2-Amino- and 2-Alkylthio-4H-3,1-benzothiazin-4-ones: Synthesis, Interconversion and Enzyme Inhibitory Activities

Häcker, Hans-Georg; Grundmann, Florian; Lohr, Friederike; Ottersbach, Philipp A.; Zhou, Jing; Schnakenburg, Gregor; Gütschow, Michael

doi:10.3390/molecules14010378

Cited by 21 publications

(10 citation statements)

References 54 publications

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“…A related process uses 2‐aminobenzyl or 2‐( N ‐acylamino)benzyl alcohols as starting materials 4, 5. In the cyclization reaction leading to 4 H ‐3,1‐benzothiazin‐4‐ones 2‐thioureido derivatives of benzoates, benzoic acids, benzamides, and dithiocarbamates were applied 6, 7. Another strategy involves the cycloaddition of thiones to conveniently functionalized ketenimines 8–10.…”

Section: Introductionmentioning

confidence: 99%

“…Biological activities of 4 H ‐3,1‐benzothiazines and heterocyclic‐fused analogues have been investigated less extensively 25. There has been identified 2‐amino‐ and 2‐alkylthio‐4 H ‐3,1‐benzothiazin‐4‐ones as selective inhibitors of human cathepsin L and human leukocyte elastase 7. The other examples include 6‐thiaoxanosines, imidazo[1,5‐ a ][1,3]thiazin‐7(3 H )‐one ribosides with strong antiviral and anticancer properties 26, 2‐arylamino substituted thieno[1,3]thiazin‐4‐ones, and analogues of [1,3]thiazino[5,4‐ b ]indole‐4‐one as inhibitors of HLE 27, 28.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Anticancer Activity of New 2‐Aryl‐4H‐3,1‐benzothiazines

Niewiadomy

Matysiak

Karpińska

2011

Archiv der Pharmazie

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New compounds of 2-aryl-4H-3,1-benzothiazine set were synthesized and tested for their antiproliferative activity as part of our research in the antitumor field. The title compounds were obtained by the reaction of aryl-modified sulfinylbis((2,4-dihydroxyphenyl)methanethione) with 2-aminobenzyl alcohols. The reaction proceeded through thiobenzanilide intermediates, which were converted to the 4H-3,1-benzothiazine fused ring by an endocyclization process. The structures of compounds were identified from elemental, IR, (1) H-NMR, (13) C-NMR, and MS spectra analyses. The cytotoxicity in vitro against four human cancer cell lines was determined. The antiproliferative properties of some compounds were more beneficial than cisplatin studied comparatively.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticancer Activity of New 2‐Aryl‐4H‐3,1‐benzothiazines

Niewiadomy

Matysiak

Karpińska

2011

Archiv der Pharmazie

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“…Alkylation and / or benzylation of benzothiazinone derivative 1 with methyl iodide in presence of potassium hydroxide and / or benzyl chloride in acetone containing anhydrous potassium carbonate afforded S‐methylated 13 and/or S‐benzylated derivative 14 , respectively. 2‐(Methylthio)‐4 H ‐benzo[d][1,3]thiazin‐4‐one (13) could be prepared from one pot three component reaction between anthranilic acid, carbon disulfide and methyl iodide in presence of triethylamine as a basic catalyst …”

Section: Resultsmentioning

confidence: 99%

“…The solid product was collected by filtration, dried, and recrystallized from ethanol to give 13 as orange crystals, yield 61% mp 52–53°C lit. mp 54–56°C …”

Section: Methodsmentioning

confidence: 99%

Synthesis and cytotoxic activity against human tumor cells of heterocyclic systems derived from 2‐thioxo‐1,2‐dihydro‐4H‐3,1‐benzothazin‐4‐one

Khlosy

Salem

Ali

et al. 2019

Journal of Heterocyclic Chem

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The title compound was prepared and converted to 2-hydrazinyl-1,2-dihydro-4H-benzo[d] [1,3]thiazin-4-one which was utilized to synthesize fused heterocyclic systems, namely benzotriazolothiazinone derivatives, as well as, nonfused heterocyclic systems such as pyrazolyl-benzothiazinones, benzothiazinylpyridazine and imidazolylbenzothiazinone derivatives via reaction with formamide, acetic acid, ethyl cyanoacetate, maleic anhydride and benzaldehyde followed by treatment with glycine, respectively. All compounds have been structurally characterized by means of IR, MS, and 1 H-NMR spectra. The synthesized compounds were evaluated in vitro for their antiproliferative activity against HePG-2 and MCF-7 cell lines. 2H-Benzo[d][1,3]thiazine-2,4 (1H)-dithione and 2-thioxo-1,2-dihydro-4H-benzo[d] [1,3]thiazin-4-one were the most potent against the two cancer cells compared to that of the reference compound doxorubicin. Most of the synthesized compounds also exhibited good cytotoxic activity.

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“…On the other hand, Gütschow's group prepared a series of 2‐aminobenzothiazinones and none exhibited HNE inhibition; nevertheless, two 2‐alkylthiobenzothiazinones were identified as HNE inhibitors with IC 50 values in the low micromolar range ( 19 , Fig. ) …”

Section: Acylating Inhibitorsmentioning

confidence: 99%

Targeting COPD: advances on low‐molecular‐weight inhibitors of human neutrophil elastase

Lucas

Costa

Guedes

et al. 2011

Medicinal Research Reviews

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Chronic obstructive pulmonary disease (COPD) is a major increasing health problem and the World Health Organization (WHO) reports COPD as the fifth leading cause of death worldwide. COPD refers to a condition of inflammation and progressive weakening of the structure of the lung as well as irreversible narrowing of the airways. Current treatment is only palliative and no available drug halts the progression of the disease. Human neutrophil elastase (HNE) is a serine protease, which plays a major role in the COPD inflammatory process. The protease/anti-protease imbalance leads to an excess of extracellular HNE hydrolyzing elastin, the structural protein that confers elasticity to the lung tissue. Although HNE was identified as a therapeutic target for COPD more than 30 years ago, only Sivelestat (ONO-5046), an HNE inhibitor from Ono Pharmaceutical, has been approved for clinical use. Nevertheless, Sivelestat is only approved in Japan and its development in the USA was terminated in 2003. Other inhibitors in pre-clinical or phase I trials were discontinued for various reasons. Hence, there is an urgent need for low-molecular-weight synthetic elastase inhibitors and the present review discusses the recent advances on this field covering acylating agents, transition-state inhibitors, mechanism-based inhibitors, relevant natural products, and major patent disclosures.

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2-Amino- and 2-Alkylthio-4H-3,1-benzothiazin-4-ones: Synthesis, Interconversion and Enzyme Inhibitory Activities

Cited by 21 publications

References 54 publications

Synthesis and Anticancer Activity of New 2‐Aryl‐4H‐3,1‐benzothiazines

Synthesis and Anticancer Activity of New 2‐Aryl‐4H‐3,1‐benzothiazines

Synthesis and cytotoxic activity against human tumor cells of heterocyclic systems derived from 2‐thioxo‐1,2‐dihydro‐4H‐3,1‐benzothazin‐4‐one

Targeting COPD: advances on low‐molecular‐weight inhibitors of human neutrophil elastase

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