CN105017174A - N- (4-alkyl-5-benzyl thiazole-2-base) enoyl-amine and preparation method and application thereof - Google Patents
N- (4-alkyl-5-benzyl thiazole-2-base) enoyl-amine and preparation method and application thereof Download PDFInfo
- Publication number
- CN105017174A CN105017174A CN201510406074.XA CN201510406074A CN105017174A CN 105017174 A CN105017174 A CN 105017174A CN 201510406074 A CN201510406074 A CN 201510406074A CN 105017174 A CN105017174 A CN 105017174A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- preparation
- thiazol
- benzyl
- salt
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to N-(4-alkyl-5-benzyl thiazole-2-base) enoyl-amine or salt thereof, shown as a chemical structure formula I, wherein in the formula I, R is selected from C1-C2 alkyl, C3-C4 straight chains or C3-C4 branched alkyl; Y1 and Y3 are selected from hydrogen, methyl, ethyl, hydroxyl, methoxyl, ethoxyl, fluorine, chlorine, bromine or iodine; Y2 and Y4 are selected from hydrogen, methyl and ethyl; n is selected from 1,2,3,4,5,6 or 7; z is selected from hydrogen, methyl or phenyl; salt is selected from hydrochloride, hydrobromide, sulphate, phosphate, mesylate, benzene sulfonate and itramine tosylate. The invention provides the application of the N-(4-alkyl-5-benzyl thiazole-2-base) enoyl-amine or the salt thereof in preparation of anticancer drugs.
Description
Technical field
The present invention relates to preparation method and the application of new compound, specifically
nthe preparation of-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides with as the application preparing anticarcinogen.
Background technology
Dasatinib (Dasatinib) is a kind of oral multiple receptor tyrosine kinases inhibitor of Bristol-Myers Squibb Co.'s research and development, and commodity are called Shi Dasai (Sprycel).In June, 2006, U.S. FDA approval Dasatinib is used for the past Endodontic failure or all stadium (chronic phase, accelerator, lymphoid lineage cell acute transformation phase and the myelocyte acute transformation phase) patient of Adult chronic's granulocyte leukemia (CML) that do not tolerate, is also used for the treatment of other therapy resistances or the kemia adult patient (Ph+All) of Philadelphia Chromosome Positive that do not tolerate simultaneously.It is the representative in the market in molecular targeted therapy.On May 5th, 2012, Dasatinib goes through in Discussion on Chinese Listed.Can be rapidly absorbed after Dasatinib oral administration, in 0.5-3 hour, reach peak concentration.In patient, the population mean t1/2 of Dasatinib is approximately 5-6 hour.The main adverse reaction of Dasatinib comprises: bone marrow depression (thrombopenia, Neutrophilic granulocytopenia and anaemia), hemorrhage, fluid retention and QT interval prolongation etc.
Holla etc. [European Medical Chemistry, 2003,38:313-318] describe 2-virtue amino-4-(2, the chloro-5-fluorophenyl of 4-bis-) preparation of thiazole and biological activity; Chinese invention patent (CN1018445026, CN101781269) describes 5-(4-chlorophenylmethyl)-4-tertiary butyl thiazole derivatives and the 4-tertiary butyl-2-(nitrobenzyl imino-) thiazole preparation and as the application preparing antitumor drug.Chinese invention patent (CN101277692A, 2008.10.01 are open) describes the preparation of 5-benzyl-4-methyl/trifluoromethyl-2-virtue aminothiazole.(CN102070556A, 2011.5.25 are open for Chinese invention patent; CN102067845A, 2011.5.25 are open) describe the preparation of 5-benzyl-4-alkyl-2-virtue aminothiazole hydrobromate.(CN102964312A, 2013.3.13 are open for Chinese invention patent; CN102924400A, 2013.2.13 are open; CN102936229A; 2013.2.20 open) describe
nthe preparation of-(the 4-tertiary butyl-5-benzyl thiazol-2-yl) acid amides and biological activity thereof.
Summary of the invention
The object of the present invention is to provide
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides (
i) or its salt;
I
In formula, R is selected from: C
1~ C
2alkyl, C
3~ C
4straight chain or C
3~ C
4branched-chain alkyl; Y
1, Y
3be selected from: hydrogen, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine or iodine; Y
2, Y
4be selected from: hydrogen, methyl, ethyl; N is selected from: 1,2,3,4,5,6 or 7; Z is selected from: hydrogen, methyl or phenyl; Salt is selected from: hydrochloride, hydrobromate, vitriol, phosphoric acid salt, mesylate, benzene sulfonate, tosilate.
