CN105017351B - A kind of glycosyl pyrazole compound and its preparation and application - Google Patents
A kind of glycosyl pyrazole compound and its preparation and application Download PDFInfo
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- CN105017351B CN105017351B CN201410159468.5A CN201410159468A CN105017351B CN 105017351 B CN105017351 B CN 105017351B CN 201410159468 A CN201410159468 A CN 201410159468A CN 105017351 B CN105017351 B CN 105017351B
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- pyrazole compound
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Abstract
The invention discloses a kind of glycosyl pyrazole compound and its preparation and application, the structure such as formula of the glycosyl pyrazole compound（I）It is shown.The preparation method of the glycosyl pyrazole compound includes：Formula（II）4 shown glucopyranose benzoyl hydrazines and formula（III）Shown cyclohexadione compounds are reacted in aqueous solvent under the conditions of Microwave-assisted firing, production（I）Shown glycosyl pyrazole compound.Glycosyl pyrazole compound of the present invention has good anti-lung neoplasm activity, available for preparing anti-lung neoplasm medicine.
Description
（One）Technical field
The present invention relates to a kind of glycosyl pyrazole compound and its preparation method and application, especially anti-lung neoplasm is being prepared
Application in medicine.
（Two）Background technology
The preferable physiologically active that pyrazole compound is shown by it, especially preferably should what anti-tumor aspect was shown
With prospect, the favor of more and more antineoplastic researchers has been obtained.Although pyrazole compound has preferably antitumor
Activity, but exist intracellular toxic side effect it is larger, it is water-soluble bad the shortcomings of.And glycosyl modifiedization quickly grown in recent years
The research of compound can be very good to solve this difficulty.Research shows that not only bioactivity has by glycosyl modified compound
Improved, water solubility is also improved.Therefore, glycosyl pyrazole compound antitumor activity is meaningful.The present invention
It is that in this context, the antitumor activity of the glycosyl pyrazole compound of synthesis is studied.
（Three）The content of the invention
It is an object of the invention to provide a kind of glycosyl pyrazole compound with preferably anti-lung neoplasm activity and its preparation
Methods and applications.
For achieving the above object, the present invention is adopted the following technical scheme that：
The invention provides a kind of glycosyl pyrazole compound, its structure such as formula（I）It is shown：
Formula（I）In, R1Selected from one of following：C1~C5Alkyl;R2Selected from one of following：Hydrogen, C1~C5Alkyl, halogen
Element.
Further, described glycosyl pyrazole compound is one of following：
Present invention also offers a kind of formula（I）The preparation method of shown glycosyl pyrazole compound, including：Formula（II）Institute
The 4- glucopyranoses benzoyl hydrazine and formula shown（III）Shown cyclohexadione compounds are in aqueous solvent in Microwave-assisted firing bar
Reacted under part, production（I）Shown glycosyl pyrazole compound；
Formula（III）In, R1And R2The same formula of definition（I）.
Further, microwave power is 450W, and keeping temperature is 95~100 DEG C, 10~15min of reaction time.
Glycosyl pyrazole compound of the present invention has preferably anti-lung neoplasm (especially lung cancer) activity, can be used for
Prepare anti-lung neoplasm medicine.
Compared with prior art, the beneficial effects of the present invention are：The invention provides one kind there is preferable anti-lung to swell
The glycosyl pyrazole compound of tumor activity.
（Four）Embodiment
Technical scheme is described further with specific embodiment below, but protection scope of the present invention is not limited
In this：
Embodiment 1：
1. by formula（II）Shown 4- glucopyranose benzoyl hydrazine 314mg and acetylacetone,2,4-pentanedione 2mL is added to 30mL distillations
In water, microwave power is maintained at 450W, and it is 100 DEG C to keep maximum temperature, and the reaction time is 10min.After completion of the reaction, it is spin-dried for molten
Agent water, crude product is separated with silica gel column chromatography method, and solvent is ethyl acetate：Petroleum ether（Volume ratio）=4:1, obtain glycosyl
Pyrazole compound such as formula（I-1）332mg, yield is 88%.
