Design, Synthesis and Biological Evaluation of a Series of Thioamides as Non-Nucleoside Reverse Transcriptase Inhibitors

Mehanna, Ahmed S.; Belani, Jitendra D.; Kelley, Charles J.; Pallansch, Luke A.

doi:10.2174/157340607782360344

Cited by 16 publications

(12 citation statements)

References 14 publications

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“…R f = 0.40 (silica gel, hexane/EtOAc 6/1). 1 Compounds 3c and 3c′. The compound was purified by flash column chromatography (silica gel, hexane/EtOAc 3/1 → 2/1 → 1/ 1).…”

Section: Organometallicsmentioning

confidence: 99%

Synthesis of Ferrocenyl and Ruthenocenyl Thioamide Derivatives Using a Single-Step Three-Component Reaction

et al. 2013

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The efficient syntheses of various metallocenyl thioamides using a single-step three-component condensation reaction between the commercially available (dimethylaminomethyl)ferrocene or aminomethylferrocene and another organic amine in the presence of elemental sulfur are described. All new organometallic thioamide derivatives were unambiguously characterized by 1 H and 13 C NMR spectroscopy and mass spectrometry. Furthermore, the structures of five ferrocenyl thioamides determined by X-ray crystallography are presented. ■ INTRODUCTIONThioamide is an important and useful functional group in chemistry as well as in biology. Thioamides are not only present in medicinally important molecules but are also used as building blocks for the construction of pharmacologically important molecules containing nitrogen and sulfur heterocycles, 1−4 which ultimately find uses as potent antitumor agents and enzyme inhibitors. 1,5−7 Very recently, the thioamide functionality was utilized as a fluorescent quencher in probes designed to monitor protein folding, function, and protein− protein interactions. 8−10 Additionally, thioamide-functionalized fluorescent dyes were successfully employed as sensors for metal ions. 11−13 The principles of such sensors rely on the selective desulfurization of thioamides by thiophilic metal ions. For example, Chang et al. reported a thioamide−pyrene conjugate for the selective detection of Zr 4+ ion in solution. 12 In the presence of Zr 4+ and H 2 O 2 , the thioamide−pyrene conjugate is desulfurized and generates the corresponding amide−pyrene conjugate. This leads to a switch in fluorescence and hence to a selective detection of the Zr 4+ ion.Since its serendipitous discovery in the 1950s, 14 ferrocene has gained the attention of organic as well as inorganic chemists due to its very unique structure, stability, and attractive electrochemical properties. 15 These characteristics have been employed for catalysis purposes, 16 in material science, 17−19 for biosensing applications, 20,21 and more recently in the field of bioorganometallic chemistry. 22−30 Ferrocene derivatives containing a thioamide functionality directly attached to the cyclopentadienyl ring were shown to be very good auxiliary substituents for the generation of cyclopalladated ferrocene derivatives 31,32 as well as being useful as precursors for the synthesis of various ligands used in asymmetric organic synthesis 33,34 and for the electrochemical detection of anions. 35 Despite this importance, to our surprise, there have been only a few reports in the literature describing the synthesis of ferrocenyl thioamides and, more generally, of organometalliccontaining thioamide derivatives. The reason is most likely related to synthetic difficulties, since, in comparison to purely organic compounds, organometallic complexes are sometimes more sensitive toward certain reagents and reaction conditions.To date, the typical and general routes to prepare ferrocenyl thioamides are the thionation of ferrocenyl amides 35,36 (route A, Scheme 1) or ...

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“…R f = 0.40 (silica gel, hexane/EtOAc 6/1). 1 Compounds 3c and 3c′. The compound was purified by flash column chromatography (silica gel, hexane/EtOAc 3/1 → 2/1 → 1/ 1).…”

Section: Organometallicsmentioning

confidence: 99%

Synthesis of Ferrocenyl and Ruthenocenyl Thioamide Derivatives Using a Single-Step Three-Component Reaction

et al. 2013

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“…The facile synthesis of aminooxoethylcarbamothionates may turn out to be an important route to the potential HIV‐1 transcriptase inhibitors, because this motif was found to be a privileged structure in a series of compounds exhibiting such an antiviral activity . We will further investigate the ways of generalization of such unusual termolecular decyclization reaction, aiming at the synthesis of libraries of potential pharmaceuticals.…”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, no such reactions were known to date. The discovered product of decyclization of a thiozolidinone is an aminooxoethylcarbamothionate, which is a known principal structural motif in HIV‐1 transcriptase inhibitors . The decyclization reaction of thiozolidinones of the b series appears to be a tolerant reaction with respect to the nature of external nucleophiles as well as the secondary substituents on the ring.…”

Section: Resultsmentioning

confidence: 99%

A Controlled Cyclization of Functionalized Thioureas and Unprecedented Termolecular Decyclization of Iminothiazolidinones

et al. 2019

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A series of thiourea derivatives bearing pendant hydroxyl groups was synthesized. These quadruply nucleophilic compounds underwent cyclization reactions with bromoacyl bromides, yielding two isomeric iminothiozolidinones. While the remote hydroxyl group in functionalized thioureas was not directly involved in the cyclization, it allowed us to establish control over the product formation through the choice of temperature and/or solvent. The new mode of temperature‐dependent control over the product distribution was different from the classical kinetic vs thermodynamic control. A number of synthesized iminothiozolidinones underwent an unprecedented termolecular decyclization reaction in the presence of an external nucleophile and a proton to yield aminooxoethylcarbamothionates. In addition to the theoretical importance of this newly discovered reaction, there is also a practical need for these decyclized products as they are known privileged structures in the family of HIV‐1 transcriptase inhibitors.

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“…Thioamide derivatives are found to have numerous biological and pharmaceutically activity, and are frequently used as DNA gyrase inhibitors, cell‐permeable and plasma‐stable peptidomimetic inhibitors and non‐nucleoside reverse transcriptase inhibitors . In addition, thioamides are very useful synthons to synthesize various sulfur‐containing heterocylces, such as thieno[2,3‐b]indoles, thiazoles and benzothiazoles .…”

Section: Introductionmentioning

confidence: 99%

Thioamidation of Arylpropyne Derivatives with Sulfur and Formamides for the Synthesis of Aryl Propanethioamides

Zhang

2020

Asian J Org Chem

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Design, Synthesis and Biological Evaluation of a Series of Thioamides as Non-Nucleoside Reverse Transcriptase Inhibitors

Cited by 16 publications

References 14 publications

Synthesis of Ferrocenyl and Ruthenocenyl Thioamide Derivatives Using a Single-Step Three-Component Reaction

Synthesis of Ferrocenyl and Ruthenocenyl Thioamide Derivatives Using a Single-Step Three-Component Reaction

A Controlled Cyclization of Functionalized Thioureas and Unprecedented Termolecular Decyclization of Iminothiazolidinones

Thioamidation of Arylpropyne Derivatives with Sulfur and Formamides for the Synthesis of Aryl Propanethioamides

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