CN107488186B - A kind of anti-microbial type compound and its preparation and application - Google Patents
A kind of anti-microbial type compound and its preparation and application Download PDFInfo
- Publication number
- CN107488186B CN107488186B CN201710805789.1A CN201710805789A CN107488186B CN 107488186 B CN107488186 B CN 107488186B CN 201710805789 A CN201710805789 A CN 201710805789A CN 107488186 B CN107488186 B CN 107488186B
- Authority
- CN
- China
- Prior art keywords
- type compound
- preparation
- microbial type
- added
- thiazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Abstract
The present invention relates to a kind of anti-microbial type compound and its preparation and application, the general structures of compound are as follows:R1For H, aryl and fat-based.Preparation: will2- aminoethanethiol hydrochloride, catalyst are added in solvent, and under oxygen atmosphere, in 60~140 DEG C of reaction 6-12h, reaction is finished, and is added water and stirred, and ethyl acetate extracts, and organic phase boils off solvent, and after chromatograph to obtain through column.Preparation manipulation of the present invention is simple, and high income, raw material is cheap and easy to get, and the generation three wastes are few, is produced on a large scale.
Description
Technical field
The invention belongs to drug field, in particular to a kind of anti-microbial type compound and its preparation and application.
Background technique
Over nearly more than 20 years, the infection of gram positive bacteria and drug resistance increasingly increase, and it is each that Diekema in 2001 etc. reports the world
The incidence of state's methicillin-resistant staphylococcus aureus (MRSA), with the Hongkong (74%) in Asia, Japanese (72%), new
Adding slope (62%), Taiwan (61%) is highest, and the Resistance detection of teaching hospital, 5, China in 2005 shows the hair of MRSA
Raw rate average out to 51.3%, highest incidence is Shanghai (78.4%), Hangzhou (60.0%).Currently, the glycopeptide of clinical use
Class antibiotic includes: vancomycin (vancomycin), removes vancomycin (norvancomyxin), teicoplanin
(teicoplanin), Ao Tawan star (oritavancin) and lifting ten thousand stars (telavancin) etc., to gram-positive bacteria
With good inhibitory activity, but simultaneously there is also toxic side effect greatly and lack broad-spectrum antibacterial action the disadvantages of.Not only such as
This, as glycopeptide class (glycopeptides) antibiotic usage increases, vancomycin-resistant enterococcus (VRE), staphylococcus are successive
Occur bringing difficult and challenge to clinical data.Therefore, people still need to find more effective anti-gram-positive bacteria
Drug.The maleimide and 2- methyl-1 that thiamines base replaces, 2,3,9- tetrahydro benzo [b] pyrroles [1,4]-thiazine -1,3- two
Ketone and its derivative are important drug synthesis intermediate, while showing extensive antibacterium, fungi activity, especially to leather
Lan Shi positive bacteria (such as: hay bacillus, staphylococcus aureus etc.) there is stronger inhibitory activity, moreover, Ge Bieyan
Biology has certain inhibitory activity (Tarnavskiy, S.S. to Gram-negative bacteria;Dubinina,G.G.;Golovach,
S.M.;Yarmoluk,S.M..Search for antitumor activity among derivatives of the 2,
5-dihydropyrrole-2,5-dione.Biopolimeri.I.Klitina.2003,19,287-291;Igarashi,Y.;
Watanabe,S.Preparation of 1,4-benzothiazine-2,3-dicarboximides via
intramolecular cyclization of N-substituted 2-[(2-acylaminophenyl)thio]
maleimides and investigation of their antibacterial activity.Nippon.KagakuKa
ishi.1992,11,1392-1396.).Albumen is inhibited to swash in addition, sulphur maleimides class compound is also proved just to have
Enzyme C- α, thus prevent tumor cell drug resistance and reduce cytotoxicity (A.Y.Simonov, S.A.Lakatosh,
Y.N.Luzikov,M.I.Reznikova,O.Y.Susova,A.A.Shtil,S.M.Elizarov,V.N.Danilenko and
M.N.Preobrazhenskaya,Synthesis of 4-substituted 3-[3-(dialkylaminomethyl)
indol-1-yl]maleimides and study of their ability to inhibitprotein kinase C-
α,prevent development of multipledrug resistance of tumor cells and cytotoxi
city.Russ.Chem.Bull.2008,57,2011-2020.).3,4- dihydro -1H- pyrrolo- [3,4-b] [1,4] thiazine -5,
7 (2H, 6H)-diketone are a kind of unknown noval chemical compound, analog 1,2,3,9- tetrahydro benzo [b] pyrroles's [Isosorbide-5-Nitrae]-thiazine -1,
The synthetic method of 3- diketone is simultaneously not suitable for, and with reaction step is more, low yield, substrate applicability is narrow, environmental pollution is serious
The problems such as.
