CN102234506A - Purpose of 1,8-naphthalimide derivatives - Google Patents
Purpose of 1,8-naphthalimide derivatives Download PDFInfo
- Publication number
- CN102234506A CN102234506A CN2010101558905A CN201010155890A CN102234506A CN 102234506 A CN102234506 A CN 102234506A CN 2010101558905 A CN2010101558905 A CN 2010101558905A CN 201010155890 A CN201010155890 A CN 201010155890A CN 102234506 A CN102234506 A CN 102234506A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- alkyl
- acetyltransferase
- fluorescence
- 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
Images
Landscapes
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The invention relates to a purpose of 1,8-naphthalimide derivatives. 3-amino-1,8-naphthalimide derivatives are N-alkyl or substituted alkyl. A 3-amino-1,8-naphthalimide compound can be used as a fluorescence probe for detecting activity of N-acetyltransferase2. According to the invention, a base is established for treating tumour in a customized administration mode.
Description
Technical field
The present invention relates to a kind ofly 1, the purposes of 8-naphthalimide analog derivative specifically, relates to a kind of 3-amino-1, the purposes of 8-naphthalimide analog derivative.
Background technology
N-acetyltransferase 2 (N-acetyltransferase2; NAT.) be a kind of important phase II metabolic enzyme in the human body; mainly being the catalysis acetyl group transfers on its effect substrate aromatic amine and the heterocyclic amine material from acetyl-CoA, plays an important role in the metabolic process of human body to the activation of aromatic amine carcinogenic substance and/or deactivation and some drugs.
But the genetic polymorphism of NAT. and tissue specific expression add the interaction between environmental factors and the NAT. gene, caused the active greatest differences of NAT. of different crowd jointly, thereby the clinical administration amount has been proposed great challenge.Thereby measure the activity of individual NAT. by simple but effective method, thus determine suitable dosage, this has great importance to improving tumour patient and curing and reduce the side effect aspect.
At present, the active method that is used to detect N-acetyltransferase 2 mainly is to determine enzyme work by the meta-bolites (as sulfonamides compound) that HPLC detects known compound, perhaps use radioelement, fluorophor labeling polypeptide chain, by polymerase chain reaction (PCR) gene type of Different Individual is detected (Clin.Chem., 2004.50 (7): p.1264-6; Analytical Biochemistry 1985,145,367-75).The main drawback of these methods is a length consuming time, trivial operations.Therefore study easy, efficient and efficiently N-acetyltransferase 2 probes crucial meaning is arranged.
Summary of the invention
Existing known aromatic amine compounds can produce corresponding amide compounds (a.T.B.Felder under N-acetyltransferase 2 (NAT.) effect, M.A.McLean, M.L.Vestal, K.Lu, D.Farquhar, S.S.Legha, R.Shah and R.A.Newman, Drug Metab.Dispos., 1987,15,773; B.M.F.Brana and A.Ramos, Curr.Med.Chem.Anticancer Agents, 2001,1,237.).If the gained amides possesses fluorescence and has higher fluorescence quantum yield, then can be used for to reach nmole rank (10nM) to detection and its detectability of N-acetyltransferase 2.In view of the above; the present inventor finds behind a large amount of screening compounds: have a kind of N-to replace; 3-amino-1,8-naphthoyl imide compounds (wherein the substituting group on the N is: alkyl or substituted alkyl) has high sensitivity and capability of fast response to N-acetyltransferase 2.
Spectrum test shows: this kind N-replaces; 3-amino-1; the 8-naphthoyl imide compounds is under N-acetyltransferase 2 (buffer solution system of pH=7.4) effect; after the excitation with certain wavelength; the product that can occur after tangible emission peak and the acetylize has higher fluorescence quantum yield, can reach the nmole rank to the detectability of N-acetyltransferase 2.
Bioassay shows: this kind N-replaces; 3-amino-1; the 8-naphthoyl imide compounds has higher specificity, high sensitivity and the ability of response fast to N-acetyltransferase 2, can be to supply a model basis and determine that according to the activity of N-acetyltransferase 2 in the different patient bodies different dosages makes basis for estimation of phase II metabolic in the body of aromatic amine and hydrazine class compound.
The present invention is said to be used to detect N-acetyltransferase 2 active 3-amino-1, and 8-naphthalimide analog derivative has structure shown in the formula I:
Among the formula I: R
1Be C
1～C
6The C of alkyl or replacement
1～C
6Alkyl;
The C of said replacement
1～C
6The substituting group of alkyl is selected from: hydroxyl, alkoxyl group or R
2NR
3In a kind of, two or more, R wherein
2And R
3Be selected from H or C respectively
1～C
6A kind of in the alkyl.
In optimized technical scheme of the present invention, R
1Be C
1～C
4The C of alkyl or replacement
1～C
4Alkyl;
The C of said replacement wherein
1～C
4The substituting group of alkyl is selected from: hydroxyl, C
1～C
3Alkoxyl group or R
2NR
3In a kind of, two or more, R
2And R
3Be selected from H or C respectively
1～C
3A kind of in the alkyl.
In a further preferred technical solution of the present invention, R
1Be C
4The C of alkyl or replacement
1～C
3Alkyl;
The C of said replacement wherein
1～C
3The substituting group of alkyl is selected from: hydroxyl, CH
3NCH
3Or C
1～C
2A kind of in the alkoxyl group, two or more.
Best R
1Be normal-butyl [CH
2(CH
2)
2CH
3],
Or
Description of drawings
Fig. 1 is absorption and the emmission spectrum figure of compound in the Tris-HCl (containing 1%DMSO) of pH=7.4 damping fluid shown in the formula Ia;
Wherein: (a) be the abosrption spectrogram of compound in Tris-HCl (containing 1%DMSO) damping fluid shown in the formula Ia;
(b) be the emmission spectrum figure of compound in Tris-HCl (containing 1%DMSO) damping fluid shown in the formula Ia.
Fig. 2 is absorption and the emmission spectrum figure of Compound I a-1 in the Tris-HCl (containing 1%DMSO) of pH=7.4 damping fluid;
Wherein: (a) be the abosrption spectrogram of Compound I a-1 in Tris-HCl (containing 1%DMSO) damping fluid;
(b) be the emmission spectrum figure of Compound I a-1 in Tris-HCl (containing 1%DMSO) damping fluid.
(b-1) be the graph of a relation of the intensity of fluorescence emission spectrum and its concentration of Compound I a.
Fig. 2 is absorption and the emmission spectrum figure of Compound I a-1 in the Tris-HCl (containing 1%DMSO) of pH=7.4 damping fluid;
Wherein: (a) be the abosrption spectrogram of Compound I a-1 in Tris-HCl (containing 1%DMSO) damping fluid;
(b) be the emmission spectrum figure of Compound I a-1 in Tris-HCl (containing 1%DMSO) damping fluid;
(b-1) graph of a relation of the intensity of the fluorescence emission spectrum of Compound I a-1 and its concentration.
Fig. 3 for compound shown in the formula Ia in the Tris-HCl (containing 1%DMSO) of pH=7.4 damping fluid by N-acetyltransferase 2 catalytic fluorescence spectrum figure.
Wherein: (a) for compound concentrations shown in the formula Ia is 10 μ M, the concentration of acetyl-CoA is 50 μ M, and the concentration of N-acetyltransferase 2 is 5 μ g/mL, and illustration (figure a-1) is the dependence graph of catalysis time and fluorescence intensity under the condition for this reason;
(b) for compound concentrations shown in the formula Ia is 10 μ M, the concentration of acetyl-CoA is 50 μ M, and the concentration of N-acetyltransferase 2 is 2.5 μ g/mL, and illustration (figure b-1) is the dependence graph of catalysis time and fluorescence intensity under the condition for this reason;
(c) for compound concentrations shown in the formula Ia is 10 μ M, the concentration of acetyl-CoA is 50 μ M, and the concentration of N-acetyltransferase 2 is 1.25 μ g/mL, and illustration (figure c-1) is the dependence graph of catalysis time and fluorescence intensity under the condition for this reason;
(d) for compound concentrations shown in the formula Ia is 10 μ M, the concentration of acetyl-CoA is 50 μ M, and the concentration of N-acetyltransferase 2 is 1 μ g/mL, and illustration (figure d-1) is the dependence graph of catalysis time and fluorescence intensity under the condition for this reason;
(e) graph of a relation of the fluorescence intensity of compound shown in different concns N-acetyltransferase 2 and the formula Ia.
