(2H) 1, 4-benzothiazine compounds as well as preparation method and application thereof

A benzothiazine and compound technology, which is applied in the field of chemical drug preparation, can solve the problems of few reports on the antitumor activity of 1,4-benzothiazine compounds, and achieves great promotion and application potential, low price and simple process. Effect

Active Publication Date: 2015-09-09
SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the research of 1,4-benzothiazine drugs, there are many reports on antibacterial, anti-inflammatory, antihypertensive and other activities, but there are few reports on the anti-tumor activity of 1,4-benzothiazine compounds

Method used

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  • (2H) 1, 4-benzothiazine compounds as well as preparation method and application thereof
  • (2H) 1, 4-benzothiazine compounds as well as preparation method and application thereof
  • (2H) 1, 4-benzothiazine compounds as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Synthesis of compound 1

[0021]

[0022] 10g (74.1mmol, 1.0eq.) of benzothiazole and 11.8mL (93.33mmol, 1.3eq.) of dimethyl acetylene dicarboxylate were refluxed in a solution of methanol (50mL): water (10mL) = 5:1 and reacted overnight , methanol and water were evaporated to dryness, and through solid silica gel column chromatography, the column condition volume ratio of petroleum ether: ethyl acetate=3:1 was the eluent, and the eluted fraction was concentrated to obtain 17.3g of yellow solid target (compound 1), Yield: 79%.

[0023] 1 H NMR (500MHz, CDCl 3 )δ: 8.96(s,1H),7.12-7.06(m,3H),7.04-7.01(m,1H),3.76(s,3H),3.59(s,3H),3.57(s,1H),3.55 (s,1H).; 13 C NMR (125MHz, CDCl 3 )δ: 169.08, 168.50, 158.36, 137.30, 126.71, 125.93, 125.34, 122.28, 110.21, 73.03, 53.73, 51.90, 39.76; MS-ESI m / z: 296.05 [M+H] + .

Embodiment 2

[0024] Embodiment 2: the synthesis of compound 2

[0025]

[0026] The benzothiazole was replaced with 6-bromobenzothiazole, and the synthesis method was the same as that in Example 1 to obtain compound 2 with a yield of 68%.

[0027] 1 H NMR (500MHz, CDCl 3 )δ: 8.71(s, 1H), 7.33(d, J=2.0Hz, 1H), 7.29(dd, J=9.0, 2.0Hz, 1H), 7.07(d, J=8.5Hz, 1H), 6.15( d,J=3.5Hz,1H),4.50(d,J=3.0Hz,1H),3.74(s,3H),3.72(s,3H).; 13 C NMR (125MHz, CDCl 3 )δ: 168.85, 167.13, 161.19, 132.19, 129.50, 129.29, 123.85, 121.40, 118.79, 53.45, 53.44, 50.13, 41.61; MS-ESI m / z: 395.95 [M+Na] + .

Embodiment 3

[0028] Embodiment 3: the synthesis of compound 3

[0029]

[0030] 10g (33.89mmol) compound 1 of Example 1 was dissolved in methanol:hydrochloric acid=3:1 (volume ratio) in 40ml solution and refluxed for four hours, evaporated to dryness of methanol and water, through solid silica gel column chromatography, the column condition volume Petroleum ether: ethyl acetate = 4:1 was the eluent, and the eluted fraction was concentrated to obtain 5.9 g of the target (compound 3) as a yellow solid, with a yield of 65%.

[0031] 1 H NMR (500MHz, CDCl 3 )δ: 7.00 (dd, J = 7.5, 1Hz, 1H), 6.96 (t, J = 7.5Hz, 1H), 6.68 (t, J = 7.5Hz, 1H), 6.62 (d, J = 8Hz, 1H) ,4.71(d,J=4.5Hz,1H),4.26(d,J=4.5Hz,1H),3.76(s,3H),3.59(s,3H).; 13 C NMR (125MHz, CDCl 3 )δ: 170.70, 169.63, 139.55, 127.43, 126.51, 119.03, 115.93, 113.30, 55.63, 53.19, 53.07, 41.47; MS-ESI m / z: 268.06[M+H] + .

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Abstract

The invention discloses (2H) 1, 4-benzothiazine compounds as well as a preparation method and application thereof. The structural formula of the (2H) 1, 4-benzothiazine compounds is shown as formula (1), wherein R1 is H, C1, Br or -OCH3 group, and R2 is methyl or ethyl. The preparation method provided by the invention is simple in process, low in cost and suitable for large-scale production, the source is reliable and stable, the popularization and application potentiality is large, moreover, the antineoplastic activity of the (2H) 1, 4-benzothiazine compounds is strong, and the (2H) 1, 4-benzothiazine compounds have the potential of being further researched and developed into antineoplastic drugs.

Description

technical field [0001] The invention belongs to the field of chemical drug preparation, and in particular relates to a class of (2H)1,4-benzothiazine compounds and a preparation method and application thereof. Background technique [0002] The benzothiazine skeleton is an important class of pharmacophore in medicinal chemistry. Common benzothiazine compounds are 1,2-benzothiazine and 1,4-benzothiazine. At present, there are many studies on 1,2-benzothiazine compounds, among which the Oxicam non-steroidal anti-inflammatory drugs that have been marketed belong to 1,2-benzothiazine drugs. In terms of 1,4-benzothiazine drug research, there are many reports on antibacterial, anti-inflammatory, antihypertensive and other activities, but there are few reports on the anti-tumor activity of 1,4-benzothiazine compounds. Contents of the invention [0003] The first object of the present invention is to provide a class of (2H)1,4-benzothiazine compounds with anti-tumor cell activity...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): C07D279/16A61K31/5415A61P35/00A61P35/02
CPCC07D279/16
Inventor汤勇刘永宏廖升荣
OwnerSOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI