CN105237521A - Coumarin-isatin type compounds, and preparation method and purpose thereof - Google Patents
Coumarin-isatin type compounds, and preparation method and purpose thereof Download PDFInfo
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- CN105237521A CN105237521A CN201510702207.8A CN201510702207A CN105237521A CN 105237521 A CN105237521 A CN 105237521A CN 201510702207 A CN201510702207 A CN 201510702207A CN 105237521 A CN105237521 A CN 105237521A
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- 0 C[C@](CCC*)C=CCC=CCClCC1([*+]N)CC1 Chemical compound C[C@](CCC*)C=CCC=CCClCC1([*+]N)CC1 0.000 description 4
- LCBXNGGXXQBAAL-ZZXKWVIFSA-N C/C(/I)=C\CCNCI Chemical compound C/C(/I)=C\CCNCI LCBXNGGXXQBAAL-ZZXKWVIFSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention discloses a kind of coumarin-isatin type compounds, and a preparation method and a purpose thereof. The compounds possess a structure shown as a formula (I). The preparation method comprises taking 7-hydroxycoumarin and ethyl bromoacetate as raw materials to obtain [(2-oxo-2H-chromen-7-yl)oxy]acetic acid, and then performing hydrazinolysis reaction to obtain [(2-oxo-2H-chromen-7-yl)oxy]acetohydrazide, and finally reacting with various substituted isatins to obtain the corresponding target compounds. The compounds can be used as a raw material of an anti-diabetes medicament, and the preparation method is simple and easily-available in raw material and convenient to operate.
Description
Technical field
The present invention relates to a class tonka bean camphor-isatin type compound and preparation method thereof and as the application of alpha-glucosidase inhibitor in antidiabetic medicine.
Background technology
Diabetes are diseases of a kind of serious threat human life health.Along with improving constantly of living standards of the people, the sickness rate of global diabetes also presents the trend risen year by year always.Diabetes are a kind of decompensated diseases, and Etiological is that hypoinsulinism or islet function damage cannot excreting insulins, the metabolism syndrome being main biochemical feature with the hyperglycemia continued.The hyperglycemia continued also be cause its, kidney, nerve, the multiple systems generation pathology such as cardiovascular major cause, the hyperglycemia therefore controlling patient is of great significance the complication tool that treatment diabetes and prevent diabetes cause.Alpha-glucosidase is a kind of enzyme be present in human small intestine, and its physiological function is that the oligose in food is hydrolyzed into monose, thus is absorbed by the body.By the activity of Inhibiting α-glucosidase, the absorption of glucose in food can be hindered, play and reduce the effect of postprandial blood sugar, for I type and type ii diabetes patient all applicable.This class medicine such as acarbose, voglibose, miglitol etc. have been widely used in the clinical treatment of diabetes.But existing alpha-glucosidase inhibitor also exists active low, the shortcoming such as toxic side effect is larger, hinder its application clinically.Therefore, need to research and develop alpha-glucosidase inhibitor that is novel, efficient, low toxicity, to meet the needs for the treatment of diabetes.
Coumarin kind compound is the secondary metabolism product of a class plant, in various plants, have distribution.Many plants containing coumarin kind compound have had the history of several thousand as drug use in Asia.Coumarin kind compound has multiple biological activity, such as: anti-oxidant, anti-diabetic, antitumor, anti-inflammatory, anti-neurodegeneration, anti-malarial, anticoagulation, antibacterial and antimycotic etc.Due to chemical structure and the diversified biological activity of its uniqueness, coumarin kind compound has become design and has found the important lead compound source of new drug, develops it and has certain theory significance and actual value.
In addition isatin is a kind of endogenous active substance be present in mammalian tissues and body fluid.According to the literature, isatin and derivative thereof have multiple biological activity, as anti-diabetic, spasmolytic, tuberculosis, antibacterium, antimycotic, antiviral, antitumor etc.Therefore the research tool carrying out original new drug based on isatin is of great significance.Based on above analysis, tonka bean camphor structure, according to twin medicine principle, is connected with isatin structure by we, design and synthesis one class tonka bean camphor-isatin type compound.