Fig. 4. be the metabolism fluorescence imaging figure of compound shown in the formula Ia in the HepG2 cell.
Wherein: (a) represent compound shown in the formula Ia to add the picture under the light field behind the HepG2 cell 45min; (b) represent compound shown in the formula Ia to add the picture of gathering at the 535-600nm wave band behind the HepG2 cell 45min; (c) represent compound shown in the formula Ia to add the picture of gathering at the 430-495nm wave band behind the HepG2 cell 45min; (d) represent compound shown in the formula Ia to add the picture under the light field under the HepG2 cell 90min; (e) represent compound shown in the formula Ia to add the picture of gathering at the 535-600nm wave band behind the HepG2 cell 90min; (f) represent compound shown in the formula Ia to add the picture of gathering at the 430-495nm wave band behind the HepG2 cell 90min; (g) represent without any the picture under the light field behind the compound adding HepG2 cell 90min; (h) represent the picture of gathering at the 535-600nm wave band without any behind the compound adding HepG2 cell 90min; (i) represent the picture of gathering at the 430-495nm wave band without any behind the compound adding HepG2 cell 90min.
Fig. 5 is 460nm and the 580nm fluorescence intensity ratio that compound shown in the formula Ia adds HepG2 cell front and back
Wherein Gr represents the average cell fluorescence intensity of the picture of 535-600nm wave band collection; Bl represents the average cell fluorescence intensity of the picture of 430-495nm wave band collection; Ra represents the average cell fluorescence intensity of the picture that the 430-495nm wave band gathers and the average cell fluorescence intensity ratio of the picture that the 535-600nm wave band is gathered.All numerical value are by ImageJ computed in software gained.
Embodiment
A kind of preparation 3-amino-1 of the present invention, the method for 8-naphthalimide analog derivative, its preparation route is as follows:
Key step is: 3-amino-1,8-naphthalene acid anhydride (compound shown in the formula II), aminated compounds (R
1-NH
2) and organic solvent (as ethanol and/or N, N-dimethyl-ethylenediamine etc.) under reflux state, reacted 2 hours～8 hours, successively after steam removing organic solvent, filtration and column chromatography target compound (compound shown in the formula I).
Wherein: 3-amino-1,8-naphthalene acid anhydride are by 3-nitro-1, and the reduction of 8-naphthalene acid anhydride is [as adopting the inferior tin (SnCl of chlorine
2)/hydrochloric acid reduction etc.] make (Bioorganic﹠amp; Medicinal Chemistry Letters, 15 (7), 1769-1772; 2005)
The present invention is further elaborated below by embodiment, and its purpose only is better to understand content of the present invention.Therefore, protection scope of the present invention is not limited by the cases cited.
In 50ml single port flask, add 0.5g (3mmol) 3-amino-1 successively, 8-naphthalene acid anhydride, 0.3mL (2.9mmol) N; N-dimethyl-ethylenediamine and 25ml ethanol, under argon shield, alcohol reflux; TLC follows the tracks of reaction, up to reacting completely about 1 hour of reaction times.The reduced vacuum rotary evaporation removes and desolvates, and obtains the red-brown solid.Separate (developping agent (v/v): CH with silica gel column chromatography
2Cl
2: CH
3OH=20: 1), collect the material of yellow hyperfluorescence bands of a spectrum, rotary evaporation falls solvent and obtains the solid head product, obtains the glassy yellow solid with ethyl alcohol recrystallization again.Productive rate is 75%, fusing point:＞300 ℃.
1H-NMR(D
6-DMSO)：?
(6H，s，N(CH
3)
2)，2.49(2H，t，J＝7.2Hz，CH
2CH
2N(CH
3)
2)，4.07(2H，s，-NH
2)，4.25(2H，t，J＝7.2Hz，CH
2CH
2N(CH
3)
2)，7.22(1H，d，J＝2.1Hz，)，7.53(1H，t，J＝7.8Hz)，7.85(1H，d，J＝2.1Hz)，7.94(1H，d，J＝7.8Hz)，8.24(1H，d，J＝7.8Hz).
13C-NMR(D
6-DMSO)：?