Solid;M.p.105-107℃;IR(KBr,cm-1)vmax3362,2924,1693,1605,1509,1418,1350,
1244,1076;MS(ESI):M/z (%) 379.1489 [M+H]+；1H NMR(500MHz,DMSO):δ=7.93(d,J=8.8Hz,
2H,ArH),7.14(d,J=8.7Hz,2H,ArH),6.27(s,1H,Pyr-H),5.43(d,J=4.2Hz,1H,GH),5.17(d,
J=3.4Hz,1H,GH),5.10(d,J=5.1Hz,1H,GH),5.03(t,J=9.7Hz,1H,GH),4.62(t,J=5.6Hz,1H,
GH),3.71(dd,J=10.9,4.6Hz,1H,GH),3.51-3.48(m,1H,GH),3.45-3.40(m,4H,OH),2.54(s,
3H,CH3),2.17(s,3H,CH3);13C NMR(126MHz,DMSO):δ=167.32,161.13,151.75,144.86,
133.75,126.55,115.75,111.49,100.32,77.59,77.00,73.60,70.02,61.05,14.37,13.97.
2. inhibiting rate data determination
Bed board is non-small cell lung cancer cell strain A-549, totally 96 orifice plate, 8000/hole, dosing, and dilution drug concentration is
10-4mol/L.It is incubated mtt assay after 24h and determines absorbance at 490nm.Inhibition rate of tumor cell is calculated as the following formula：Suppress
Each administration group/blank controls of rate %=1-.Experimental group OD values are 0.2235, and blank group OD values are 0.2995, to non-small cell lung cancer
Cell line A-549 inhibiting rate is 25.38%.
3.IC50Value is determined
Bed board is non-small cell tumor cell line A-549, totally 96 orifice plate, 8000/hole, dosing, respectively by administration concentration
It is diluted to 10-5mol/L、10-6mol/L、10-7mol/L、10-8mol/L.Various kinds of drug is incubated mtt assay after 24h and determined at 490nm
Absorbance, calculates inhibition rate of tumor cell, and calculate compound to non-small cell lung cancer cell strain A-549 with Bliss methods
IC50It is worth for 5.43 μM.
Embodiment 2：
1. it is same as Example 1 to change acetylacetone,2,4-pentanedione 2mL into 3- chloracetyl acetone 2.5mL other conditions.Obtain glycosyl pyrrole
Azole compounds such as formula（I-2）330mg, yield is 80%.
Solid;M.p.115-117℃;IR(KBr,cm-1)vmax3373,2925,1699,1605,1507,1417,1343,
1247,1076;MS(ESI):M/z (%) 451.0662 [M+K]+;1H NMR(500MHz,DMSO):δ=7.91(d,J=8.7Hz,
2H Ar-H),7.16(d,J=8.7Hz,2H,Ar-H),5.37(s,1H,GH),5.06-5.01(m,3H,GH),4.56(s,1H,
GH),3.72(d,J=11.4Hz,1H,GH),3.49(dd,J=11.5,5.4Hz,1H,GH),3.31(d,J=6.7Hz,4H),
2.55(s,3H,CH3),2.21(s,3H,CH3);13C NMR(126MHz,DMSO):δ=166.93,161.45,148.70,
140.40,133.90,125.61,115.90,113.74,100.36,77.63,77.02,73.62,70.07,61.09,
12.39,11.86.
2. inhibiting rate data determination
I-1 is changed into I-2, other conditions are same as Example 1, experimental group OD values are 0.2654, blank group OD values are
0.2995, the inhibiting rate to non-small cell lung cancer cell strain A-549 is 11.38%.
3.IC50Value is determined
I-1 is changed into I-2, other are same as Example 1, to non-small cell lung cancer cell strain A-549 IC50It is worth and is
30.36μM。
Embodiment 3：
1. it is same as Example 1 to change acetylacetone,2,4-pentanedione 2mL into 3,5- heptadione 2.5mL other conditions.Obtain glycosyl pyrazoles
Class compound such as formula（I-3）349mg, yield is 86%.