The object of the present invention is to provide
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides is selected from following compounds:
。
The object of the present invention is to provide
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides and salt thereof the anti-human lung adenocarcinoma cell of preparation (
a549cell) or human breast cancer cell (
mCF-7cell) application in medicine.
The present invention compared with prior art tool has the following advantages:
The present invention is prepared first
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides and salt thereof, and find
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides or its salt have anti-human lung adenocarcinoma cell (
a549cell) or human breast cancer cell (
mCF-7cell) active.
Embodiment
Following examples are intended to the present invention instead of limitation of the invention further are described.
Embodiment 1
nthe preparation of-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) acrylamide
The 1 mmol 4-tertiary butyl-5-(4-chlorobenzyl) thiazole-2-amine and 20 mL methylene dichloride, ice bath stirs, and adds 0.5 mL triethylamine, and drip the 1.2 mmol acrylate chlorides be dissolved in 2 mL methylene dichloride, TLC monitors reaction, reacts 1.0 h.Revolve steaming solvent, dry method loading, column chromatography for separation obtains yellow solid
n-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) acrylamide, yield 83.2%, m.p. 128 ~ 130 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：8.93（s，1H，CONH），7.26（d，
J = 8.4 Hz，2H，C
6H
4），7.12（d，
J = 8.4 Hz，2H，C
6H
4），6.50（d，
J = 16.8 Hz，1H，COCH），6.19（dd，
J = 16.8 Hz，
J = 10.4 Hz，1H，=CH
2），5.87（d，
J = 10.4 Hz，1H，=CH
2），4.21（s，2H，CH
2），1.35（s，9H，3×CH
3）。
Embodiment 2
nthe preparation of-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) crotonamide
(1) preparation of crotonyl chloride
19.9 mmol β-crotonic acids and 15 mL thionyl chlorides, stir, and 60 DEG C of reaction 5.0 h, revolve the thionyl chloride of steamed amount, obtain orange-yellow liquid crotonyl chloride, put into Refrigerator store for subsequent use.
(2)
nthe preparation of-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) crotonamide
According to the preparation method of embodiment 1, react 1.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) crotonamide, yield 67.4%, m.p. 135 ~ 136 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：8.91（s，1H，CONH），7.25（d，
J = 8.4 Hz，2H，C
6H
4），7.12（d，
J = 8.4 Hz，2H，C
6H
4），5.92（dd，
J = 12.0 Hz，1H，COCH），4.20（s，2H，CH
2），2.79（dd，
J = 12.0 Hz，1H，C=CH），1.93（dd，
J = 6.8 Hz，2H，CH
3），1.61（d，
J = 6.8 Hz，1H，CH
3），1.35（s，9H，3×CH
3）。
Embodiment 3
nthe preparation of-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) sorb acid amides
The 1 mmol 4-tertiary butyl-5-(4-chlorobenzyl) thiazole-2-amine and 20 mL methylene dichloride, stir, add 0.16 mmol DMAP and 1.2 mmol Sorbic Acids, stir 0.5 h, add 1.2 mmol DCC, TLC monitors reaction, reacts 3.0 h; Revolve steaming solvent, dry method loading, column chromatography for separation obtains yellow solid
n-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) sorb acid amides, yield 91.1%, m.p. 185 ~ 186 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：7.38~7.32（m，1H，COCH=CH），7.25（d，2H，
J = 8.4 Hz，C
6H
4），7.09（d，2H，
J = 8.4 Hz，C
6H
4），6.21~6.19（m，2H，
J = 4.4 Hz，CH=CH），5.82（d，1H，COCH），4.20（s，2H，CH
2），1.87（d，1H，
J = 4.4 Hz，CH
3），1.34（s，9H，3×CH
3）。
Embodiment 4
nthe preparation of-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) cinnamide