Summary of the invention
It is of the invention technical problem to be solved by the invention is to provide a kind of anti-microbial type compound and its preparation and application
Preparation method simple process, is produced on a large scale at low cost, environmental-friendly, high income.
A kind of anti-microbial type compound of the invention, the structural formula of the compound are as follows:Wherein R1For H, virtue
Base or fat-based.
The R1For-H ,-CH3,-Ph or-CH2The structural formula of Ph, compound are respectively as follows:
Title is successively are as follows: 3,4- dihydro -1H- pyrrole
[3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone, 3,4- dihydro -6- methyl-1 H- pyrroles [3,4-b] [1,4] thiazine -5 are coughed up,
7 (2H, 6H)-diketone, 3,4- dihydro -6- phenyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone and 3,4- bis-
Hydrogen -6- benzyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone.
A kind of preparation method of anti-microbial type compound of the invention, comprising:
It will2- aminoethanethiol hydrochloride is dissolved in solvent, and catalyst is added, and is added in the presence of oxygen
Heat is to 60 DEG C~140 DEG C 6~12h of reaction, purification, obtain 3,4- dihydro -1H- pyrrolo- [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H,
6H)-cyclohexadione compounds, i.e. antibacterium, Mycophyta compound;Wherein R is H, aryl or fat-based.
The R1For-H ,-CH3,-Ph or-CH2Ph。
The catalyst is mantoquita.
The catalyst be one of cuprous iodide, cuprous bromide, stannous chloride, copper acetate, copper bromide, copper chloride or
It is several, while oxygen being required to participate in reaction.
It is described2- aminoethanethiol hydrochloride, catalyst molar ratio be 1:1.0~1.5:0.1~
1.0。
It is describedRatio with solvent is 1g:1mL~100mL.
The solvent is polar non-solute.
The polar non-solute is dimethyl acetamide DMA, in dimethylformamide DMF, dimethyl sulfoxide DMSO
It is one or more of.
The purification specifically: add water and stir 3-5min, ethyl acetate extraction, organic phase is dry, column chromatographs.
A kind of application of anti-microbial type compound of the invention, the anti-microbial type compound are anti-thin in preparation prevention or treatment
Application in bacterium, fungal infection disease drug.
Compound 3,4- dihydro -1H- pyrrolo- [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone that the present invention obtains
Class compound is a kind of novel antibacterium, Mycophyta compound, and research finds the compound in vitro to hay bacillus, golden yellow
Color staphylococcus and Escherichia coli etc. have good inhibitory activity.
Simultaneously [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-cyclohexadione compounds are specifically prepared 3,4- pyrrolin of the present invention
Reaction equation are as follows:
The structural formula of 3,4- dihydro -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone:
Fusing point: 234-236 DEG C;
Character: red solid;
The nucleus magnetic hydrogen spectrum data of 3,4- dihydro -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone are as follows:1H
NMR (400MHz, DMSO-d6) δ 2.86-2.88 (m, 2H), 3.53 (dd, J=3.7,8.6Hz, 2H), 7.72 (s, 1H), 10.18
(s,1H).
The nuclear-magnetism carbon modal data of 3,4- dihydro -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone is as follows:13C
NMR(101MHz,DMSO-d6)δ23.04,41.72,90.52,141.57,166.45,169.57.