45.3，56.4，111.6，120.4，121.6，121.6，122.4，125.3，126.8，131.4，133.4，147.8，163.4and?163.4.EI-MS：58(100)；71(31)and?283(6).ESI-MS(+)：239(15)and?284(M+H，10)。
In 50ml single port flask, add 0.5g (3mmol) 3-amino-1 successively, 8-naphthalene acid anhydride, 640mg (2.9mmol) n-Butyl Amine 99 and 25ml ethanol, under argon shield, alcohol reflux, TLC follows the tracks of reaction, up to reacting completely about 1 hour of reaction times.The reduced vacuum rotary evaporation removes and desolvates, and obtains the red-brown solid.Separate (developping agent (v/v): CH with silica gel column chromatography
2Cl
2: CH
3OH=80: 1), collect the material of yellow hyperfluorescence bands of a spectrum, rotary evaporation falls solvent and obtains the solid head product, obtains the glassy yellow solid with ethyl alcohol recrystallization again.Productive rate is 80%, fusing point:＞300 ℃.
In 50ml single port flask, add 0.2g (0.94mmol) 3-amino-1 successively, 8-naphthalene acid anhydride, 0.125mL (1.25mmol) 2-(2-monoethanolamine) ethanol and 25ml ethanol; under argon shield, alcohol reflux, TLC follows the tracks of reaction; up to reacting completely about 1h of reaction times.The reduced vacuum rotary evaporation removes and desolvates, and obtains the red-brown solid.Separate (developping agent: CH with silica gel column chromatography
2Cl
2: CH
3OH=80: 1), collect the material of yellow hyperfluorescence bands of a spectrum, rotary evaporation falls solvent and obtains the solid head product, obtains the glassy yellow solid with ethyl alcohol recrystallization again.Productive rate is 80%, fusing point:＞300 ℃.
1H?NMR(400MHz，DMSO-d
6)δ8.62(d，1H，J＝8.0Hz)，8.43(d，1H，J＝8.0Hz)，8.19(d，1H，J＝8.4Hz)，7.65(t，1H，J＝8.1Hz)，7.448(s，2H)，6.84(d，1H，J＝8.4Hz)，4.58(s-br，1)，4.21(t，2H，J＝6.0Hz)，3.57(s，2H，J＝6.0Hz)，3.45(m，4H).
13C-NMR(100MHz，DMSO-d
6)δ：164.3，163.4，153.3，134.5，131.6，132.0，129.9，124.4，122.1，179.8，108.6，107.8，72.3，67.5，60.6，38.8。
The spectrum property test of compound:
1) mensuration of ultraviolet and fluorescence spectrum
After vacuum-drying, accurate weighing sample on the balance (being accurate to 0.0001 gram) with dimethyl sulfoxide (DMSO) (DMSO) constant volume, is made into 10 with compound shown in formula Ia, formula Ib and the formula Ic
-3The solution of M and constant volume are in the 10mL volumetric flask, and as mother liquor, Compound I a, compounds ib and the Compound I c solution of preparation different concns is used for absorption spectrum and excite-test of emmission spectrum.
2) mensuration of fluorescence quantum yield
The relative fluorescence quantum yield Φ of compound shown in formula Ia, formula Ib and the formula Ic
sBe quinoline sulfate (Φ with 0.5mol
Ref=0.55) solution is that reference records, and the result gets the mean value of measuring three times, calculates by (1) formula:
Φ
s＝Φ
ref.A
ref.F
s/(F
ref.A
s) (1)
In the formula: Φ
s, Φ
RefThe fluorescence quantum yield of representing testing sample and standard substance respectively; A
s, A
RefRepresent testing sample and standard substance radiative absorbancy respectively to this excitation wavelength; F
s, F
RefThe integration fluorescence intensity of representing testing sample and standard substance respectively.
Concrete outcome sees that Fig. 1 (is absorption and the emmission spectrum figure of compound in the Tris-HCl (containing 1%DMSO) of pH=7.4 damping fluid shown in the formula I a, the collection of illustrative plates of compound is similar, unlisted shown in formula Ib and the formula Ic) and see Table 1 (compound is at the spectroscopic data of Tris-HCl (containing 1%DMSO) damping fluid shown in formula Ia, formula Ib and the formula Ic).
Table 1
By among Fig. 1 (b-1) as can be known: the intensity of the fluorescence emission spectrum of Compound I a and concentration have extraordinary linear light relation.
