CN107098897A - N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides and its medical usage - Google Patents
N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides and its medical usage Download PDFInfo
- Publication number
- CN107098897A CN107098897A CN201610099154.XA CN201610099154A CN107098897A CN 107098897 A CN107098897 A CN 107098897A CN 201610099154 A CN201610099154 A CN 201610099154A CN 107098897 A CN107098897 A CN 107098897A
- Authority
- CN
- China
- Prior art keywords
- thiazol
- piperonyls
- dinitrobenzamides
- acceptable salt
- pharmaceutical composition
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses (5- piperonyls the thiazol-2-yl) -3,5- dinitrobenzamides of the N- shown in a class chemical structural formula I and its pharmaceutically acceptable salt：Wherein, R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl.N- (the 5- piperonyls thiazol-2-yl) application of -3,5- dinitrobenzamides and its pharmaceutically acceptable salt and pharmaceutical composition in anticarcinogen is prepared.
Description
Technical field
The present invention relates to the preparation method of a class noval chemical compound and application, specifically N- (5- piperonyls thiazol-2-yl) -3,5- dinitros
The synthesis of yl-benzamide is with being used as the application for preparing anticarcinogen.
Background technology
Hu Aixi describes N- (the 4- tert-butyl group -5- benzyls thiazol-2-yl) acid amides and the 4- tert-butyl groups -5- (2- nitro-ethyls) -2-
Acylaminothiazole derivatives and its application [CN103333132B, the 2015.3.25 as anticarcinogen；CN103601697B,
2015.3.25]：
The content of the invention
Present invention solves the technical problem that being to provide a class N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides, its system
Preparation Method, pharmaceutical composition and medical usage.
To solve the technical problem of the present invention, the present invention provides following technical scheme：
The first aspect of technical solution of the present invention is to provide N- (5- piperonyls thiazol-2-yl) -3,5- shown in chemical structural formula I
Dinitrobenzamide and its pharmaceutically acceptable salt：
Wherein, R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl.
Further, outstanding compound is selected from N- (5- piperonyl -4- tertiary butyl thiazole -2- bases) -3,5- dinitrobenzamides.
The second aspect of technical solution of the present invention there is provided N- (5- piperonyls thiazol-2-yl) -3,5- two described in first aspect
The preparation method of nitrobenzamide, it is characterised in that its preparation reaction is as follows：
Wherein, R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl.
The third aspect of technical solution of the present invention is to provide containing compound described in first aspect and its pharmaceutically acceptable salt
Pharmaceutical composition, the pharmaceutical composition contains N- (5- piperonyls thiazol-2-yl) -3,5- dinitros of the invention of therapeutically effective amount
Yl-benzamide and its pharmaceutically acceptable salt, and optional contain pharmaceutical carrier.Wherein described pharmaceutical carrier refers to medicine
The conventional pharmaceutical carrier in field；The pharmaceutical composition can be prepared according to method well known in the art.Can be by by the present inventionization
Compound and its pharmaceutically acceptable salt and one or more pharmaceutically acceptable solids or liquid excipient and/or assistant agent group
Close, any formulation used suitable for human or animal is made.The compounds of this invention and its pharmaceutically acceptable salt are in its medicine group
Content in compound is usually 0.1%~95% percentage by weight.
The compounds of this invention and its pharmaceutically acceptable salt or pharmaceutical composition containing it can be administered in a unit,
Method of administration can be enteron aisle or non-bowel, such as oral, intravenous injection, intramuscular injection, hypodermic injection, nasal cavity, oral mucosa,
Eye, lung and respiratory tract, skin, vagina, rectum etc..
Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be that solution is (including true
Solution and colloidal solution), emulsion (including o/w types, w/o types and emulsion), supensoid agent, injection (including liquid drugs injection,
Powder-injection and transfusion), eye drops, nasal drop, lotion and liniment etc.；Solid dosage forms can be tablet (including ordinary tablet,
Enteric coatel tablets, lozenge, dispersible tablet, chewable tablets, effervescent tablet, oral disnitegration tablet), capsule (including hard shell capsules, soft capsule,
Capsulae enterosolubilis), granule, powder, micropill, dripping pill, suppository, film, paster, the agent of gas (powder) mist, spray etc.；
Semisolid dosage form can be ointment, gel, paste etc..
It is sustained release preparation, controlled release system that the compounds of this invention and its pharmaceutically acceptable salt, which can be made ordinary preparation, also be made,
Agent, targeting preparation and various particulate delivery systems.