Summary of the invention
Technical scheme of the present invention is as follows:
One class tonka bean camphor-isatin type compound, is characterized in that they have general structure as shown in the formula (I):
（I）
Wherein: R
1, R
2, R
3or R
4for hydrogen, halogen, alkyl, amino, alkylamino, alkoxyl group, cyano group, nitro, hydroxyl, trifluoromethyl or sulfydryl, R
1for hydrogen, alkyl, benzyl or substituted benzyl.
Prepare a method for above-mentioned tonka bean camphor-isatin type compound, it comprises the following steps:
Step 1: umbelliferone, ethyl bromoacetate, salt of wormwood are placed in round-bottomed flask, add acetone, back flow reaction 5 ~ 24 hours, stopped reaction, cool to room temperature, cross and filter salt of wormwood, filtrate is spin-dried for, and obtains white solid powder ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester with ethyl alcohol recrystallization; The mol ratio of described umbelliferone, ethyl bromoacetate, salt of wormwood is 1:(1 ~ 5): (1 ~ 4);
Step 2: ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester, hydrazine hydrate are placed in round-bottomed flask, add ethanol, back flow reaction 2 ~ 10, stopped reaction, cool to room temperature, filter, obtain 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide; Described ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester, the mol ratio of hydrazine hydrate are 1:(1 ~ 20);
Step 3: 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide, replacement isatin are placed in round-bottomed flask, add methyl alcohol and glacial acetic acid, back flow reaction 0.5 ~ 4 hour, cool to room temperature, there is solid to separate out, filter to obtain tonka bean camphor-isatin type compound (I); The mol ratio of described 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide, replacement isatin is 1:(1 ~ 5).
Tonka bean camphor of the present invention-isatin type compound has good inhibit activities to alpha-glucosidase, and the development and application for antidiabetic medicine provides new selection.
Accompanying drawing explanation
Fig. 1 is the syntheti c route figure of tonka bean camphor-isatin type compound.
Embodiment
Following embodiment is to describe the present invention in detail, and unrestricted the present invention.
Embodiment one: the preparation of ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester
By umbelliferone (1.62g, 10mmol), ethyl bromoacetate (1.84g, 11mmol), salt of wormwood (4.15g, 30mmol) be placed in round-bottomed flask, add acetone 100mL, back flow reaction 6 hours, TLC display reaction is complete, stopped reaction, cool to room temperature, cross and filter salt of wormwood, filtrate is spin-dried for, white solid powder is obtained, yield 86.4% with ethyl alcohol recrystallization.m.p.107-110
oC.。
The preparation of embodiment two: 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide
By ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester (2.48g, 10mmol), hydrazine hydrate (1.0g, 20mmol) be placed in round-bottomed flask, add 100mL ethanol, back flow reaction, TLC display reaction is complete, stopped reaction, cool to room temperature, filters, obtain white solid powder, yield 65.3%.m.p.171-175
oC。
Embodiment three: the preparation of (Z)-2-((2-oxo-2H-chromene-7-base) oxygen base)-N'-(2-oxindole alkane-3-subunit) acethydrazide (1)
By 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (234mg, 1mmol), isatin (147mg, 1mmol) be placed in round-bottomed flask, add 10mL methyl alcohol and a glacial acetic acid, back flow reaction 2 hours, stopped reaction, cool to room temperature, filter, obtain yellow solid powder, yield 87.4%.m.p.237-243
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.01(s,2H),6.32(d,1H,J=9.6Hz),6.94(d,1H,J=8.0Hz),7.05-7.10(m,3H),7.37(d,1H,J=8.4Hz),7.58-7.68(m,2H),8.00(d,1H,J=9.6Hz),10.23(s,1H),11.32(s,1H)。
Embodiment four: the preparation of (Z)-N'-(5-methyl-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (2)
Preparation method is with embodiment three, and just isatin replaces with 5-methylisatin, yield 81.3%.m.p.253-255
oC;
1HNMR(d
6-DMSO,400MHz)δ:2.30(s,3H),5.00(s,2H),6.32(d,1H,J=9.6Hz),6.83(d,1H,J=8.0Hz),7.05-7.10(m,2H),7.19(d,1H,J=8.0Hz),7.41(s,1H),7.69(s,1H),8.00(d,1H,J=9.6Hz),10.21(s,1H),11.18(s,1H).