The structural formula of 3,4- dihydro -6- methyl-1 H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone:
Fusing point: 227-229 DEG C;
Character: red solid;
The nucleus magnetic hydrogen spectrum data of 3,4- dihydro -6- methyl-1 H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
It is as follows:1H NMR (400MHz, DMSO-d6) δ 2.81 (s, 3H), 2.87-2.89 (m, 2H), 3.56 (dd, J=3.8,8.5Hz,
2H),7.91(s,1H).
The nuclear-magnetism carbon modal data of 3,4- dihydro -6- methyl-1 H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
It is as follows:13C NMR(101MHz,DMSO-d6)δ23.15,23.19,41.96,89.09,141.62,165.16,168.46.
The structural formula of 3,4- dihydro -6- phenyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone:
Fusing point: 166-168 DEG C;
Character: red solid;
The nucleus magnetic hydrogen spectrum data of 3,4- dihydro -6- phenyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
It is as follows:1H NMR (400MHz, DMSO-d6) δ 2.96-2.98 (m, 2H), 3.61-3.63 (m, 2H), 7.33 (dd, J=7.4,
17.1Hz, 3H), 7.45 (t, J=7.7Hz, 2H), 8.15 (s, 1H)
The nuclear-magnetism carbon modal data of 3,4- dihydro -6- phenyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
It is as follows:13C NMR(101MHz,DMSO-d6)δ23.18,42.02,89.85,126.51,127.04,128.70,131.97,
141.49,163.74,167.06.
The structural formula of 3,4- dihydro -6- benzyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone:
Fusing point: 160-162 DEG C;
Character: red solid;
The nucleus magnetic hydrogen spectrum data of 3,4- dihydro -6- benzyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
It is as follows:1H NMR (400MHz, DMSO-d6) δ 2.91 (s, 2H), 3.57 (s, 2H), 4.54 (s, 2H), 7.21 (d, J=7.2Hz,
2H), 7.26 (d, J=6.9Hz, 1H), 7.33 (t, J=7.1Hz, 2H), 8.01 (s, 1H)
The nuclear-magnetism carbon modal data of 3,4- dihydro -6- benzyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
It is as follows:13C NMR(101MHz,DMSO-d6)δ23.11,40.23,41.97,89.30,127.16,127.23,128.51,
137.32,141.57,164.79,168.03.
The present invention by one kettle way direct construction thiazine ring, adopting said method prepare 3,4- pyrrolin simultaneously [3,4-b] [1,
4] thiazine -5,7 (2H, 6H)-diketonate product, and the biological activity tests such as antibacterium, fungi are carried out to it, it is good to find
Antibacterium, fungi bioactive molecule, this for prevent and treat as caused by pathogenic bacteria infection etc. a variety of diseases
It is of great significance.
Beneficial effect
(1) compound 3,4- dihydro -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone that the present invention obtains
Class compound is a kind of novel antibacterium, fungal organisms bioactive molecule, can be used for preventing and treating typhoid fever, pneumonia, syphilis, suddenly
A variety of diseases caused by bacterium and fungi such as random and pulmonary tuberculosis;
(2) preparation method of the invention uses the one kettle way of Atom economy, and a step realizes that maleimide C-H is bis- for the first time
Function dough, the method have easy to operate, high income, wide application range of substrates, environmental-friendly and can there is not yet document report
The advantages that large-scale production.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance of compound 3,4- dihydro -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
Hydrogen spectrum;
Fig. 2 is the nuclear magnetic resonance of compound 3,4- dihydro -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone
Carbon spectrum.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Embodiment 1
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.13g (0.01mol), cuprous iodide
0.190g (0.001mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated to 120 DEG C of open stirring 6h,
Reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4- dihydro-
1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 0.60g, yield 35.5%, mp:234-236 DEG C.
Embodiment 2
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.13g (0.01mol), cuprous iodide
0.190g (0.001mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,
4- dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 0.99g, yield 58.2%, mp:234-236 DEG C.