In order to which the compounds of this invention and its pharmaceutically acceptable salt are made into tablet, it can widely use well known in the art each
Plant excipient, including diluent, binder, wetting agent, disintegrant, lubricant, glidant.Diluent can be starch,
Dextrin, sucrose, glucose, lactose, mannitol, sorbierite, xylitol, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate,
Calcium carbonate etc.；Wetting agent can be water, ethanol, isopropanol etc.；Adhesive can be starch slurry, dextrin, syrup, honey,
Glucose solution, microcrystalline cellulose, mucialga of arabic gummy, gelatine size, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl
Methylcellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol etc.；Disintegrant
Can be dried starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, PVPP, cross-linked carboxymethyl fibre
The plain sodium of dimension, sodium carboxymethyl starch, sodium acid carbonate and citric acid, polyoxyethylene sorbitol fatty acid ester, dodecyl sodium sulfonate
Sodium etc.；Lubricant and glidant can be talcum powder, silica, stearate, tartaric acid, atoleine, poly- second two
Alcohol etc..
Tablet can also be further made to coating tablet, such as sugar coated tablet, thin membrane coated tablet, enteric coated tablets, or it is double-deck
Piece and multilayer tablet.
In order to which administration unit is made into capsule, can by active ingredient the compounds of this invention and its pharmaceutically acceptable salt with
Diluent, glidant mixing, mixture is placed directly within hard shell capsules or soft capsule.Also can be by active ingredient chemical combination of the present invention
Thing and its pharmaceutically acceptable salt are first made particle or micropill with diluent, binder, disintegrant, then be placed in hard shell capsules or
In soft capsule.Each diluent, binder, wetting for preparing the compounds of this invention and its pharmaceutically acceptable salt tablet
Agent, disintegrant, glidant kind can also be used for preparing the capsule of the compounds of this invention and its pharmaceutically acceptable salt.
For the compounds of this invention and its pharmaceutically acceptable salt are made into injection, water, ethanol, isopropanol, third can be used
Glycol or their mixture as solvent simultaneously add appropriate solubilizer commonly used in the art, cosolvent, pH adjustments agent, infiltration
Press conditioning agent.Solubilizer or cosolvent can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin etc.；PH adjusts agent can
To be phosphate, acetate, hydrochloric acid, sodium hydroxide etc.；Osmotic pressure regulator can be sodium chloride, mannitol, glucose,
Phosphate, acetate etc..Freeze drying powder injection is such as prepared, mannitol, glucose etc. can be also added as proppant.
In addition, if desired, colouring agent, preservative, spices, flavouring or other additions can also be added into pharmaceutical preparation
Agent.
To reach medication purpose, strengthen therapeutic effect, medicine of the invention or pharmaceutical composition can be with any known to prescription
Method is administered.
The fourth aspect of technical solution of the present invention is to provide N- described in first aspect present invention (5- piperonyls thiazol-2-yl) -3,5-
Dinitrobenzamide and its pharmaceutically acceptable salt and third aspect described pharmaceutical composition are in terms of anticarcinogen is prepared
Application.
Further, (5- piperonyls thiazol-2-yl) -3, the 5- dinitrobenzamides of N- described in first aspect present invention and its pharmacy
Upper acceptable salt and third aspect described pharmaceutical composition are preparing the application in anti-cervical cancer prescription face.
Advantageous effects：
N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides of the present invention are a class new construction types with anticancer
The compound of activity.
Embodiment
Following examples are intended to illustrate invention rather than limitation of the invention further.
