CN106866576B - 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one compound and application - Google Patents
2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one compound and application Download PDFInfo
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- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 title claims abstract description 20
- -1 thiazolidin-4-one compound Chemical class 0.000 title description 11
- 102000003984 Aryl Hydrocarbon Receptors Human genes 0.000 claims abstract description 19
- 108090000448 Aryl Hydrocarbon Receptors Proteins 0.000 claims abstract description 19
- NOLHRFLIXVQPSZ-UHFFFAOYSA-N 1,3-thiazolidin-4-one Chemical compound O=C1CSCN1 NOLHRFLIXVQPSZ-UHFFFAOYSA-N 0.000 claims abstract description 14
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- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
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- 150000003935 benzaldehydes Chemical class 0.000 description 1
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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
- C07D277/54—Nitrogen and either oxygen or sulfur atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of compound of class containing thiazole heterocycle, which is 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one, and abbreviation TNTO, chemical structure is as shown in logical formula (I).Application the invention also discloses the compound as aryl hydrocarbon receptor agonist.Experiment confirms, the compound of class containing thiazole heterocycle of the invention can significantly raise gene, the protein expression of the related allogenic material metabolic enzyme CYP1A1 of aryl hydrocarbon receptor downstream target gene in murine hepatocarcinoma cell under 10 μM of concentration, prompting the compound is the agonist of aryl hydrocarbon receptor, being expected to become potentially is the drug for treating tumor targets with aryl hydrocarbon receptor, has extensive potential applicability in clinical practice and economic development value.
Description
Technical field
The present invention relates to a kind of compound of class containing thiazole heterocycle and its application more particularly to a kind of 2- (4- trifluoromethylbenzenes
Imido grpup) -5- (2- naphthalenyhnethylene) thiazolidin-4-one compound and its application as aryl hydrocarbon receptor agonist；Belong to doctor
Medicine chemical field.
Background technique
Aryl hydrocarbon receptor (aryl hydrocarbon receptor, AhR) is basic helix-loop-helix (basic
One of helix-loop-helix, bHLH) super subfamily bHLH-PAS (Bhlh-PER-ARNT-SIM) member, it is in the family
It uniquely can be by the receptor of ligand activation.Evolutionary analysis shows AhR gene in mammal, amphibian, reptile and bird
There is presence in class.It is also deposited in the various tissues such as the liver of human body, lung, kidney, placenta, tonsillotome, bone-marrow-derived lymphocyte and cell
?.AhR is as a kind of ligand-activated transcription factor, I phase (CYP1) of major regulatory reconstituted cytochrome P-450 enzyme system family and some II
The expression of phase metabolic enzyme participates in the metabolic process of some drugs and poisonous substance.Meanwhile AhR also has many endogenous sexual functions, such as adjusts
Control cell cycle, immune response, cell differentiation and circadian rhythm etc..
Some researches show that aryl hydrocarbon receptors can influence to swell by participating in the processes such as Cell apoptosis and proliferation, immune metabolism
Growth, life, migration and the invasion of tumor.AhR has double action to the regulation of tumour, matches in polycyclic aromatic hydrocarbon, halogenated aryl hydrocarbon etc.
Under body effect, AhR can promote tumour generation；But after the compounds such as benzothiazole, amino flavones activate AhR, suppression cancer function can be played
Can, therefore using aryl hydrocarbon receptor as action target spot, finding the compound containing active nitrogen class can yet be regarded as a kind of searching antineoplastic
The means of object.
For above content, to find with aryl hydrocarbon receptor is the compound for treating tumor targets, it is necessary first to which determining should
Compound whether be aryl hydrocarbon receptor agonist.By activating the signal path of aryl hydrocarbon receptor, downstream target base can be activated
Because of the related allogenic material metabolic enzyme of (such as CYP1A1, CYP1A2, CYP1B1), the metabolism of exogenous poisonous substance can be promoted, from
And body is protected not influenced by allogenic material.Intervene antitumor signal path related to aryl hydrocarbon receptor indirectly simultaneously, prevents from swelling
The generation of tumor.Since aryl hydrocarbon receptor has a more loose ligand binding pocket, a variety of endogenous and exogenous change
Close the ligand that object is all confirmed as aryl hydrocarbon receptor.Determine a compound whether be aryl hydrocarbon receptor agonist, method
It is main horizontal to downstream related gene (CYP1A1, CYP1B1 etc.) and correlative protein expression by signal path by detecting it
It transfers to be determined on (CYP1A1, CYP1B1 etc.).But found through authoritative institution's Access point: related 2- (4- trifluoromethyl
Phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one compound and its as aryl hydrocarbon receptor agonist application at present
Both at home and abroad there is not yet report.