Embodiment 3
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.13g (0.01mol), cuprous iodide
0.380g (0.002mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 1.44g, yield 84.5%, mp:235-236 DEG C.
Embodiment 4
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.13g (0.01mol), cuprous iodide
0.950g (0.005mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 1.29g, yield 75.8%, mp:234-236 DEG C.
Embodiment 5
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), cuprous iodide
0.380g (0.002mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 1.47g, yield 86.4%, mp:233-234 DEG C.
Embodiment 6
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.695 (0.015mol), cuprous iodide
0.380g (0.002mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 1.41g, yield 82.8%, mp:234-236 DEG C.
Embodiment 7
Take N- methylmaleimido 1.11g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), iodine
Change cuprous 0.380g (0.002mol) to be added into 100mL round-bottomed flask, DMA 20mL is then added, is heated to 120 DEG C of oxygen
Protection is lower to stir 6h, and reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs red solid
Body 3,4- dihydro -6- methyl-1 H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 1.48g, yield 80.5%, mp:
227-229℃。
Embodiment 8
Take N-phenylmaleimide 1.73g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), iodine
Change cuprous 0.380g (0.002mol) to be added into 100mL round-bottomed flask, DMA 20mL is then added, is heated to 120 DEG C of oxygen
Protection is lower to stir 6h, and reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs red solid
Body 3,4- dihydro -6- phenyl -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 2.16g, yield 87.9%, mp:
166-168℃。
Embodiment 9
Take N- benzyl maleimide 1.87g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), iodine
Change cuprous 0.380g (0.002mol) to be added into 100mL round-bottomed flask, DMA 20mL is then added, is heated to 120 DEG C of oxygen
Protection is lower to stir 6h, and reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs red solid
Body 3,4- dihydro -6- benzyl -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 1.97g, yield 75.6%, mp:
160-162℃。
Embodiment 10
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), copper chloride
0.341g (0.002mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 0.67g, yield 39.5%, mp:234-236 DEG C.
Embodiment 11
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), stannous chloride
0.198g (0.002mol) is added into 100mL round-bottomed flask, and DMA 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 0.91g, yield 53.6%, mp:234-236 DEG C.
Embodiment 12
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), cuprous iodide
0.380g (0.002mol) is added into 100mL round-bottomed flask, and DMF 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 1.12g, yield 65.7%, mp:235-236 DEG C.
Embodiment 13
Take maleimide 0.97g (0.01mol), 2- aminoethanethiol hydrochloride 1.356 (0.012mol), cuprous iodide
0.380g (0.002mol) is added into 100mL round-bottomed flask, and DMSO 20mL is then added, and is heated under 120 DEG C of oxygen protections
6h is stirred, reaction is finished, and water 50mL is added, and is stirred 5 minutes, and ethyl acetate extraction, organic phase is dry, and column chromatographs to obtain red solid 3,4-
Dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone 0.72g, yield 42.5%, mp:234-236 DEG C.
Embodiment 14
Antibacterial activity in vitro test:
The surveyed bacterial strain of this test includes: staphylococcus aureus, methicillin-resistant staphylococcus aureus, deformation hammer
Bacterium, Escherichia coli, salmonella typhimurium and Pseudomonas aeruginosa.Using serial dilution measurement compound to selected bacterial growth
Inhibiting effect obtains the minimum inhibitory concentration of Compounds Against different strains.Minimum inhibitory concentration (Minimal inhibitory
Concentration, MIC) be drug needed for inhibiting bacterial growth minimum concentration this experiment of selection Ofloxacin and penicillin
As positive control drug.
Test uses bacterium prior to Mueller-Hinton Broth (MHB) culture medium culture to logarithmic phase, will be cultured
Bacterium is diluted to 105CFU/mL concentration with culture medium and is inoculated in 96 porocyte culture plates (final volume is 200 μ L).Sample and
Comparison medicine is dissolved in dimethyl sulfoxide (DMSO), and the ultimate density of DMSO must not be higher than 0.05%.It is obtained using serial dilution
A series of samples concentration is 64~1 μ g/mL, cultivated for 24 hours at 37 DEG C.With microplate reader 650nm survey culture before and after absorbance, root
Minimum inhibitory concentration i.e. MIC value is calculated according to the variation of absorbance.All experiments are parallel to be carried out 3 times.