Embodiment 1
The preparation of N- (5- piperonyl -4- tertiary butyl thiazole -2- bases) -3,5- dinitrobenzamides
0.29g5- piperonyls -4- the tert-butyl groups-thiazolamine, 0.23g3,5- dinitrobenzoic acids, 0.21g N, N'- dicyclohexyls
Carbodiimide (DCC), 0.01g DMAPs (DMAP) and 25mL dichloromethane, react at room temperature 2h,
Filtering, collects filtrate, column chromatography (VPetroleum ether︰ VEthyl acetate=8 ︰ 1) separation, obtain yellow solid 0.22g, yield 45%,
M.p.155~157 DEG C.1H NMR (400MHz, CDCl3) (s, 9H, 3 × CH of δ 1.503), 4.13 (s, 2H, CH2),
5.97 (s, 2H, OCH2O), 6.68 (d, J=8.0Hz, 2H, C6H3), 6.78 (d, J=8.0Hz, 1H, C6H3),
9.16 (s, 1H, C6H3), 9.34 (s, 2H, C6H3)。
Embodiment 2
The antitumor activity of N- (5- piperonyl -4- tertiary butyl thiazole -2- bases) -3,5- dinitrobenzamides and its salt
1. antitumor activity principle
Mtt assay biological activity test is also known as MTT colorimetric methods, is a kind of method for detecting cell survival and growth.MTT
Analytic approach is with living cells metabolin reducing agent tetrazolium bromide [3- (4,5- dimethyl -2- thiazoles) -2,5- diphenyl bromination tetrazoles；3-
(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, MTT] based on.MTT is a kind of energy
Receive the dyestuff of hydrogen atom.The dehydrogenase related to NADP in the cell can turn the MTT of yellow in living cells mitochondria
The first a ceremonial jade-ladle, used in libation (formazon) of insoluble bluish violet is melted into, and dead cell is then without this function.Formazon is dissolved with DMSO
Afterwards, OD value is determined with ELIASA under certain wavelength, can both quantifies the survival rate for measuring cell.According to OD value
Inhibitory action of the change observation sample to tumour cell.
2. antitumor activity is tested
Sample：Embodiment compound.
Cell line：Cervical cancer tumer line Hela (offer of Xiangya Medical College, Zhongnan Univ cell bank).
Reagent：Tetrazolium bromide (MTT), RPMI 1640 culture mediums, NBCS, antibiotic (U.S.'s hero's life
Technology company)；Pancreatin (AMRESCO companies of the U.S.)；96 well culture plates (hero Life Technologies, Inc. of the U.S.)；Diformazan
Base sulfoxide (Sigma Co., USA).
Instrument：HFsafe-1500 types superclean bench, HF151UV types CO2(Shanghai power Shen scientific instrument have incubator
Limit company)；XSP-15C types inverted microscope (the rectangular optical instrument Co., Ltd in Shanghai)；Multiskan MK3 type enzyme marks
Instrument (Thermo companies of the U.S.)；Ultra-pure water preparing instrument (Milli-Q companies of the U.S.).
Experimental implementation：Test of the sample for Hela cells.The experimental implementation process of every kind of cell is identical, once tests
Cheng Zhong, per sample (p.s.) sets 5 concentration gradients (0.010 μm of ol/mL, 0.030 μm of ol/mL, 0.100 μm of ol/mL, 0.300
μm ol/mL and 1.000 μm of ol/mL), each four parallel samples of concentration, every group of experiment is parallel 3 times, and passes through blank group
Control is drawn a conclusion.ELIASA detects each hole OD values, Detection wavelength 570nm.
3. antitumor activity evaluation
1) cell inhibitory rate is calculated：
2)IC50Value is calculated
Sample solution concentration logarithm value and cell inhibitory rate linear regression, half-inhibition concentration of the sample to cell is calculated using software
IC50Value.
N- (5- piperonyl -4- tertiary butyl thiazole -2- bases) -3,5- dinitrobenzamides are for Hela cells
IC50It is 7.7 ± 2.3 μM.
Active testing result shows, N- (5- piperonyl -4- tertiary butyl thiazole -2- bases) -3,5- dinitrobenzamides or its salt for
Cervical cancer cell has good inhibitory activity, available for preparing antineoplastic.
Claims (6)
1. N- (5- piperonyl thiazol-2-yl) -3,5- dinitrobenzamide and its pharmacy of the class as shown in chemical structural formula I
Upper acceptable salt：
Wherein, R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl.
2. N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides described in claim 1 and its pharmaceutically acceptable
Salt, it is characterised in that described compound is selected from：N- (5- piperonyl -4- tertiary butyl thiazole -2- bases) -3,5- dinitro benzene first
Acid amides.
3. the preparation method of N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides described in claim 1, its feature
It is that its preparation reaction is as follows：
Wherein, R definition is as claimed in claim 1.
4. N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides described in claim 1 or 2 and its it can pharmaceutically connect
Application of the salt and pharmaceutical composition received in anticarcinogen is prepared.
5. N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides described in claim 1 or 2 and its it can pharmaceutically connect
Application of the salt and pharmaceutical composition received in medicament for resisting cervical cancer is prepared.