Solid;M.p.125-128℃;IR(KBr,cm-1)vmax3330,2969,1694,1604,1506,1417,1359,
1248,1066;MS(ESI):M/z (%) 407.1812 [M+H]+；1H NMR(500MHz,DMSO):δ=7.93(d,J=8.8Hz,
2H,Ar-H),7.15(d,J=8.8Hz,2H,Ar-H),6.35(s,1H,Pyr-H),5.44(d,J=3.6Hz,1H,GH),5.18
(s,1H,GH),5.10(d,J=4.9Hz,1H,GH),5.05(d,J=7.0Hz,1H,GH),4.62(t,J=5.2Hz,1H,GH),
3.72(dd,J=10.9,4.4Hz,1H,GH),3.52-3.49(m,1H,GH),3.46–3.36(m,4H,OH),2.98(q,J=
7.3Hz,2H,CH2),2.55(q,J=7.6Hz,2H,CH2),1.23(t,J=7.3Hz,3H,CH3),1.17(t,J=7.6Hz,3H,
CH3).13C NMR(126MHz,DMSO):δ=167.39,161.12,157.25,151.07,133.80,126.67,115.73,
108.31,100.28,77.57,76.99,73.61,70.02,61.05,21.49,13.40,13.20.
2. inhibiting rate data determination
I-1 is changed into I-3, other conditions are same as Example 1, experimental group OD values are 0.2174, blank group OD values are
0.2995, the inhibiting rate to non-small cell lung cancer cell strain A-549 is 27.41%.
3.IC50Value is determined
I-1 is changed into I-3, other data are same as Example 1, to non-small cell lung cancer cell strain A-549 IC50It is worth and is
3.15μM。
Claims (5)
1. a kind of glycosyl pyrazole compound, its structure such as formula（I）It is shown：
Formula（I）In, R1Selected from one of following：C1~C5Alkyl;R2Selected from one of following：Hydrogen, C1~C5Alkyl, halogen.
2. glycosyl pyrazole compound as claimed in claim 1, it is characterised in that the glycosyl pyrazole compound is following
One of：
3. a kind of preparation method of glycosyl pyrazole compound as claimed in claim 1, including：Formula（II）Shown 4- pyrans
Glucose benzoyl hydrazine and formula（III）Shown cyclohexadione compounds are carried out instead in aqueous solvent under the conditions of Microwave-assisted firing
Should, production（I）Shown glycosyl pyrazole compound；
Formula（III）In, R1And R2The same formula of definition（I）.
4. the preparation method of glycosyl pyrazole compound as claimed in claim 3, it is characterised in that：Microwave power is 450W,
Keeping temperature is 95~100 DEG C, 10~15min of reaction time.
5. application of the glycosyl pyrazole compound as claimed in claim 1 in anti-lung neoplasm medicine is prepared.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101180306A (en) * | 2005-03-17 | 2008-05-14 | 橘生药品工业株式会社 | Process for production of glucopyranosyloxypyrazole derivative |
| CN101307078A (en) * | 2008-01-03 | 2008-11-19 | 青岛科技大学 | Galactosyl thiourea heterocyclic compounds, synthetic method thereof and antineoplastic applications |
| CN103649033A (en) * | 2011-05-26 | 2014-03-19 | Tf化学公司 | Family of aryl, heteroaryl, O-aryl and O-heteroaryl carbasugars |
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2014
- 2014-04-18 CN CN201410159468.5A patent/CN105017351B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101180306A (en) * | 2005-03-17 | 2008-05-14 | 橘生药品工业株式会社 | Process for production of glucopyranosyloxypyrazole derivative |
| CN101307078A (en) * | 2008-01-03 | 2008-11-19 | 青岛科技大学 | Galactosyl thiourea heterocyclic compounds, synthetic method thereof and antineoplastic applications |
| CN103649033A (en) * | 2011-05-26 | 2014-03-19 | Tf化学公司 | Family of aryl, heteroaryl, O-aryl and O-heteroaryl carbasugars |
Non-Patent Citations (3)
| Title |
|---|
| "Convenient synthesis and antimicrobial evaluation of some novel 2-substituted-3-methylbenzofuran derivatives";Hatem A. Abdel-Aziz et al.;《European Journal of Medicinal Chemistry》;20090227;第44卷;第3637-3644页 * |
| "Synthesis and antiproliferative activity of helonioside A, 3,4,6-tri-O-feruloylsucrose,lapathoside C and their analogs";Parthasarathi Panda et al.;《European Journal of Medicinal Chemistry》;20121027;第58卷;第418-430页 * |
| "Synthesis and antitumor activity of lapathoside D and its analogs";Parthasarathi Panda et al.;《European Journal of Medicinal Chemistry》;20120328;第53卷;第1-12页 * |
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