Embodiment five: the preparation of (Z)-N'-(5,7-dimethyl-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (3)
Preparation method is with embodiment three, and just isatin replaces with 5,7-dimethylisatin, yield 75.5%.m.p.230-234
oC;
1HNMR(d
6-DMSO,400MHz)δ:2.21(s,3H),2.67(s,3H),5.02(s,2H),6.32(d,1H,J=9.6Hz),7.04-7.11(m,2H),7.21-7.28(m,2H),7.70(s,1H),8.01(d,1H,J=9.6Hz),10.22(s,1H),11.24(s,1H)。
Embodiment six: the preparation of (Z)-N'-(5-fluoro-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (4)
Preparation method is with embodiment three, and just isatin replaces with 5-fluoro indigo red, yield 79.3%.m.p.241-244
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.02(s,2H),6.33(d,1H,J=9.6Hz),6.94-6.97(m,1H),7.06(d,1H,J=8.8Hz),7.11(s,1H),7.22-7.27(m,1H),7.42(s,1H),7.69(s,1H),8.01(d,1H,J=9.6Hz),10.25(s,1H),11.31(s,1H)。
Embodiment seven: the preparation of (Z)-N'-(5-chloro-2-oxo indoles alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (5)
Preparation method is with embodiment three, and just isatin replaces with 5-chlorisatide, yield 89.1%.m.p.215-220
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.04(s,2H),6.30(d,1H,J=9.6Hz),6.35-6.38(m,2H),6.97-7.08(m,2H),7.43(dd,1H,J=2.4,8.8Hz),7.68(s,1H),8.01(d,1H,J=9.6Hz),10.23(s,1H),11.42(s,1H)。
Embodiment eight: the preparation of (Z)-N'-(5-bromo-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (6)
Preparation method is with embodiment three, and just isatin replaces with 5-bromoisatin, yield 69.2%.m.p.205-210
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.04(s,2H),6.34(d,1H,J=9.6Hz),6.91(d,1H,8.8Hz),7.06(d,1H,J=8.8Hz),7.12(d,1H,J=2.0Hz),7.56(dd,1H,J=2.0,8.8Hz),7.69-7.81(m,2H),8.02(d,1H,J=9.6Hz),10.24(s,1H),11.40(s,1H)。
Embodiment nine: the preparation of (Z)-N'-(5-nitro-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (7)
Preparation method is with embodiment three, and just isatin replaces with 5-Nitroisatoic, yield 77.9%.m.p.228-232
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.04(s,2H),6.32(d,1H,J=9.6Hz),7.08-7.17(m,3H),7.68-7.70(m,1H),8.00(d,1H,J=9.6Hz),8.30(dd,2H,J=2.0,8.8Hz),10.21(s,1H),11.91(s,1H)。
Embodiment ten: the preparation of (Z)-N'-(1-methyl-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (8)
Preparation method is with embodiment three, and just isatin replaces with 1-methylisatin, yield 68.3%.m.p.193-198
oC;
1HNMR(d
6-DMSO,400MHz)δ:3.23(s,3H),5.04(s,2H),6.33(d,1H,J=9.6Hz),7.01-7.18(m,3H),7.49-7.51(m,1H),7.62-7.73(m,2H),8.02(d,1H,J=9.6Hz),10.24(s,1H),11.40(s,1H)。
Embodiment 11: the preparation of (Z)-N'-(1-benzyl-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (9)
Preparation method is with embodiment three, and just isatin replaces with 1-benzyl isatin, yield 85.4%.m.p.246-249
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.03(s,2H),5.04(s,2H),6.34(d,1H,J=9.6Hz),7.08-7.19(m,3H),7.29-7.44(m,7H),7.68-7.71(m,2H),8.03(d,1H,J=9.6Hz),10.25(s,1H)。
Embodiment 12: the preparation of (Z)-N'-(1-(2-luorobenzyl)-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (10)
Preparation method is with embodiment three, and just isatin replaces with 1-(2-luorobenzyl) isatin, yield 87.9%.m.p.252-255