Respectively " meta-bolites " of compound shown in synthesis type Ia, formula Ib and the formula Ic, as follow these steps to make " meta-bolites " of compound shown in the formula Ia.
The mixing solutions (its volume ratio is 1: 1) that in 25ml single port flask, adds compound shown in the formula Ia of 283mg (10mmol) and 4mL pyridine and diacetyl oxide successively.After stirring 24 hours under room temperature (20 ℃～25 ℃) condition, raw material reaction was complete when TLC point plate was followed the tracks of.The reduced vacuum rotary evaporation removes and to desolvate, and obtains yellow oily liquid, this oily liquids is dissolved in about 50mL chloroform, and with the water washing organic phase of 2 * 50mL, collects organic phase and also use the anhydrous sodium sulphate dried overnight.The chloroform rotary evaporation that reduces pressure is removed with re-crystallizing in ethyl acetate and can be got 2.76g lark solid, and productive rate is 85%.
1HNMR(CDCl3)：δ＝2.27(3H，s，)，2.53(6H，s，)，2.92(2H，t，J＝6.0Hz)，4.38(2H，t，J＝6.0Hz，)，7.65(1H，t，J＝8.0Hz)，7.90(1H，d，J＝8.0Hz)，7.94(1H，s)，8.35(1H，d，J＝7.8Hz)，8.54(1H，s)，8.59(1H，s).
13C?NMR(CDCl
3)：δ＝24.7，37.7，46.1，58.3，120.9，121.9，122.6，122.8，124.2，127.4，129.5，132.1，133.7，136.8，163.5，164.4and?169.2.EI-MS：58(100)；71(69)；140(8)；169(7)；212(8)and?325(10).ESI-MS(+)：281(13)and?326(M+H，100)。
Because reactant and product are known substance, so those skilled in the art's instruction as stated above can make the meta-bolites of other compound.The structure of said " meta-bolites " is shown in formula III:
In the formula III, work as R
1During for normal-butyl, note by abridging and be Compound I a-1; Work as R
1For
The time, note by abridging and be compounds ib-1; Work as R
1For
The time, note by abridging and be Compound I c-1;
Compound I a-1, compounds ib-1 and Compound I c-1 are surveyed its ultraviolet (absorption) and fluorescence (emission) wavelength and fluorescence quantum yield by embodiment 4 described methods, and concrete outcome sees that (Fig. 2 is absorption and the emmission spectrum figure of Compound I a-1 in the Tris-HCl (containing 1%DMSO) of pH=7.4 damping fluid to Fig. 2; The collection of illustrative plates of compound is similar, unlisted shown in formula Ib-1 and the formula Ic-1) and table 2.
Table 2
By the intensity of the fluorescence emission spectrum of the enzymes metabolism product of Compound I a and concentration have extraordinary linear light relation as can be seen among Fig. 2 (b-1).By the fluorescence intensity ratio that can infer Compound I a and its meta-bolites among Fig. 1 (b) and Fig. 2 (b) and its concentration good linear relationship is arranged, therefore can be by fluorescence intensity two kinds of compound concentrations of deduction place and then can infer that enzyme lives indirectly.
Embodiment 6
Compound shown in formula Ia, formula Ib and the formula Ic is to the mensuration of the response of N-acetyltransferase 2:
In the micro-fluorescence cuvette of 40 μ L; we select the concentration 50 μ M of acetyl-CoA (available from Sigma company); in the Tris-HCl damping fluid (containing 1%DMSO) of pH=7.5; regulate and add N-acetyltransferase 2 (available from Sigma companies); make its ultimate density be respectively 5 μ g/mL; 2.5 μ g/mL; 1.25 μ g/mL; 1 μ g/mL; behind the N-acetyltransferase 2 solution 100 μ L that prepare each group concentration, add compound mother liquor shown in the formula Ia of 1 μ L, make compound concentrations shown in the formula Ia of adding reach 10 μ M and put into fluorophotometer rapidly and measured fluorescence intensity every 30 seconds and change.We have measured the fluorescence response of Ia to the N-acetyltransferase 2 under four groups of different concns, the results are shown in accompanying drawing 3.
