ArticleBioorganic & medicinal chemistry2012
Structure-activity relationship of 2,2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, a novel small molecule hypoxia inducible factor-1 (HIF-1) pathway inhibitor and anti-cancer agent.
Article in Bioorganic & medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 35 citations in OpenAlex.
- Immunogenomic Profiling and Classification of Prostate Cancer Based on HIF-1 Signaling Pathway.Frontiers in oncology · 2020Article
- Montelukast inhibits hypoxia inducible factor-1α translation in prostate cancer cells.Cancer biology & therapy · 2018Article
- Biology of advanced uveal melanoma and next steps for clinical therapeutics.Pigment cell & melanoma research · 2015Review
- Crystal structure of 1-(8-meth-oxy-2H-chromen-3-yl)ethanone.Acta crystallographica. Section E, Structure reports online · 2014Article
- Hypoxia inducible factor pathway inhibitors as anticancer therapeutics.Future medicinal chemistry · 2013Review
- Arylsulfonamide KCN1 inhibits in vivo glioma growth and interferes with HIF signaling by disrupting HIF-1α interaction with cofactors p300/CBP.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- 8-Meth-oxy-2H-chromene-3-carbaldehyde.Acta crystallographica. Section E, Structure reports online · 2012Article
- Binding Model for the Interaction of Anticancer Arylsulfonamides with the p300 Transcription Cofactor.ACS medicinal chemistry letters · 2012Article
- Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, novel, small-molecule hypoxia inducible factor-1 pathway inhibitors and anticancer agents.Journal of medicinal chemistry · 2012Article
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6 authors at 1 institution in 1 country.
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Abstract
We have discovered that 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, a novel small molecule HIF-1 pathway inhibitor, can antagonize tumor growth in animal models of cancer, but the treatment necessitates its delivery in a formulation, due to poor water solubility (<15 μg/mL; pH 7.4), evidencing that the chemotype needs further exploration of its amenability to additional chemical modifications for ultimate optimization of function and pharmacology. As a first step towards this goal we investigated the structure-activity relationships of 15 lipophilic 2,2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide to find out strategies of modification. A 3,4-dimethoxybenzenesulfonyl group in region 1 showed the strongest inhibition among five arylsulfonyl groups tested. The presence of propan-2-amine in region 2 conferred the strongest inhibitory effect of the compound on HIF-1 activated transcription in a reporter assay. These findings are important as they help define the structural motifs where the 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide can be chemically modified to improve its pharmacological properties towards development as a cancer therapeutic.
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