Methyl N-(tert-butoxycarbonyl)pyridine-2-carbimidothioate: A new reagent for the synthesis of N-phenylpyridinecarboxamidine (“arylimidamide”) DNA-minor groove binders from poorly nucleophilic amines

Nué-Martínez, J. Jonathan; Cisneros, David A.; Dardonville, Christophe

doi:10.1016/j.bmcl.2022.128926

Cited by 2 publications

(4 citation statements)

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“…Boc group removal was performed with TFA or with 4 M HCl g –dioxane solution. This protocol also works satisfactorily with different anilines such as 5a , 5h , 8 , 26 9 , and 14 .…”

Section: Resultsmentioning

confidence: 69%

“… 26 We have shown recently that this protocol is useful for the synthesis of bis(arylimidamides) from electron-poor dianilines, where reagent 17 failed to provide the expected products. 26 Using an excess of the reagents and microwave irradiation as the heating source (50 °C, 1 h), 24c – l were obtained smoothly by silica and/or reverse phase chromatography. Boc group removal was performed with TFA or with 4 M HCl g –dioxane solution.…”

Section: Resultsmentioning

confidence: 99%

“…For the synthesis of halogen-containing bis(pyridine-2carboxamidines) 3c−l, dianiline precursors 5c−l were reacted with N-(tert-butoxycarbonyl)pyridine-2-carbimidothioate (21) in the presence of HgCl 2 and Et 3 N (Scheme 3). 26 We have shown recently that this protocol is useful for the synthesis of bis(arylimidamides) from electron-poor dianilines, where reagent 17 failed to provide the expected products. 26 Using an excess of the reagents and microwave irradiation as the heating source (50 °C, 1 h), 24c−l were obtained smoothly by silica and/or reverse phase chromatography.…”

Section: Chemistrymentioning

confidence: 99%

“…A microwave vial was charged with diamine 5c – l (0.4 mmol, 1 equiv, 90–150 mg scale), methyl N -( tert -butoxycarbonyl)pyridine-2-carbimidothioate 26 ( 21 ; 4 equiv), and HgCl 2 (4 equiv). The vial was sealed with a septum cap and purged with argon.…”

Section: Experimental Partmentioning

confidence: 99%

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Synthesis and Biophysical and Biological Studies of N-Phenylbenzamide Derivatives Targeting Kinetoplastid Parasites

Nué-Martinez,

Cisneros,

Moreno-Blázquez

et al. 2023

J. Med. Chem.

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The AT-rich mitochondrial DNA (kDNA) of trypanosomatid parasites is a target of DNA minor groove binders. We report the synthesis, antiprotozoal screening, and SAR studies of three series of analogues of the known antiprotozoal kDNA binder 2- ((4-(4-((4,5-Bis(2-aminoimidazolines) (1) and bis(2-aminobenzimidazoles) (2) showed micromolar range activity against Trypanosoma brucei, whereas bisarylimidamides (3) were submicromolar inhibitors of T. brucei, Trypanosoma cruzi, and Leishmania donovani. None of the compounds showed relevant activity against the urogenital, nonkinetoplastid parasite Trichomonas vaginalis. We show that series 1 and 3 bind strongly and selectively to the minor groove of AT DNA, whereas series 2 also binds by intercalation. The measured pK a indicated different ionization states at pH 7.4, which correlated with the DNA binding affinities (ΔT m ) for series 2 and 3. Compound 3a, which was active and selective against the three parasites and displayed adequate metabolic stability, is a fine candidate for in vivo studies.

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“…Boc group removal was performed with TFA or with 4 M HCl g –dioxane solution. This protocol also works satisfactorily with different anilines such as 5a , 5h , 8 , 26 9 , and 14 .…”

Section: Resultsmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%