ArticleJournal of medicinal chemistry2008
Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins.
Article in Journal of medicinal chemistry, 2008. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 71 citations in OpenAlex.
- Review
- Cyclic Dichalcogenides Extend the Reach of Bioreductive Prodrugs to Harness Thiol/Disulfide Oxidoreductases: Applications toACS central science · 2023Article
- Spin Trapping Hydroxyl and Aryl Radicals of One-Electron Reduced Anticancer Benzotriazine 1,4-Dioxides.Molecules (Basel, Switzerland) · 2022Article
- Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells-Are There New Avenues for Treatment?International journal of molecular sciences · 2021Review
- Benzotriazine Di-Oxide Prodrugs for Exploiting Hypoxia and Low Extracellular pH in Tumors.Molecules (Basel, Switzerland) · 2019Article
- Development of [Pharmaceuticals (Basel, Switzerland) · 2019Article
- Schedule-dependent potentiation of chemotherapy drugs by the hypoxia-activated prodrug SN30000.Cancer biology & therapy · 2019Article
- An agent-based model for drug-radiation interactions in the tumour microenvironment: Hypoxia-activated prodrug SN30000 in multicellular tumour spheroids.PLoS computational biology · 2018Article
- Application of Suzuki-Miyaura and Buchwald-Hartwig Cross-coupling Reactions to the Preparation of Substituted 1,2,4-Benzotriazine 1-Oxides Related to the Antitumor Agent Tirapazamine.Journal of heterocyclic chemistry · 2017Article
- Isotopic labeling experiments that elucidate the mechanism of DNA strand cleavage by the hypoxia-selective antitumor agent 1,2,4-benzotriazine 1,4-di-N-oxide.Chemical research in toxicology · 2014Article
- EO9 (Apaziquone): from the clinic to the laboratory and back again.British journal of pharmacology · 2013Review
- Synthesis and biological evaluation of 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives as hypoxic selective anti-tumor agents.Molecules (Basel, Switzerland) · 2012Article
- Discovery and optimization of benzotriazine di-N-oxides targeting replicating and nonreplicating Mycobacterium tuberculosis.Journal of medicinal chemistry · 2012Article
- Six degrees of separation: the oxygen effect in the development of radiosensitizers.Translational oncology · 2011Article
- Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Article
- DNA strand cleaving properties and hypoxia-selective cytotoxicity of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide.Bioorganic & medicinal chemistry · 2010Article
- Redox-directed cancer therapeutics: molecular mechanisms and opportunities.Antioxidants & redox signaling · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
A series of novel tricyclic triazine-di- N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined using pharmacokinetic/pharmacodynamic model predictions of the in vivo hypoxic potency (AUC req) and selectivity (HCD) with 12 TTO analogues predicted to be active in vivo, subject to the achievement of adequate plasma pharmacokinetics.
Indexed as
Identifiers
What OpenQuestion holds
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.