Chemoselectivity of the Reactions of Diazomethanes with 5‐Benzylidene‐3‐phenylrhodanine

Seyfried, Martin S.; Linden, Anthony; Mlostoń, Grzegorz; Heimgartner, Heinz

doi:10.1002/hlca.200900149

Cited by 13 publications

(2 citation statements)

References 78 publications

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“…The key aldo condensation was performed under thermodynamic conditions to yield the more stable Z -isomers . The assignment of this stereochemistry is consistent with literature reports. − …”

Section: Resultssupporting

confidence: 85%

5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

et al. 2012

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Tyrosyl-DNA phosphodiesterase I (Tdp1) is a cellular enzyme that repairs the irreversible topoisomerase I (Top1)-DNA complexes and confers chemotherapeutic resistance to Top1 inhibitors. Inhibiting Tdp1 provides an attractive approach to potentiating clinically used Top1 inhibitors. However, despite recent efforts in studying Tdp1 as a therapeutic target, its inhibition remains poorly understood and largely underexplored. We describe herein the discovery of arylidene thioxothiazolidinone as a scaffold for potent Tdp1 inhibitors based on an initial tyrphostin lead compound 8. Through structure-activity relationship (SAR) studies we demonstrated that arylidene thioxothiazolidinones inhibit Tdp1 and identified compound 50 as a submicromolar inhibitor of Tdp1 (IC₅₀ = 0.87 μM). Molecular modeling provided insight into key interactions essential for observed activities. Some derivatives were also active against endogenous Tdp1 in whole cell extracts. These findings contribute to advancing the understanding on Tdp1 inhibition.

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Section: Resultssupporting

confidence: 85%

5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

et al. 2012

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“…A search of the CSD for the 5-benzylidenerhodanine fragment resulted in 79 hits, of which seven structures have higher values of this interplanar angle than in the presented crystal structures. The highest interplanar angles are 62.15 and 57.37 � , and are observed for a crystal structure with two molecules in the asymmetric unit and containing a methyl substituent at the linker (CSD refcode TUKJUV; Seyfried et al, 2009).…”

Section: Crystal Structure Analysismentioning

confidence: 99%

Architecture of the rings of 5-arylidenerhodanine derivatives versus P-gp inhibition

Nitek,

Szymańska,

Tejchman

et al. 2023

Acta Crystallogr C

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5-Arylidene derivatives of rhodanine show various biological activities. The new crystal structures of five derivatives investigated towards ABCB1 efflux pump modulation are reported, namely, 2-[5-([1,1′-biphenyl]-4-ylmethylidene]-4-oxo-2-thioxothiazolidin-3-yl)acetic acid dimethyl sulfoxide monosolvate, C18H13NO3S2·C2H6OS (1), 4-[5-([1,1′-biphenyl]-4-ylmethylidene]-4-oxo-2-thioxothiazolidin-3-yl)butanoic acid, C20H17NO3S2 (2), 5-[4-(benzyloxy)benzylidene]-2-thioxothiazolidin-4-one, C17H13NO2S2 (3), 4-{5-[4-(benzyloxy)benzylidene]-4-oxo-2-thioxothiazolidin-3-yl}butanoic acid, C21H19NO4S2 (4), and 5-[4-(diphenylamino)benzylidene]-2-thioxothiazolidin-4-one, C22H16N2OS2 (5). Compounds 1 and 3–5 crystallize in the triclinic space group P\overline 1, while 2 crystallizes in the monoclinic space group P21/n, where the biphenyl moiety is observed in two positions (A and B). Two molecules are present in the asymmetric unit of 5 and, for the other four compounds, there is only one molecule; moreover, 1 crystallizes with one dimethyl sulfoxide molecule. The packing of the molecules containing a carboxyl group (1, 2 and 4) is determined by O—H...O hydrogen bonds, while in the other two compounds (3 and 5), the packing is determined by N—H...O hydrogen bonds. Additionally, induced-fit docking studies have been performed for the active compounds to investigate their putative binding mode inside the human glycoprotein P (P-gp) binding pocket.

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Twofold Extrusion Reactions

Guziec

2012

Organic Reactions

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Twofold extrusion reactions are chemical transformations in which two small inorganic molecules or atoms connecting carbon or nitrogen atoms are lost, generating the corresponding carbon‐carbon or carbon‐nitrogen double bonds. These reactions are particularly useful for the preparation of sterically hindered alkenes and imines. The inorganic species liberated in twofold extrusion reactions can be molecular nitrogen, sulfur, selenium, tellurium, sulfur dioxide, sulfur monoxide, carbon dioxide or carbon monoxide. The most common precursors for twofold extrusion reactions are 1,3,4‐thiadiazolines, which thermally extrude molecular nitrogen affording thiiranes. These thiiranes can be readily desulfurized to afford the corresponding alkenes using tertiary phosphines. The corresponding 1,3,4‐selenadiazolines thermally extrude both molecular nitrogen and atomic selenium directly affording alkenes. Alkenes can also be prepared by formal extrusions of molecular nitrogen plus sulfur dioxide or sulfur monoxide. Extremely sterically hindered imines can be prepared by extrusions of molecular nitrogen and sulfur or selenium from in situ generated heterocyclic precursors. Other less common twofold extrusion reactions are also reported. The detailed preparations of the required precursors for the twofold extrusion reactions as well as the mechanisms of these extrusion processes are discussed in this chapter. The utility of twofold extrusion reactions in the preparations of ‘molecular rotors’ and other extremely sterically hindered alkenes is presented. The steric limitations of the twofold extrusion reactions are discussed along with comparisons of these reactions with other alkene‐ and imine‐forming synthetic methods. The Tabular Survey covers material through the end of 2009.

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Chemoselectivity of the Reactions of Diazomethanes with 5‐Benzylidene‐3‐phenylrhodanine

Cited by 13 publications

References 78 publications

5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

5-Arylidenethioxothiazolidinones as Inhibitors of Tyrosyl–DNA Phosphodiesterase I

Architecture of the rings of 5-arylidenerhodanine derivatives versus P-gp inhibition

Twofold Extrusion Reactions

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