Compound shown in the formula Ia is very fast to the response speed of N-acetyltransferase 2 as can be seen by Fig. 3 (a), and the obvious enhanced of the fluorescence intensity at the 410nm place reduces in the fluorescence intensity at 580nm place simultaneously.From above-mentioned test result as can be seen, compound shown in the formula Ia can be used as the proportionality fluorescent probe of N-acetyltransferase 2.Dotted line is represented the curve (R=0.9978) after the match among Fig. 3 (e), has shown good linear relationship, has illustrated since the concentration of enzyme and fluorescence intensity have good linearity to concern.
In test result, also obtained similar result to compound shown in formula Ib and the formula Ic.The obvious enhanced of fluorescence intensity at the 455nm place in compound thing shown in the formula Ib reduces in the fluorescence intensity at 566nm place simultaneously.From above-mentioned test result as can be seen, compound shown in the formula Ib can be used as the proportionality fluorescent probe of N-acetyltransferase 2.The obvious enhanced of fluorescence intensity at the 460nm place in compound thing shown in the formula Ic reduces in the fluorescence intensity at 570nm place simultaneously.From above-mentioned test result as can be seen, compound shown in the formula Ic can be used as the proportionality fluorescent probe of N-acetyltransferase 2.
Embodiment 7
Compound shown in formula Ia, formula Ib and the formula Ic is to the mensuration [in viable cell (HepG2) body] of the response of N-acetyltransferase 2:
HepG2 cell (Chinese Academy of Sciences's cell bank) is cultivated in 6 orifice plates, substratum adopts DEME (to contain 10% foetal calf serum, phenol red reagent, 4.5g/L D-glucose, GlutaMax-1), after cell is paved with, draw supernatant liquor, and, add compound shown in the formula Ia then with PBS damping fluid washing three times, making its ultimate density is that the content of 10 μ M and DMSO is 5.0 (V/V).Subsequently 6 orifice plates are transferred in the cell culture incubator (37 ℃, 5%CO
2), when 45 minutes and 90 minutes, respectively take out culture plate, with PBS damping fluid washed twice, remove compound shown in the formula Ia in the nutrient solution.Add PBS damping fluid (pH=7.5 again, 1%DMSO) place Leica DMIRB fluorescent microscope (being furnished with COHU high performance CCD camera lens), gather the green fluorescence (time shutter 800ms) at 430-495nm blue-fluorescence (time shutter 3000ms) and 535-600nm place respectively, the results are shown in Figure 4 and Fig. 5.
As shown in Figure 4: the accumulation number of photons at 430-495nm place blue-fluorescence strengthens along with administration timing of drug, and on the contrary the accumulation number of photons at the green fluorescence (the same) at 535-600nm place but weakens (conforming to the conclusion of embodiment 6) along with the increase of time.
In test result, also obtained similar result to compound shown in formula Ib and the formula Ic.The obvious enhanced of fluorescence intensity at the 430-495nm place in compound thing shown in the formula Ib reduces in the fluorescence intensity at 535-600nm place simultaneously.From above-mentioned test result as can be seen, compound shown in the formula Ib can be used as the viable cell proportionality fluorescent probe of N-acetyltransferase 2.The obvious enhanced of fluorescence intensity at the 430-495nm place in compound thing shown in the formula Ic reduces in the fluorescence intensity at 535-600nm place simultaneously.From above-mentioned test result as can be seen, compound shown in the formula Ic can be used as the viable cell proportionality fluorescent probe of N-acetyltransferase 2.
Claims (4)
1. compound shown in the formula I is as detecting N-acetyltransferase 2 active fluorescent probes:
Among the formula I: R
1Be C
1～C
6The C of alkyl or replacement
1～C
6Alkyl;
The C of said replacement
1～C
6The substituting group of alkyl is selected from: hydroxyl, alkoxyl group or R
2NR
3In a kind of, two or more, R wherein
2And R
3Be selected from H or C respectively
1～C
6A kind of in the alkyl.
2. purposes as claimed in claim 1 is characterized in that, wherein R
1Be C
1～C
4The C of alkyl or replacement
1～C
4Alkyl;
The C of said replacement
1～C
4The substituting group of alkyl is selected from: hydroxyl, C
1～C
3Alkoxyl group or R
2NR
3In a kind of, two or more, R
2And R
3Be selected from H or C respectively
1～C
3A kind of in the alkyl.