Summary of the invention
In view of the deficiencies of the prior art, the purpose of the present invention is to provide a kind of novel compound of class containing thiazole heterocycle, that is, 2-
(4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one compound and its as aryl hydrocarbon receptor excitement
The application of agent.
The compound of class containing thiazole heterocycle of the present invention, it is characterised in that: the compound is 2- (4- trifluoromethylbenzene imines
Base) -5- (2- naphthalenyhnethylene) thiazolidin-4-one, abbreviation TNTO (2- (4-trifluoromethyl-phenylimino) -5-
(2-naphthyl) methylene-thiazolidin-4-one), chemical structure is as shown in logical formula (I):
The preparation method of above-mentioned formula (I) compound, be by 4- 5-trifluoromethylaniline be starting material, by with ammonium thiocyanate
Reaction generates substituted benzene thiocarbamide, using the ring closure reaction with ethyl acetate, forms thiazole heterocycle, finally sends out with substituted benzaldehyde
Raw condensation reaction obtains final product, and specific synthesis step is shown in embodiment 1.
Application of the compound of class containing thiazole heterocycle of the present invention as aryl hydrocarbon receptor agonist, wherein the compound
Preferably 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one.
Experiment confirms: above-mentioned 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one, i.e.,
TNTO compound has obvious effect in terms of activating aryl hydrocarbon receptor, this provides beauty for the exploitation of novel tumor therapeutic agent
Good prospect.
The effect of substantive and of the present invention compound in order to better understand the present invention, below with reference to TNTO compound
Experiment and as a result, come be further described its activation aryl hydrocarbon receptor in effect.
The preparation of HepaWT cell: in conventional manner cultivate HepaWT cell, collect growth conditions it is good and in pair
The cell of number phase, it is spare.
1.10 μM of TNTO compound effects are after HepaWT cell 24 hours, real-time fluorescence quantitative PCR (RT-PCR) point
Analyse the expression (Fig. 1) of CYP1A1.Show 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one
Closing object causes CYP1A1 gene expression amount to raise.
2.10 μM of TNTO compound effects are after HepaWT cell 24 hours, immunoblotting (Western Blot)
Analyze the expression (Fig. 2) of CYP1A1 albumen.Show 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidine -
4- ketone compound causes CYP1A1 expressing quantity to raise.
By above-mentioned experiment and as a result, available to draw a conclusion:
Compound 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one of the present invention
It can significantly cause the expression of CYP1A1 related gene and albumen to be raised, activate aryl hydrocarbon receptor signal path.Prompt it is this containing
The aryl hydrocarbon receptor agonist of active nitrogen class is of great significance to searching by the anti-tumor drug of target spot of aryl hydrocarbon receptor.
The novel compound of class containing thiazole heterocycle, that is, 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalene disclosed by the invention
Methylene) thiazolidin-4-one compound and its as aryl hydrocarbon receptor agonist application indicate the compound be expected to become with
Aryl hydrocarbon receptor is the potential drug of the treatment tumour of target spot, has very big development and application prospect.
Detailed description of the invention
Fig. 1 is influence of the TNTO (10 μM) to CYP1A1 gene expression in HepaWT cell.
Wherein, DMSO (0.1%) is positive control, and TCDD (1nM) is negative control, TNTO (10 μM) compound.
Fig. 2 is influence of the TNTO (10 μM) to CYP1A1 protein expression in HepaWT cell.
Wherein, DMSO (0.1%) is positive control, and TCDD (1nM) is negative control, TNTO (10 μM) compound.
Specific embodiment
The preparation of embodiment 1:2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one
Hydrochloric acid solution is made into the ratio of HCl:H2O (1:4).It weighs 11.4g (150mmol) ammonium thiocyanate and is dissolved in 50mL salt
In acid solution, 12.4mL (100mmol) 4- 5-trifluoromethylaniline is added, 85 DEG C are heated under stirring condition, mixture becomes clarification,
After reaction 12 as a child, mixture after reaction, is cooled to room temperature, has sticky oily liquids to go out by TLC monitoring reaction
It is existing, it is extracted with ethyl acetate, extract liquor is successively washed with 10% hydrochloric acid solution, sodium chloride saturated solution, water, and extract liquor decompression is steamed
Except solvent, 4- trifluoromethylbenzene thiocarbamide is obtained.
4- trifluoromethylbenzene thiocarbamide 0.906mL (6.0mmol), anhydrous sodium acetate 2479mg (30mmol) are added to
In 20mL ethyl alcohol, under stirring condition, it is added ethyl chloroacetate 1.28mL (12mmol), 6 hours is then heated at 60 DEG C,
TLC detection reaction, is cooled to room temperature after reaction, precipitates.Reaction solution is filtered, solid ethanol washing obtains portion
Divide crude product, then filtrate decompression distillation is extracted with ethyl acetate and water, organic phase merges to obtain more crude products.It is thick to produce
Object recrystallizes in ethyl acetate, obtains product 2- (4- trifluoromethyl) amino -1,3-thiazoles -4- ketone.