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.03(s,2H),5.04(s,2H),6.33(d,1H,J=9.6Hz),6.99-7.08(m,2H),7.12-7.19(m,3H),7.23-7.28(m,1H),7.36-7.45(m,3H),7.68-7.70(m,2H),8.02(d,1H,J=9.6Hz),10.25(s,1H)。
Embodiment 13: the preparation of (Z)-N'-(1-(3-luorobenzyl)-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (11)
Preparation method is with embodiment three, and just isatin replaces with 1-(3-luorobenzyl) isatin, yield 71.4%.m.p.248-250
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.03(s,2H),5.04(s,2H),6.33(d,1H,J=9.6Hz),7.05-7.19(m,5H),7.22(d,1H,J=8.8Hz),7.26(d,1H,J=8.8Hz),7.38-7.43(m,2H),7.68-7.73(m,2H),8.02(d,1H,J=9.6Hz),10.24(s,1H)。
Embodiment 14: the preparation of (Z)-N'-(1-(2-chlorobenzyl)-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (12)
Preparation method is with embodiment three, and just isatin replaces with 1-(2-chlorobenzyl) isatin, yield 82.0%.m.p.185-188
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.04(s,2H),5.06(s,2H),6.33(d,1H,J=9.6Hz),6.93(d,1H,J=8.0Hz),7.04(dd,1H,J=2.0,8.0Hz),7.18(t,1H,J=8.0Hz),7.24-7.40(m,5H),7.52(d,1H,J=8.8Hz),7.68-7.69(m,2H),8.02(d,1H,J=9.6Hz),10.22(s,1H)。
Embodiment 15: the preparation of (Z)-N'-(1-(4-bromobenzyl)-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (13)
Preparation method is with embodiment three, and just isatin replaces with 1-(4-bromobenzyl) isatin, yield 74.6%.m.p.254-260
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.00(s,2H),5.05(s,2H),6.33(d,1H,J=9.6Hz),7.05-7.19(m,4H),7.35(d,2H,J=8.0Hz),7.42(t,1H,J=8.0Hz),7.55(d,2H,J=8.0Hz),7.65-7.67(m,2H),8.02(d,1H,J=9.6Hz),10.23(s,1H)。
Embodiment 16: the preparation of (Z)-N'-(1-(2-luorobenzyl)-5-methyl-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (14)
Preparation method is with embodiment three, and just isatin replaces with 1-(4-bromobenzyl)-5-methylisatin, yield 73.9%.m.p.214-216
oC;
1HNMR(d
6-DMSO,400MHz)δ:2.32(s,3H),5.04(s,2H),5.05(s,2H),6.34(d,1H,J=9.6Hz),6.93(d,1H,J=8.0Hz),7.01(d,1H,J=8.8Hz),7.13(s,1H),7.18(t,1H,J=8.0Hz),7.23(d,1H,J=8.8Hz),7.26(d,1H,J=8.0Hz),7.34-7.38(m,2H),7.51(s,1H),7.66-7.72(m,1H),8.02(d,1H,J=9.6Hz),10.25(s,1H)。
Embodiment 17: the preparation of (Z)-N'-(1-(3-luorobenzyl)-5-methyl-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (15)
Preparation method is with embodiment three, and just isatin replaces with 1-(3-bromobenzyl)-5-methylisatin, yield 80.1%.m.p.215-217
oC;
1HNMR(d
6-DMSO,400MHz)δ:2.32(s,3H),5.02(s,2H),5.04(s,2H),6.34(d,1H,J=9.6Hz),6.37(dd,1H,J=2.4,8.8Hz),6.43(d,1H,J=2.4Hz),6.94(d,1H,J=8.0Hz),7.08-7.16(m,2H),7.20-7.28(m,2H),7.40(d,1H,J=8.0Hz),7.51(s,1H),7.66-7.72(m,1H),8.03(d,1H,J=9.6Hz),10.25(s,1H)。
Embodiment 18: the preparation of (Z)-N'-(1-(2-luorobenzyl)-5-chloro-2-oxo indoles alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (16)
Preparation method is with embodiment three, and just isatin replaces with 1-(2-bromobenzyl)-5-chlorisatide, yield 83.2%.m.p.240-243
