A novel method for heterocyclic amide–thioamide transformations

The chemoselective reactions of 2‐(5‐mercapto‐4‐phenyl‐4H‐[1,2,4]triazol‐3‐ylmethyl)‐6‐p‐tolyl‐4,5‐dihydro‐2H‐pyridazin‐3‐one (3) with different electrophiles were evaluated. Triazole 3 reacted with alkyl halides in the presence of triethylamine in alcohol to give the corresponding S‐substituted derivatives. On the basis of S‐chemoselective reactions of triazole 3, a series of amino acid 10a–d and dipeptide derivatives 12a–d were prepared via azide coupling of the corresponding hydrazides 9 and 15 with amino acid ester hydrochlorides, respectively. N‐Substituted triazoles 6a–c or 7a–d attached to pyridazin‐3‐one moiety were successfully formed by the reaction of 3 with activated acrylic acid derivatives or with amines. Antibacterial activities of the synthesized derivatives were investigated through correlation with Escherichia coli FabH inhibitory activities using molecular modeling docking software. The antimicrobial activity of synthesized compounds was evaluated, showing best inhibition zone for N‐substituted carboxylic acid 5a and N‐substituted nitrile 5c parallel to the molecular modeling studies.

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“…The chemoslective reactions of thioamides have always attracted the attention of our research group .…”

Section: Introductionmentioning

confidence: 99%

Convenient Synthesis of Some Novel Pyridazinone‐Bearing Triazole Moieties

Rayes

Ali

Fathalla

2018

Journal of Heterocyclic Chem

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“…20 However a strong query still remains that is the development of simple, mild and efficient methods for preparation of quinazoline derivatives linked to amino acid residues by a spacer and the evaluation of their biological activities. In view of these facts and in continuation of our efforts in studing the chemoselective reactions of heterocyclic amides [21][22][23] and thioamides, 20,[24][25][26][27][28][29][30][31][32][33][34][35][36][37] we found interesting to synthesize a series of quinazoline derivatives linked to amino acids by a spacer. Here in we wish to report a novel synthesis of 3-arylquinazoline-2,4-dione and use this precursor in the synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate

Ismail¹,

Ali²,

Fathalla³

et al. 2017

Arkivoc

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A series of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate 10-13a-f has been developed on the basis of the N-chemoselective reaction of 3-substituted quinazoline-2,4-diones 3a-d with ethyl chloroacetate and azide coupling method with amino acid ester hydrochloride. The precursor quinazoline diones 3a-d chemoselective reactions were studied using DFT(B3LYP)/6-311G level of theory and were prepared by a new rearrangement method from the corresponding 2-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio) acetohydrazide 6.

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“…Recently, we introduced an interesting thiating reagent: N -cyclohexyl dithiocarbamate cyclohexyl ammonium salt 2 , which was prepared by the reaction of cyclohexyl amine and carbon disulfide at room temperature for 2 h, Scheme 1. 32…”

Section: Resultsmentioning

confidence: 99%

“…This reagent was used as a novel material for heterocyclic amide–thioamide transformations. 32 Thus, our target substrate 3-phenylquinoxaline-2(1 H )-thione ( 5 ) could be simply prepared by thiation of the corresponding 3-phenylquinoxalin-2(1 H )-one ( 3 ) in a two-step reaction: first, chlorination and second , heating chloroquinoxaline 4 with 2 in chloroform for 12 h at 61 °C to afford 5 in excellent yield, Scheme 2. 32…”

Section: Resultsmentioning

confidence: 99%

Convenient Synthesis and Anticancer Activity of Methyl 2-[3-(3-Phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and N-Alkyl 3-((3-Phenyl-quinoxalin-2-yl)sulfanyl)propanamides

et al. 2019

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A series of methyl 2-[3-(3-phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and their corresponding hydrazides and N-alkyl 3-((3-phenylquinoxalin-2-yl)sulfanyl)propanamides were prepared on the basis of the chemoselective Michael reaction of acrylic acid with the parent substrate 3-phenylquinoxaline-2(1H)-thione. The parent thione was produced by a convenient novel thiation method from the corresponding 3-phenylquinoxalin-2(1H)-one. The chemical structures of the newly synthesized compounds were confirmed by elemental analyses, 1H and 13C NMR. The antiproliferative activity of the synthesized compounds was tested against human HCT-116 and MCF-7 cell lines. Out of 25 screened derivatives, 10 active compounds exhibited IC50’s in the range 1.9–7.52 μg/mL on the HCT-116, and 17 active compounds exhibited IC50’s in the range 2.3–6.62 μg/mL on the MCF-7 cell lines compared to the reference drug doxorubicin (IC50 3.23 μg/mL). The structure–activity relationship of the tested compounds was studied through their binding affinity to the human thymidylate synthase allosteric site in silico using molecular docking and proved the quinoxaline ring as a suitable scaffold carrying a peptidomimetic side chain in position 3.

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A novel method for heterocyclic amide–thioamide transformations

Cited by 15 publications

References 38 publications

Convenient Synthesis of Some Novel Pyridazinone‐Bearing Triazole Moieties

Convenient Synthesis of Some Novel Pyridazinone‐Bearing Triazole Moieties

Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate

Convenient Synthesis and Anticancer Activity of Methyl 2-[3-(3-Phenyl-quinoxalin-2-ylsulfanyl)propanamido]alkanoates and N-Alkyl 3-((3-Phenyl-quinoxalin-2-yl)sulfanyl)propanamides

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