3. purposes as claimed in claim 2 is characterized in that, wherein R
1Be C
4The C of alkyl or replacement
1～C
3Alkyl;
The C of said replacement
1～C
3The substituting group of alkyl is selected from: hydroxyl, CH
3NCH
3Or C
1～C
2A kind of in the alkoxyl group, two or more.
4. purposes as claimed in claim 3 is characterized in that, wherein R
1For normal-butyl,
Or
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101558905A CN102234506B (en) | 2010-04-23 | 2010-04-23 | Purpose of 1,8-naphthalimide derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101558905A CN102234506B (en) | 2010-04-23 | 2010-04-23 | Purpose of 1,8-naphthalimide derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102234506A true CN102234506A (en) | 2011-11-09 |
| CN102234506B CN102234506B (en) | 2013-11-13 |
Family
ID=44885642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101558905A Expired - Fee Related CN102234506B (en) | 2010-04-23 | 2010-04-23 | Purpose of 1,8-naphthalimide derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102234506B (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102617573A (en) * | 2012-02-23 | 2012-08-01 | 北京大学 | 9-substituted triazole para-naphthalimide derivative, preparation method thereof and application |
| CN102719111A (en) * | 2012-05-25 | 2012-10-10 | 大连理工大学 | 1,8-naphthalene dinitrile fluorescent dichroic dyes containing amido bond, preparation method for 1,8-naphthalene dinitrile fluorescent dichroic dyes and application of 1,8-naphthalene dinitrile fluorescent dichroic dyes |
| CN105968170A (en) * | 2016-06-12 | 2016-09-28 | 安阳师范学院 | Fluorescent probe substrate of dipeptidyl peptidase IV as well as preparation method and application of fluorescent probe substrate |
| CN106867271A (en) * | 2015-12-11 | 2017-06-20 | 中国科学院大连化学物理研究所 | The naphthalimide fluorescent dyestuff and its synthetic method and application of a kind of big Stokes shift and launch wavelength long |
| CN108801992A (en) * | 2018-04-25 | 2018-11-13 | 中国科学院生物物理研究所 | Fe3+Molecular fluorescence sensor and preparation method thereof |
| CN110954515A (en) * | 2019-12-03 | 2020-04-03 | 山西大学 | 1, 8-naphthalimide derivative and application thereof |
| CN112939863A (en) * | 2019-12-10 | 2021-06-11 | 中国科学院大连化学物理研究所 | High-brightness and high-light stability lipid drop fluorescent probe and synthetic method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101684094A (en) * | 2008-09-24 | 2010-03-31 | 中国科学院上海药物研究所 | 3-substituted-1, 8-naphthalimide compound and synthesis method and medical application thereof |
-
2010
- 2010-04-23 CN CN2010101558905A patent/CN102234506B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101684094A (en) * | 2008-09-24 | 2010-03-31 | 中国科学院上海药物研究所 | 3-substituted-1, 8-naphthalimide compound and synthesis method and medical application thereof |
Non-Patent Citations (1)
| Title |
|---|
| FEDERICO INNOCENTI等: "PHARMACOGENETICS OF ANTICANCER AGENTS: LESSONS FROM AMONAFIDE", 《DRUG METABOLISM AND DISPOSITION》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102617573A (en) * | 2012-02-23 | 2012-08-01 | 北京大学 | 9-substituted triazole para-naphthalimide derivative, preparation method thereof and application |
| CN102617573B (en) * | 2012-02-23 | 2014-09-17 | 北京大学 | 9-substituted triazole para-naphthalimide derivative, preparation method thereof and application |
| CN102719111A (en) * | 2012-05-25 | 2012-10-10 | 大连理工大学 | 1,8-naphthalene dinitrile fluorescent dichroic dyes containing amido bond, preparation method for 1,8-naphthalene dinitrile fluorescent dichroic dyes and application of 1,8-naphthalene dinitrile fluorescent dichroic dyes |
| CN106867271A (en) * | 2015-12-11 | 2017-06-20 | 中国科学院大连化学物理研究所 | The naphthalimide fluorescent dyestuff and its synthetic method and application of a kind of big Stokes shift and launch wavelength long |
| CN105968170A (en) * | 2016-06-12 | 2016-09-28 | 安阳师范学院 | Fluorescent probe substrate of dipeptidyl peptidase IV as well as preparation method and application of fluorescent probe substrate |
| CN105968170B (en) * | 2016-06-12 | 2018-10-30 | 安阳师范学院 | A kind of the fluorescence probe substrate and preparation method and application of DPP IV |