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.07(s,2H),5.08(s,2H),6.33(d,1H,J=9.6Hz),6.35(dd,1H,J=2.4,8.8Hz),6.41(d,1H,J=2.4Hz),7.06-7.10(m,2H),7.13(d,1H,J=2.4Hz),7.18(d,1H,J=8.8Hz),7.25(t,1H,J=8.8Hz),7.35-7.38(m,1H),7.49(dd,1H,J=2.0,8.0Hz),7.69-7.71(m,1H),8.02(d,1H,J=9.6Hz),10.23(s,1H)。
Embodiment 19: the preparation of (Z)-N'-(1-(3-luorobenzyl)-5-chloro-2-oxo indoles alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (17)
Preparation method is with embodiment three, and just isatin replaces with 1-(3-bromobenzyl)-5-chlorisatide, yield 67.5%.m.p.230-233
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.04(s,2H),5.05(s,2H),6.33(d,1H,J=9.6Hz),7.06-7.09(m,2H),7.11-7.16(m,2H),7.21(d,1H,J=8.0Hz),7.26(d,1H,J=8.8Hz),7.39(d,1H,J=8.8Hz),7.46(dd,1H,J=2.4,8.0Hz),7.69-7.71(m,2H),8.01(d,1H,J=9.6Hz),10.23(s,1H)。
Embodiment 20: the preparation of (Z)-N'-(1-benzyl-5-bromo-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (18)
Preparation method is with embodiment three, and just isatin replaces with 1-benzyl-5-bromoisatin, yield 72.8%.m.p.241-244
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.02(s,2H),5.03(s,2H),6.33(d,1H,J=9.6Hz),7.02(d,1H,J=8.0Hz),7.06(dd,1H,J=2.0,8.8Hz),7.13(d,1H,J=2.0Hz),7.27-7.39(m,6H),7.58(dd,1H,J=2.4,8.0Hz),7.69(d,1H,J=8.8Hz),8.01(d,1H,J=9.6Hz),10.23(s,1H)。
Embodiment 21: the preparation of (Z)-N'-(1-(2-chlorobenzyl)-5-bromo-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (19)
Preparation method is with embodiment three, and just isatin replaces with 1-(2-chlorobenzyl)-5-bromoisatin, yield 82.4%.m.p.186-190
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.05(s,2H),5.06(s,2H),6.32(d,1H,J=9.6Hz),6.92(d,1H,J=8.8Hz),7.05(dd,1H,J=2.4,8.8Hz),7.12(d,1H,J=2.4Hz),7.26-7.35(m,4H),7.52(d,1H,J=8.0Hz),7.58(dd,1H,J=2.4,8.0Hz),7.68(d,1H,J=8.8Hz),8.01(d,1H,J=9.6Hz),10.23(s,1H)。
Embodiment 22: the preparation of (Z)-N'-(1-(4-bromobenzyl)-5-bromo-2-oxindole alkane-3-subunit)-2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide (20)
Preparation method is with embodiment three, and just isatin replaces with 1-(4-bromobenzyl)-5-bromoisatin, yield 81.2%.m.p.238-240
oC;
1HNMR(d
6-DMSO,400MHz)δ:5.00(s,2H),5.01(s,2H),6.33(d,1H,J=9.6Hz),7.01(d,1H,J=8.8Hz),7.06(dd,1H,J=2.4,8.8Hz),7.13(d,1H,J=2.4Hz),7.34(d,2H,J=8.0Hz),7.54(d,2H,J=8.0Hz),7.59(dd,1H,J=2.4,8.8Hz),7.69(d,1H,J=8.0Hz),7.76-7.81(m,1H),8.01(d,1H,J=9.6Hz),10.23(s,1H)。
Embodiment 23: the compound that embodiment prepares measures the inhibit activities of alpha-glucosidase:
This assay activity measures employing 96 orifice plate to carry out, 96 orifice plates add the phosphate buffer soln (PH=6.8) of 112 μ L, add the alpha-glucosidase phosphate buffer soln 20 μ L of 0.2U/mL again, the DMSO solution of 8 μ L samples, mixing is placed on 37 DEG C of constant temperature culture 15 minutes, add the substrate PNGP phosphate buffer soln of 20 μ L2.5mmol/L, mixing is placed on 37 DEG C of constant temperature culture 15 minutes.The last Na adding 0.2mol/L again
2cO
3solution 80 μ L, mixing is placed on 37 DEG C of constant temperature culture 5 minutes.Microplate reader is adopted to measure light absorption value at 405nm wavelength place again.This experiment adopts marketed drug acarbose as positive control.