Antibacterial activity in vitro is studies have shown that 3,4- dihydro -1H- pyrroles [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H)-diketone
Class compound is to staphylococcus aureus, resistant Staphylococcus aureus, streptococcus mutans, Escherichia coli, Salmonella typhimurium
Bacterium and Pseudomonas aeruginosa etc. all have certain inhibitory activity.Selected objective target compound 3,4- dihydro -1H- pyrroles [3,4-b] [1,4]
Thiazine -5,7 (2H, 6H)-diketone MIC is respectively 4.0,16.0,16.0,8.0,32.0 and 32.0 μ g/mL, other compounds 3,
The MIC of 4- dihydro -6- methyl-1 H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone is respectively 64.0, > 64.0,
32.0,32.0,64.0 μ of and > 128.0 g/mL;3,4- dihydro -6- phenyl -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H,
6H)-diketone MIC is respectively > 128.0, > 128.0,64.0, the 64.0, > μ of 128.0 and > 128.0 g/mL;3,4- dihydro -6- benzyl
The MIC of base -1H- pyrroles [3,4-b] [1,4] thiazine -5,7 (2H, 6H)-diketone is respectively 64.0, > 128.0,64.0, > 128.0,
> 128.0 Hes > 128.0 μ g/mL.
Claims (9)
1. a kind of anti-microbial type compound, it is characterised in that: the structural formula of the compound are as follows:Wherein R1For-H ,-
CH3,-Ph or-CH2Ph。
2. a kind of preparation method of anti-microbial type compound as described in claim 1, comprising:
It will2- aminoethanethiol hydrochloride is dissolved in solvent, catalyst is added, and be heated in the presence of oxygen
60 DEG C~140 DEG C 6~12h of reaction, purification, obtain 3,4- dihydro -1H- pyrrolo- [3,4-b] [Isosorbide-5-Nitrae] thiazine -5,7 (2H, 6H) -
Cyclohexadione compounds, i.e. anti-microbial type compound;Wherein R1For-H ,-CH3,-Ph or-CH2Ph。
3. a kind of preparation method of anti-microbial type compound according to claim 2, it is characterised in that: the catalyst is iodine
Change one or more of cuprous, cuprous bromide, stannous chloride, copper acetate, copper bromide, copper chloride.
4. a kind of preparation method of anti-microbial type compound according to claim 2, it is characterised in that: described
2- aminoethanethiol hydrochloride, catalyst molar ratio be 1:1.0~1.5:0.1~1.0.
5. a kind of preparation method of anti-microbial type compound according to claim 2, it is characterised in that:With it is molten
The ratio of agent is 1g:1mL~100mL.
6. a kind of preparation method of anti-microbial type compound according to claim 2, it is characterised in that: the solvent is polarity
Aprotic solvent.
7. a kind of preparation method of anti-microbial type compound according to claim 6, it is characterised in that: the aprotic, polar
Solvent is one or more of dimethyl acetamide, dimethylformamide, dimethyl sulfoxide.
8. a kind of preparation method of anti-microbial type compound according to claim 2, it is characterised in that: the purification is specific
Are as follows: 3-5min is added water and stirred, ethyl acetate extraction, organic phase is dry, column chromatographs.