6. available carrier in a kind of pharmaceutical composition, including at least one compound of claim 1 or 2 and pharmaceutics.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610099154.XA CN107098897A (en) | 2016-02-23 | 2016-02-23 | N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides and its medical usage |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610099154.XA CN107098897A (en) | 2016-02-23 | 2016-02-23 | N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides and its medical usage |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107098897A true CN107098897A (en) | 2017-08-29 |
Family
ID=59658436
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610099154.XA Pending CN107098897A (en) | 2016-02-23 | 2016-02-23 | N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides and its medical usage |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107098897A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120172374A1 (en) * | 2010-12-29 | 2012-07-05 | Development Center For Biotechnology | Novel tubulin inhibitors and methods of using the same |
| CN102924400A (en) * | 2012-12-03 | 2013-02-13 | 湖南大学 | N-acyl-4-tertiary butyl-5-benzyl thiazole-2-amine as well as preparation method and application thereof |
-
2016
- 2016-02-23 CN CN201610099154.XA patent/CN107098897A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120172374A1 (en) * | 2010-12-29 | 2012-07-05 | Development Center For Biotechnology | Novel tubulin inhibitors and methods of using the same |
| CN102924400A (en) * | 2012-12-03 | 2013-02-13 | 湖南大学 | N-acyl-4-tertiary butyl-5-benzyl thiazole-2-amine as well as preparation method and application thereof |
| CN103333132A (en) * | 2012-12-03 | 2013-10-02 | 湖南大学 | N-(4-tertbutyl-5-benzyl thiazole-2-yl)amide and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104603123B (en) | Solid-state form of bent Ge Lieting and its production and use | |
| CN108440468A (en) | 2- (benzofuran -5- bases) phenol and its application as anticancer drug | |
| CN105777664B (en) | Carboxylate of 2 (2 benzyl hydrazono-) thiazole 5 and preparation method thereof and medical usage | |
| CN105622558B (en) | Acyl hydrazone derivative of the ring containing benzofuran and preparation method and application | |
| CN105693665B (en) | Hydrazone derivative of the ring containing benzofuran and preparation method thereof and medical usage | |
| CN106938989B (en) | N- (5- benzyls thiazol-2-yl) acetamide derivative and the preparation method and application thereof | |
| WO2019011350A1 (en) | Fenlean (flz) crystal g form, preparation method, and composition and use thereof | |
| WO2020190072A1 (en) | Composition for promoting skin wound healing or skin regeneration, containing (r)-ginsenoside rg3 as active ingredient | |
| CN107987033A (en) | The application of vanillic aldehyde and its isomers in NA inhibitor is prepared | |
| CN105777739B (en) | Naphthylamino thiazole methyl qualone derivative and its medical usage | |
| CN106188030B (en) | N- (5- piperonyls thiazol-2-yl) chlorinated amide derivative | |
| CN107098897A (en) | N- (5- piperonyls thiazol-2-yl) -3,5- dinitrobenzamides and its medical usage | |
| CN105646579B (en) | [base of 2 (1H) quinolinone 3] phenylaminomethyl phosphonate ester as cancer therapy drug application | |
| CN110452110A (en) | A kind of phloroglucinol derivatives natural drug and its preparation method and application | |
| CN105566389B (en) | [base of 2 (1H) quinolinone 3] application of naphthalene AminomethylphosphoniAcid Acid ester as cancer therapy drug | |
| CN108272786A (en) | The medical usage of 1- [3- (benzofuran -5- bases) phenyl] -2- acetone benzoyl hydrazones | |
| CN107459513A (en) | N, the thiazole amine derivative of 4 diphenyl 5 (1,2,4 triazolyl) 2 and its medical usage | |
| CN108530439A (en) | Furoyl amine derivative and the preparation method and application thereof | |
| CN108003152A (en) | 4- phenyl -5- (1,2,4- triazolyls) -2- pridylaminos thiazoles and its medical usage | |
| CN104211709B (en) | The purposes of coptisine Alkaloid derivative and its anti-ulcerative colitis | |
| CN107365308A (en) | N- (5- piperonyls thiazol-2-yl) amide derivatives and its application as antineoplastic | |
| CN107098916B (en) | 7- (pyridine methylene) dihydrofuran and chromanone and the preparation method and application thereof | |
| CN107098898A (en) | Azacyclo-amino thiazole methyl qualone derivative and preparation method and application | |
| CN110229081A (en) | 2,4- dinitrobenzene hydazone derivative and the preparation method and application thereof | |
| CN107118176B (en) | N-(5- benzyl thiazol-2-yl) morpholinyl amide and its medical usage |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170829 |