Sample to the calculation formula of alpha-glucosaccharase enzyme inhibition rate is:
Inhibiting rate (%)=(1-sample/A contrast) * 100%
Sample to the height of alpha-glucosidase activity with IC
50represent, IC
50less, the activity of this compound is higher, the results are shown in Table 1.
Table 1. tonka bean camphor-isatin type compound Inhibiting α-glucosidase active testing result (IC
50).
It is active that most of tonka bean camphor as can be seen from Table 1-isatin type compound has good Inhibiting α-glucosidase, wherein compound 4,6,7,9,10,11,12,13,16,17,18,19,20 pairs of alpha-glucosidases have extraordinary inhibit activities, restraining effect effect is better than marketed drug acarbose, and activity is 300-400 times of acarbose.
Above-mentioned just preferred embodiment of the present invention, not does any pro forma restriction to the present invention.Any those of ordinary skill in the art, when not departing from technical solution of the present invention scope, can utilize the technology contents of above-mentioned announcement to make many possible variations and modification to technical solution of the present invention, or being revised as the Equivalent embodiments of equivalent variations.Therefore, every content not departing from technical solution of the present invention, according to the technology of the present invention essence to any simple modification made for any of the above embodiments, equivalent variations and modification, all should drop in the scope of technical solution of the present invention protection.
Claims (3)
1. tonka bean camphor-isatin type compound, is characterized in that: this compound has structure as shown in the formula (I):
（I）
Wherein: R
1, R
2, R
3or R
4for hydrogen, halogen, alkyl, amino, alkylamino, alkoxyl group, cyano group, nitro, hydroxyl, trifluoromethyl or sulfydryl, R
1for hydrogen, alkyl, benzyl or substituted benzyl.
2. a preparation method for tonka bean camphor-isatin type compound, is characterized in that comprising following step:
Step 1: umbelliferone, ethyl bromoacetate, salt of wormwood are placed in round-bottomed flask, add acetone, back flow reaction 5 ~ 24 hours, stopped reaction, cool to room temperature, cross and filter salt of wormwood, filtrate is spin-dried for, and obtains white solid powder ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester with ethyl alcohol recrystallization; The mol ratio of described umbelliferone, ethyl bromoacetate, salt of wormwood is 1:(1 ~ 5): (1 ~ 4);
Step 2: ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester, hydrazine hydrate are placed in round-bottomed flask, add ethanol, back flow reaction 2 ~ 10, stopped reaction, cool to room temperature, filter, obtain 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide; Described ethyl 2-((2-oxo-2H-chromene-7-base) oxygen base) acetic ester, the mol ratio of hydrazine hydrate are 1:(1 ~ 20);
Step 3: 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide, replacement isatin are placed in round-bottomed flask, add methyl alcohol and glacial acetic acid, back flow reaction 0.5 ~ 4 hour, cool to room temperature, there is solid to separate out, filter to obtain tonka bean camphor-isatin type compound (I); The mol ratio of described 2-((2-oxo-2H-chromene-7-base) oxygen base) acethydrazide, replacement isatin is 1:(1 ~ 5).