| CN108801992A (en) * | 2018-04-25 | 2018-11-13 | 中国科学院生物物理研究所 | Fe3+Molecular fluorescence sensor and preparation method thereof |
| CN108801992B (en) * | 2018-04-25 | 2019-08-02 | 中国科学院生物物理研究所 | Fe3+Molecular fluorescence sensor and preparation method thereof |
| CN110954515A (en) * | 2019-12-03 | 2020-04-03 | 山西大学 | 1, 8-naphthalimide derivative and application thereof |
| CN110954515B (en) * | 2019-12-03 | 2020-11-10 | 山西大学 | 1, 8-naphthalimide derivative and application thereof |
| CN112939863A (en) * | 2019-12-10 | 2021-06-11 | 中国科学院大连化学物理研究所 | High-brightness and high-light stability lipid drop fluorescent probe and synthetic method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102234506B (en) | 2013-11-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102234506B (en) | Purpose of 1,8-naphthalimide derivatives | |
| Li et al. | A new GFP fluorophore-based probe for lysosome labelling and tracing lysosomal viscosity in live cells | |
| Gu et al. | Detection of endogenous hydrogen peroxide in living cells with para-nitrophenyl oxoacetyl rhodamine as turn-on mitochondria-targeted fluorescent probe | |
| Tatarets et al. | Synthesis of novel squaraine dyes and their intermediates | |
| EP3564239B1 (en) | Aryl hydrocarbon receptor modulator | |
| Plsikova et al. | 3, 6-Bis (3-alkylguanidino) acridines as DNA-intercalating antitumor agents | |
| Hu et al. | Curcumin-based polarity fluorescent probes: Design strategy and biological applications | |
| Islam et al. | Fluorescein hydrazones: A series of novel non-intercalative topoisomerase IIα catalytic inhibitors induce G1 arrest and apoptosis in breast and colon cancer cells | |
| CN106146611B (en) | It is a kind of measure dipeptidyl peptidase IV activity fluorescence probe substrate and its application | |
| CN104945322A (en) | Compound for detecting tumor hypoxia and preparation method thereof | |
| Gao et al. | Development of a two-photon carbazole derivative probe for fluorescent visualization of G-quadruplex DNA in cells | |
| Sović et al. | Synthesis, antitumor activity and DNA binding features of benzothiazolyl and benzimidazolyl substituted isoindolines | |
| Plater et al. | The synthesis and evaluation of o-phenylenediamine derivatives as fluorescent probes for nitric oxide detection | |
| CN105367566B (en) | Substituted cumarin-thiazole orange derivative and its preparation method and application | |
| Ma et al. | Novel polypyridyl ruthenium complexes acting as high affinity DNA intercalators, potent transcription inhibitors and antitumor reagents | |
| CN105670608B (en) | High-selectivity fluorescent probe capable of detecting nickel ions in mitochondria of living cells and preparation method thereof | |
| Zonjić et al. | Styryl dyes with N-Methylpiperazine and N-Phenylpiperazine Functionality: AT-DNA and G-quadruplex binding ligands and theranostic agents | |
| CN104650610A (en) | Asymmetric near-infrared BODIPY fluorescent dye as well as preparation method and application thereof | |
| Jin et al. | Synthesis of fluorescent G-quadruplex DNA binding ligands for the comparison of terminal group effects in molecular interaction: Phenol versus methoxybenzene | |
| Niu et al. | Development of triphenylamine-based fluorescent probe with a large Stokes’ shift suitable for locating mitochondria | |
| CN109180716A (en) | A kind of multi signal Ratio-type differentiation detection H2O2And H2Design, synthesis and the application of the fluorescence probe of S | |
| EP2397464B1 (en) | Synthesis of novel azo-dyes and their use in oligonucleotide synthesis | |
| Fukumoto et al. | Acid responsiveness of emissive morpholinyl aminoquinolines and their use for cell fluorescence imaging | |
| CN113995758B (en) | Application of carbazole-pyrimidine derivative in preparation of antitumor drugs | |
| CN110343126B (en) | Pyridine/pyridine quaternary ammonium salt substituted BODIPY compound and application thereof |
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 |
Granted publication date: 20131113 Termination date: 20160423 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |