "Preferred" Human Kinase Inhibitors for Sleeping Sickness Lead Discovery. Are Some Kinases Better than Others for Inhibitor Repurposing?ACS infectious diseases · 2016Article
- Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery.Journal of medicinal chemistry · 2015Article
- EVALUATION OF AROMATIC 6-SUBSTITUTED THIENOPYRIMIDINES AS SCAFFOLDS AGAINST PARASITES THAT CAUSE TRYPANOSOMIASIS, LEISHMANIASIS, AND MALARIA.MedChemComm · 2015Article
- Kinases as druggable targets in trypanosomatid protozoan parasites.Chemical reviews · 2014Review
- Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.PLoS neglected tropical diseases · 2014Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Compound NVP-BEZ235 (1) is a potent inhibitor of human phospoinositide-3-kinases and mammalian target of rapamycin (mTOR) that also showed high inhibitory potency against Trypanosoma brucei cultures. With an eye toward using 1 as a starting point for anti-trypanosomal drug discovery, we report efforts to reduce host cell toxicity, to improve the physicochemical properties, and to improve the selectivity profile over human kinases. In this work, we have developed structure-activity relationships for analogues of 1 and have prepared analogues of 1 with improved solubility properties and good predicted central nervous system exposure. In this way, we have identified 4e, 9, 16e, and 16g as the most promising leads to date. We also report cell phenotype and phospholipidomic studies that suggest that these compounds exert their anti-trypanosomal effects, at least in part, by inhibition of lipid kinases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.