Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridinones

Vanelle, Patrice; Castera, Caroline; Crozet, Maxime D.

doi:10.3987/com-04-10285

Cited by 10 publications

(2 citation statements)

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“…The first methylation step was previously reported using dimethyl sulfate (DMS). Here, the reaction time was increased from 1 h to 2 h for an improved yield of compound 1 , which increased from 55 % to 76 % . 1‐Methyl‐5‐nitro‐1 H ‐imidazole ( 1 ) was then alkylated with paraformaldehyde to introduce the hydroxymethyl side chain at the 2‐position …”

Section: Resultsmentioning

confidence: 99%

“…There have been several pharmacomodulation attempts to improve metronidazole activity on parasites such as Giardia intestinalis or Trichomonas vaginalis , and on anaerobic bacteria of the Clostridium and Bacteroïdes species . Previously, we synthesized a 2‐substituted 5‐nitroimidazole by unimolecular radical nucleophilic substitution (S RN 1), RP 57967, which was shown to be fivefold more active than metronidazole against Clostridium perfringens with higher mutagenicity (Figure ) . Extending our research program, we obtained a 4‐substituted 5‐nitroimidazole with a chlorophenylmethylsulfone moiety by vicarious nucleophilic substitution of hydrogen (VNS) .…”

Section: Introductionmentioning

confidence: 96%

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2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

et al. 2019

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Metronidazole is one of the first‐line treatments for non‐severe Clostridium difficile infections (CDI). However, resistance limits its use in cases of severe and complicated CDI. Structure–activity relationships previously described for the 5‐nitroimidazole series have shown that functionalization at the 2‐ and 4‐positions can impart better activity against parasites and anaerobic bacteria than metronidazole. Herein we report the synthesis of new 2,4‐disubstituted 5‐nitroimidazole compounds that show potent antibacterial activity against C. difficile. We used a vicarious nucleophilic substitution of hydrogen (VNS) reaction to introduce a phenylmethylsulfone at the 4‐position and a unimolecular radical nucleophilic substitution (SRN1) reaction to introduce an ethylenic function at the 2‐position of the 5‐nitroimidazole scaffold.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

et al. 2019

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Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridones.

2005

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Fused pyridine derivatives R 0450 Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridones. -An efficient synthesis of title compounds (V) is developed. Interestingly, the tricyclic products can be obtained directly from the precursors (III) bearing the diethyl methylmalonate group at the 2-position. -(CASTERA, C.; CROZET, M. D.; CROZET, M. P.; VANELLE*, P.; Heterocycles 65 (2005) 2, 337-343; Lab. Chim. Org. Pharm., Fac. Pharm., Univ. Mediterr., F-13385 Marseille, Fr.; Eng.) -Mais 24-141

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A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione^® Precursor

Chapuis

Richard

2018

Helvetica Chimica Acta

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Dehydrohedione (DHH) 1a was obtained via a one pot, three step, domino procedure in 54% overall yield from 2a, by treatment with CuBr2, in MeOH at 65 °C. We demonstrated that the direct transformation of malonate derivative 2a into DHH 1a under CuX2 Kochi's conditions goes preferentially through the pathway involving intermediates 2b/2c and 7a, rather than 3a/3b or 8a/8b, essentially via α‐halogenation/dehydrohalogenation of the ketone moiety, both mediated by CuX2, while in‐situ decarbomethoxylation is promoted by the resulting CuX in refluxing MeOH.

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Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridinones

Cited by 10 publications

References 12 publications

2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridones.

A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione^® Precursor

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Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridinones

Cited by 10 publications

References 12 publications

2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

2,4‐Disubstituted 5‐Nitroimidazoles Potent against Clostridium difficile

Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridones.

A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione® Precursor

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A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione^® Precursor