According to the preparation method of embodiment 1, react 1.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(4-chlorobenzyl) thiazol-2-yl) cinnamide, yield 67.1%, m.p. 163 ~ 165 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：7.80（d，1H，
J = 15.6 Hz，C
6H
5CH），7.53（dd，2H，
J = 5.6 Hz，
J = 2.0 Hz，C
6H
52-H，6-H），7.40（t，3H，
J = 5.6 Hz，
J = 2.0 Hz，C
6H
53-H，4-H，5-H），7.27（d，2H，
J = 8.4 Hz，C
6H
4），7.14（d，2H，
J = 8.4 Hz，C
6H
4），6.50（d，1H，
J = 15.6 Hz，COCH），4.25（s，2H，CH
2），1.37（s，9H，3×CH
3）。
Embodiment 5
n-the preparation of (the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) acrylamide
The 1 mmol 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazole-2-amine and 20 mL methylene dichloride, ice bath stirs, and adds 0.5 mL triethylamine, and drip the 1.2 mmol acyl chlorides be dissolved in 2 mL methylene dichloride, TLC monitors reaction, reacts 1.0 h.Revolve steaming solvent, dry method loading, column chromatography for separation obtains yellow solid
n-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) acrylamide, yield 78.2%, m.p. 144 ~ 145 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：8.96（s，1H，CONH），7.39（d，
J = 2.0 Hz，1H，C
6H
33-H），7.16（dd，
J = 8.4 Hz，
J = 2.0 Hz，1H，C
6H
35-H），7.04（d，
J = 8.4 Hz，1H，C
6H
36-H），6.50（d，
J = 16.8 Hz，1H，COCH），6.22（dd，
J = 16.8 Hz，
J = 10.4 Hz，1H，=CH
2），5.87（d，
J = 10.4 Hz，1H，=CH
2），4.27（s，2H，CH
2），1.34（s，9H，3×CH
3）。
Embodiment 6
nthe preparation of-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) crotonamide
According to the preparation method of embodiment 1, react 2.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) crotonamide, yield 58.1%, m.p. 172 ~ 173 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：8.85（s，1H，CONH），7.39（d，1H，
J = 2.0 Hz，C
6H
33-H），7.16（dd，1H，
J = 8.4 Hz，
J = 2.0 Hz，C
6H
35-H），7.10（dd，1H，
J = 15.2 Hz，CH
3 CHCH），7.04（d，1H，
J = 8.4 Hz，C
6H
36-H），5.92（dd，1H，
J = 15.2 Hz，
J = 1.6 Hz，CO
CHCH），4.26（s，2H，CH
2），1.93（dd，3H，
J = 1.6 Hz，CH
3），1.34（s，9H，3×CH
3）。
Embodiment 7
nthe preparation of-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) sorb acid amides
According to the preparation method of embodiment 3, react 3.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) sorb acid amides, yield 85.7%, m.p. 165 ~ 166 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：7.39（d，1H，
J = 2.0 Hz，C
6H
33-H），7.38~7.33（m，1H，COCH=CH），7.16（dd，1H，
J = 8.4 Hz，
J = 2.0 Hz，C
6H
35-H），7.04（d，1H，
J = 8.4 Hz，C
6H
36-H），6.22~6.20（m，2H，
J = 4.4 Hz，CH=CH），5.84（d，1H，COCH），4.26（s，2H，CH
2），1.87（d，1H，
J = 4.4 Hz，CH
3），1.34（s，9H，3×CH
3）。
Embodiment 8
nthe preparation of-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) cinnamide
According to the preparation method of embodiment 1, react 1.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) cinnamide, yield 54.5%, m.p. 173 ~ 174 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：9.20（s，1H，CONH），7.82~7.05（m，9H，C
6H
3，C
6H
5，C
6H
5CH），6.51（d，1H，COCH），4.28（s，2H，CH
2），1.35（s，9H，3×CH
3）。
Embodiment 9
nthe preparation of-(the 4-tertiary butyl-5-(4-methoxy-benzyl) thiazol-2-yl) acrylamide
According to the preparation method of embodiment 1, react 2.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(4-methoxy-benzyl) thiazol-2-yl) acrylamide, yield 86.6%, m.p. 147 ~ 148 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：7.11（d，2H，
J = 8.4 Hz，C
6H
4），6.81（d，2H，
J = 8.4 Hz，C
6H
4），6.48（d，1H，
J = 15.8 Hz，CH=），6.21（dd，1H，
J = 15.8 Hz，
J = 10.4 Hz，=CH
2），5.82（dd，1H，
J = 10.4 Hz，
J = 4.4 Hz，=CH
2），4.18（s，2H，CH
2），3.79（s，1H，OCH
3），1.36（s，9H，3×CH
3）。
Embodiment 10
nthe preparation of-(the 4-tertiary butyl-5-(4-methoxy-benzyl) thiazol-2-yl) crotonamide
According to the preparation method of embodiment 1, react 2.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(4-methoxy-benzyl) thiazol-2-yl) crotonamide, yield 77.1%, m.p. 180 ~ 182 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：8.95（s，1H，CONH），7.11（d，2H，
J = 8.4 Hz，C
6H
4），7.05（dd，1H，
J = 15.2 Hz，
J = 6.8 Hz，COCH），6.82（d，2H，
J = 8.4 Hz，C
6H
4），5.91（dd，1H，
J = 15.2 Hz，
J = 2.0 Hz，CH），4.17（s，2H，CH
2），3.77（s，3H，OCH
3），1.92（dd，3H，
J = 6.8 Hz，
J = 2.0 Hz，CH
3），1.37（s，9H，3×CH
3）。
Embodiment 11
nthe preparation of-(the 4-tertiary butyl-5-(4-methoxy-benzyl) thiazol-2-yl) cinnamide
According to the preparation method of embodiment 1, react 2.0 h, obtain yellow solid
n-(the 4-tertiary butyl-5-(4-methoxy-benzyl) thiazol-2-yl) cinnamide, yield 75.6%, m.p. 152 ~ 153 DEG C.
1H NMR（400 MHz，CDCl
3）
δ：7.70（d，1H，
J = 15.6 Hz，CH），7.45（dd，2H，C
6H
5 2-H，6-H），7.32（t，3H，C
6H
53-H，4-H，5-H），7.06（d，2H，
J = 8.4 Hz，C
6H
4），6.77（d，2H，
J = 8.4 Hz，C
6H
4），6.41（d，1H，
J = 15.6 Hz，COCH），4.12（s，2H，CH
2），3.72（s，3H，OCH
3），1.31（s，9H，3×CH
3）。
Embodiment 12
nthe anti-tumor activity of-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides and salt thereof
1. anti-tumor activity principle
Mtt assay biological activity test, also known as MTT colorimetry, is a kind of method detecting cell survival and growth.MTT analytical method with living cells metabolize thing reductive agent tetrazolium bromide [3-(4,5-dimethyl-2-thiazole)-2,5-phenylbenzene bromination tetrazoles; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT] based on.MTT is a kind of dyestuff that can accept hydrogen atom.The MTT of yellow can be changed into insoluble hepatic first a ceremonial jade-ladle, used in libation (formazon) by desaturase relevant to NADP in viable cell plastosome in cell, and dead cell is then without this function.After dissolving formazon with DMSO, under certain wavelength, measure optical density value by microplate reader, both quantitatively can measure the survival rate of cell.Sample is observed to the restraining effect of tumour cell according to the change of optical density value.
2. anti-tumor activity experiment
Sample:
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides (
i) and salt:
I
In formula, R is selected from: C
1~ C
2alkyl, C
3~ C
4straight chain or C
3~ C
4branched-chain alkyl; Y
1, Y
3be selected from: hydrogen, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine or iodine; Y
2, Y
4be selected from: hydrogen, methyl, ethyl; N is selected from: 1,2,3,4,5,6 or 7; Z is selected from: hydrogen, methyl or phenyl.
Clone: lung adenocarcinoma cell system
a549and breast cancer cell line
mCF-7(Xiangya Medical College, Zhongnan Univ cell bank provides).
Reagent: tetrazolium bromide (MTT), RPMI RPMI-1640, new-born calf serum, microbiotic (hero Life Technologies, Inc. of the U.S.); Pancreatin (AMRESCO company of the U.S.); 96 well culture plates (hero Life Technologies, Inc. of the U.S.); Dimethyl sulfoxide (DMSO) (Sigma Co., USA).
Instrument: HFsafe-1500 type Bechtop, HF151UV type CO
2incubator (Shanghai Lishen Scientific Equipment Co., Ltd.); XSP-15C type inverted microscope (the rectangular opticinstrument company limited in Shanghai); Multiskan MK3 type microplate reader (Thermo company of the U.S.); Ultrapure water preparing instrument (Milli-Q company of the U.S.).