3. a class tonka bean camphor-isatin type compound according to claim 1 is preparing the application in antidiabetic medicine.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105541808A (en) * | 2016-02-04 | 2016-05-04 | 吉首大学 | Metronidazole-isatin type compound as well as preparation method and application thereof |
| CN106946759A (en) * | 2017-03-22 | 2017-07-14 | 中南大学 | 2 indolone derivatives and its p-Coumaric acid and synthetic method and purposes |
| CN107098888A (en) * | 2017-05-24 | 2017-08-29 | 遵义医学院 | The preparation method of the ketone of 3 hydroxyl 3 (base of 4 hydroxyl, 2 oxygen, 2 hydrogen chromene 3) indoline 2 |
| CN110156762A (en) * | 2019-06-12 | 2019-08-23 | 山西大学 | Gathering induced luminescence material and preparation method containing quinoline and cumarin functional group |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6423818B1 (en) * | 1999-07-30 | 2002-07-23 | Takehisa Matsuda | Coumarin endcapped absorbable polymers |
| WO2003037328A1 (en) * | 2001-10-30 | 2003-05-08 | Applied Research Systems Ars Holding N.V. | Oxindole hydrazide modulators of protein tyrosine phosphatases (ptps) |
| CN104817552A (en) * | 2015-05-04 | 2015-08-05 | 吉首大学 | Preparing method of (E)-N'-arylmethylene-4-(coumarin-3-yl)thiazole-2-hydrazide compound and its application |
| CN104829608A (en) * | 2015-05-18 | 2015-08-12 | 吉首大学 | Coumarin-thiazole-indolone compounds, and preparation method and application thereof |
-
2015
- 2015-10-27 CN CN201510702207.8A patent/CN105237521B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6423818B1 (en) * | 1999-07-30 | 2002-07-23 | Takehisa Matsuda | Coumarin endcapped absorbable polymers |
| WO2003037328A1 (en) * | 2001-10-30 | 2003-05-08 | Applied Research Systems Ars Holding N.V. | Oxindole hydrazide modulators of protein tyrosine phosphatases (ptps) |
| CN104817552A (en) * | 2015-05-04 | 2015-08-05 | 吉首大学 | Preparing method of (E)-N'-arylmethylene-4-(coumarin-3-yl)thiazole-2-hydrazide compound and its application |
| CN104829608A (en) * | 2015-05-18 | 2015-08-12 | 吉首大学 | Coumarin-thiazole-indolone compounds, and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| AHMED A. AL-AMIERY，ET AL.: ""The Use of Umbelliferone in the Synthesis of New Heterocyclic Compounds"", 《MOLECULES》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105541808A (en) * | 2016-02-04 | 2016-05-04 | 吉首大学 | Metronidazole-isatin type compound as well as preparation method and application thereof |
| CN106946759A (en) * | 2017-03-22 | 2017-07-14 | 中南大学 | 2 indolone derivatives and its p-Coumaric acid and synthetic method and purposes |
| CN106946759B (en) * | 2017-03-22 | 2020-02-14 | 中南大学 | 2-indolone derivative and ring-opened derivative thereof, and synthesis method and application thereof |
| CN107098888A (en) * | 2017-05-24 | 2017-08-29 | 遵义医学院 | The preparation method of the ketone of 3 hydroxyl 3 (base of 4 hydroxyl, 2 oxygen, 2 hydrogen chromene 3) indoline 2 |
| CN110156762A (en) * | 2019-06-12 | 2019-08-23 | 山西大学 | Gathering induced luminescence material and preparation method containing quinoline and cumarin functional group |
| CN110156762B (en) * | 2019-06-12 | 2021-12-31 | 山西大学 | Aggregation-induced emission material containing quinoline and coumarin functional groups and preparation method thereof |
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