9. a kind of application of anti-microbial type compound as described in claim 1, it is characterised in that: the anti-microbial type compound is being made
It is standby to prevent or treat the application in bacterial infective diseases drug.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710805789.1A CN107488186B (en) | 2017-09-08 | 2017-09-08 | A kind of anti-microbial type compound and its preparation and application |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710805789.1A CN107488186B (en) | 2017-09-08 | 2017-09-08 | A kind of anti-microbial type compound and its preparation and application |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107488186A CN107488186A (en) | 2017-12-19 |
CN107488186B true CN107488186B (en) | 2019-06-04 |
Family
ID=60652269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710805789.1A Expired - Fee Related CN107488186B (en) | 2017-09-08 | 2017-09-08 | A kind of anti-microbial type compound and its preparation and application |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107488186B (en) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103501615A (en) * | 2011-04-15 | 2014-01-08 | 巴斯夫欧洲公司 | Use of substituted dithiine-dicarboximides for combating phytopathogenic fungi |
CN106117247B (en) * | 2016-06-29 | 2018-02-16 | 东华大学 | A kind of preparation method of the cyclohexadione compounds of 2 methyl 1,2,3,9 tetrahydro benzo [b] pyrroles [1,4] thiazine 1,3 |
-
2017
- 2017-09-08 CN CN201710805789.1A patent/CN107488186B/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN107488186A (en) | 2017-12-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107556227B (en) | 3-amino-4-alkylthio maleimide compound and preparation and application thereof | |
Prakash et al. | Synthesis, characterization and in vitro antimicrobial activity of some novel 5-substituted Schiff and Mannich base of isatin derivatives | |
Mesbah et al. | Synthesis, characterization, spectroscopic studies and antimicrobial activity of three new Schiff bases derived from Heterocyclic moiety | |
Piotto et al. | Small azobenzene derivatives active against bacteria and fungi | |
Singh et al. | Antimicrobial active macrocyclic complexes of Cr (III), Mn (III) and Fe (III) with their spectroscopic approach | |
Prakash et al. | Organoiodine (III) mediated synthesis of 3, 9-diaryl-and 3, 9-difuryl-bis-1, 2, 4-triazolo [4, 3-a][4, 3-c] pyrimidines as antibacterial agents | |
Asati et al. | Synthesis, characterization and antimicrobial evaluation of some 1, 3-benzothiazole-2-yl-hydrazone derivatives | |
Letafat et al. | Synthesis and antibacterial activity of new N-[2-(thiophen-3-yl) ethyl] piperazinyl quinolones | |
CN106699766B (en) | It is a kind of with the spiral shell isatin β-thiosemicarbazone derivative and its synthetic method of antibacterial activity and application | |
CN107488186B (en) | A kind of anti-microbial type compound and its preparation and application | |
CN109824610B (en) | Chalcone derivative containing quinoxaline, preparation method and application thereof | |
CN109503496A (en) | Pyruvate dehydrogenase system inhibitor class compound and its preparation method and application | |
Zala et al. | Synthesis, characterization, and comparative study of some heterocyclic compounds containing isoniazid and nicotinic acid hydrazide moieties | |
Girdhar et al. | Syntheses and biological studies of novel 9 (10H)-acridone derivatives | |
Nasrullaev et al. | Synthesis and antimicrobial activity of tricyclic quinazolinethiones | |
Bondock et al. | Synthesis and antimicrobial activity of new 4-Methyl-2-(3-pyridyl) thiazolyl chalcones and pyrazolines | |
CN112500347B (en) | Benzazepine seven-membered ring compound, preparation method and application thereof | |
Peng et al. | Design, synthesis, antibacterial activity, and mechanism of novel resveratrol derivatives containing an 1, 3, 4-oxadiazole moiety | |
Seratnahaei et al. | Antimicrobial activities of the secondary metabolite extracted from a Nocardia strain | |
Ghammamy et al. | Preparation and identification of two new phthalocyanines and study of their anti-cancer activity and anti-bacterial properties | |
Rasool et al. | Synthesis, structural elucidation, and antibacterial evaluation of some new molecules derived from coumarin, 1, 3, 4-oxadiazole, and acetamide | |
CORNELI et al. | SCREENING OF HETEROCYCLIC SUBSTITUTED SYDNONES FOR POTENTIAL BIOLOGICAL ACTIVITY | |
Parish et al. | A New Ene-triyne Antibiotic from the Fungus Baeospora m yosura | |
Mohammed | Synthesis, characterization, and antibacterial activity of chalcones derivatives | |
CN104910177B (en) | Aminomethyl triazole-substituted tricyclic fluoroquinolone carboxylic acid derivative and preparation method and application thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190604 Termination date: 20210908 |