Experimental implementation: sample pair
a549cell and
mCF-7the test of cell.The experimental implementation process of often kind of cell is identical, in an experimentation, per sample (p.s.) arranges 5 concentration gradients (0.010 μm of ol/mL, 0.030 μm of ol/mL, 0.100 μm of ol/mL, 0.300 μm of ol/mL and 1.000 μm ol/mL), each concentration four parallel samples, often parallel 3 times of group experiment, and reached a conclusion by the contrast of blank group.Microplate reader detects each hole OD value, determined wavelength 570 nm.
3. antitumor activity evaluation
1) cell inhibitory rate calculates:
2) IC
50value calculates
Sample solution concentration logarithmic value and cell inhibitory rate linear regression, utilize computed in software sample to the half-inhibition concentration IC of cell
50value.
n-(the 4-tertiary butyl-5-(2,4-dichloro benzyl) thiazol-2-yl) acrylamide to human lung adenocarcinoma cell (
a549cell) and human breast cancer cell (
mCF-7cell) IC
50be respectively 64.0 μm of ol/L and 52.0 μm ol/L.
Active testing result shows,
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides or its salt pair human lung adenocarcinoma cell (
a549cell) and human breast cancer cell (
mCF-7cell) there is good inhibit activities, can be used for preparing antitumor drug.
Claims (3)
1. chemical structural formula
ishown
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides or its salt;
I
In formula, R is selected from: C
1~ C
2alkyl, C
3~ C
4straight chain or C
3~ C
4branched-chain alkyl; Y
1, Y
3be selected from: hydrogen, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine or iodine; Y
2, Y
4be selected from: hydrogen, methyl, ethyl; N is selected from: 1,2,3,4,5,6 or 7; Z is selected from: hydrogen, methyl or phenyl; Salt is selected from: hydrochloride, hydrobromate, vitriol, phosphoric acid salt, mesylate, benzene sulfonate, tosilate.
2. according to claim 1
n-(4-alkyl-5-benzyl thiazol-2-yl) alkene acid amides is selected from following compounds:
。
3. described in claim 1 or 2
n-(4-alkyl-5-benzyl thiazol-2-yl) application of alkene acid amides in the anti-human lung adenocarcinoma cell of preparation or human breast cancer cell medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510406074.XA CN105017174B (en) | 2015-07-13 | 2015-07-13 | N‑（4 alkyl, 5 benzyl thiazole, 2 base）Acrylamide and preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510406074.XA CN105017174B (en) | 2015-07-13 | 2015-07-13 | N‑（4 alkyl, 5 benzyl thiazole, 2 base）Acrylamide and preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105017174A true CN105017174A (en) | 2015-11-04 |
| CN105017174B CN105017174B (en) | 2017-03-15 |
Family
ID=54407525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510406074.XA Expired - Fee Related CN105017174B (en) | 2015-07-13 | 2015-07-13 | N‑（4 alkyl, 5 benzyl thiazole, 2 base）Acrylamide and preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105017174B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105541827A (en) * | 2016-02-16 | 2016-05-04 | 湖南大学 | Benzylhydrazonothiazolylmethylquinolinone derivatives, and application thereof as anticancer drugs |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1325389A (en) * | 1998-10-30 | 2001-12-05 | 法玛西雅厄普约翰公司 | 2-amino-thiazole derivatives, process for their preparation, and their use as antitumor agents |
| WO2002050071A1 (en) * | 2000-12-21 | 2002-06-27 | Bristol-Myers Squibb Company | Thiazolyl inhibitors of tec family tyrosine kinases |
| TW201300359A (en) * | 2010-12-29 | 2013-01-01 | Dev Center Biotechnology | Novel tubulin inhibitors |
| CN102964312A (en) * | 2012-12-03 | 2013-03-13 | 湖南大学 | 4-tertiary butyl-5-(1-aryl-2-nitre ethyl)-2-acylamino thiazole 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 |
-
2015
- 2015-07-13 CN CN201510406074.XA patent/CN105017174B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1325389A (en) * | 1998-10-30 | 2001-12-05 | 法玛西雅厄普约翰公司 | 2-amino-thiazole derivatives, process for their preparation, and their use as antitumor agents |
| WO2002050071A1 (en) * | 2000-12-21 | 2002-06-27 | Bristol-Myers Squibb Company | Thiazolyl inhibitors of tec family tyrosine kinases |
| TW201300359A (en) * | 2010-12-29 | 2013-01-01 | Dev Center Biotechnology | Novel tubulin inhibitors |
| CN102964312A (en) * | 2012-12-03 | 2013-03-13 | 湖南大学 | 4-tertiary butyl-5-(1-aryl-2-nitre ethyl)-2-acylamino thiazole 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 |
Non-Patent Citations (1)
| Title |
|---|
| 彭俊梅等: "5 -苄基-4-叔丁基-2 -芳氨基噻唑氢溴酸盐的合成 表征及抗肿瘤活性", 《高等学校化学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105541827A (en) * | 2016-02-16 | 2016-05-04 | 湖南大学 | Benzylhydrazonothiazolylmethylquinolinone derivatives, and application thereof as anticancer drugs |
| CN105541827B (en) * | 2016-02-16 | 2018-01-19 | 湖南大学 | Benzyl hydrazono- benzothiazolylmethyl qualone derivative and its application as anticarcinogen |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105017174B (en) | 2017-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103333132B (en) | N-(4-tertbutyl-5-benzyl thiazole-2-yl)amide and preparation method and application thereof | |
| CN103664927B (en) | N-[5-(1,2,4-triazole-1-yl)thiazole-2-yl]aryl amide, preparation method, and applications thereof | |
| CN101845026A (en) | 5-(4-chlorophenylmethyl)-4-tertiary butyl thiazole derivatives and preparation method and application thereof | |
| CN103086921B (en) | 2-(4-aryloxyphenoxy)alkylamide and application thereof | |
| CN105017174A (en) | N- (4-alkyl-5-benzyl thiazole-2-base) enoyl-amine and preparation method and application thereof | |
| CN106317050B (en) | A kind of phenyl thiazole derivant and the preparation method and application thereof | |
| CN103467368B (en) | Medical application of N-pyridine methyl/ methoxyl-2-phenoxyl amide | |
| CN103086985A (en) | 2-[4-(quinoxaline-2-oxygroup) phenoxy] alkylamide and application thereof | |
| CN103159674A (en) | 2-benzene alkyl amid compound and preparation method, medical composition and use thereof | |
| CN103086995B (en) | 2-[4-(benzoxazole-2-oxygroup) phenoxy] alkylamide and application thereof | |
| CN103450181B (en) | Medical application of 2-[4-(quinoxaline-2-oxy)phenoxy]amide | |
| CN105078977A (en) | Application of 5-(2-nitro ethyl) thiazole derivatives as anticancer drug | |
| CN105055405A (en) | Application of N-(4-alkyl-5-benzyl thiazole-2-yl) haloalkane amide as anti-cancer drug | |
| CN106467498A (en) | N-（Thiazol-2-yl）Aminoamide derivatives and preparation method and application | |
| CN102942535B (en) | 4-tertiary butyl-5-(2-nitroxyethyl)-2-aminothiazole, as well as preparation method and application thereof | |
| CN103601697B (en) | 4-tertiary butyl-5-(2-nitroethyl)-2-acylamino thiazole and preparation method and application thereof | |
| CN105085480B (en) | 2‑[4‑（The epoxide of quinoxaline 2）Phenoxy group] fatty acyl pyridine amine medical usage | |
| CN103497183B (en) | Medical application of N-thiazolmethyl/methoxy-2-phenoxyamide | |
| CN102070565A (en) | 4-alkyl-6-aryl-5-acetyl-1, 3-thiazine, and preparation method and application thereof | |
| CN105085506B (en) | The medical usage of 2 [epoxide of 4 (benzoxazoles 2) phenoxy group] fatty acyl pyridine amine | |
| CN105085385B (en) | The medical usage of 2 [4 (epoxide of pyridine 2) phenoxy group] fatty acyl pyridine amine | |
| CN104327055A (en) | 1-(benzofuran-5-yl)-2-(1, 2, 4-triazole-1-yl)ketoxime ether amide, preparation method and application thereof | |
| CN103450180A (en) | Medical application of 2-[4-(benzoxazole-2-oxy)phenoxy]amide | |
| CN106699682A (en) | N-(4-alkyl-5-benzylthiazol-2-yl)aminoalkylamide, and preparation method and application thereof | |
| CN102702113A (en) | 5-Fluorouracil derivative and preparation method and uses |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| 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: 20170315 Termination date: 20170713 |