It weighs 2- (4- trifluoromethyl) amino -1,3- thiazol -4-one 130.1mg (0.5mmol) and is dissolved in 3mL ethyl alcohol
In, it is added 2- naphthaldehyde 81.2mg (0.6mmol), 00 μ L of piperidinyl-1, on parallel projects instrument, it is small to react 24 for 60 DEG C of constant temperature oscillations
When.Reaction is monitored by TLC, is cooled to room temperature after completion of the reaction, has a large amount of precipitatings to generate during the reaction, by analysis table
Sign, precipitating are product 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one.Filtering, uses acetic acid
Ethyl ester, ethyl alcohol, petroleum ether are successively washed, if not precipitating generation, solvent is evaporated, and match by 1:2 and ethyl alcohol (acetic acid is added
Ethyl ester) or petroleum ether, oscillation is then most of to precipitate, and filters, a large amount of ethyl acetate of filter residue, ethyl alcohol, petroleum ether is successively
It is washed.Still without precipitating generate being separated by silica gel column chromatography, developping solution by different proportion ethyl acetate
It is formed with petroleum ether.
Product is yellow powder, yield 30%.
1HNMR (400MHz, DMSO): δ (ppm)=8.55 (s, 1H), 8.00~7.90 (m, 3H), 7.82 (s, 1H),
7.70 (s, 1H), 7.66~7.62 (d, 2H), 7.58~7.55 (m, 1H), 7.50~7.43 (m, 2H), 7.30~7.26 (d,
2H)；ESI-MS,C21H13F3N2OS,m/z 399.7(M+1).
The synthetic route of above-mentioned 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one is as follows:
Embodiment 2:2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one compound causes
The up-regulation verifying of CYP1A1 gene expression amount
1. HepaWT cell is seeded in the Tissue Culture Dish of diameter 60mm with the density of 1 × 105mL-1.It, will after for 24 hours
This cell respectively with 2- (4- trifluoromethylbenzene amido) -5- (2- naphthalenyhnethylene) -1,3- thiazol -4-one (10 μM), DMSO
(0.1%, negative control), TCDD (1nM, positive control) are acted on for 24 hours in 37 DEG C of under conditions ofs containing 5%CO2.
The extraction of 2.RNA: collecting cell, discard culture medium, is rinsed 2 times with the PBS solution of preheating.Suitable cracking is added
Liquid lytic cell is slowly blown and beaten several times with pipettor.Lysate is transferred in the centrifugal column being placed in 2mL collecting pipe
13000rpm is centrifuged 1 minute.It is clear under abandoning, centrifugal column is put into new 2mL collecting pipe.
700 μ L Wash Buffer 1 (plus dehydrated alcohol) are added into centrifugal column, 13000rpm is centrifuged 1 minute.It abandons
It is lower clear, 600 μ L Wash Buffer 2 (plus dehydrated alcohol) are added into centrifugal column, 13000rpm is centrifuged 1 minute.Under abandoning
Clearly, 250 μ L Wash Buffer 2 (plus dehydrated alcohol) are added into centrifugal column, 13000rpm is centrifuged 2 minutes.
Elution: centrifugal column is put into new 1.5mL centrifuge tube, the water droplet of 50-100 μ L nuclease free is taken to be added to centrifugal column
Film center, 13000rpm is centrifuged 1 minute, obtains the total rna solution of sample, marks that rear ice bath is stand-by or -70 DEG C are long-term
It saves.
The purifying of 3.RNA
DNAse I digests RNA sample, removes the genomic DNA that may contain.DNAse I will be passed through with the water of no RNA enzyme
The volume of the RNA sample (μ g of RNA≤45) of digestion is adjusted to 200 μ L.Then add 700 μ L buffer RLT, mixes well.Add
500 μ L dehydrated alcohols are gently inhaled with pipettor after playing mixing for several times, and the solution for taking 700 μ L to obtain crosses column, gently lid upper tube cap,
Room temperature 10,000rpm are centrifuged 15 seconds, remove the liquid in collecting pipe.It repeats, remaining sample is crossed into column, every time added sample body
≤ 700 μ L of product.After posts transfer to new 2mL collecting pipe, 500 μ L Buffer RPE are added to wash pillar, gently lid upper tube cap,
Room temperature 10,000rpm are centrifuged 15 seconds, remove the liquid in collecting pipe, pillar is put back in collecting pipe.Add 500 μ L, 80% ethyl alcohol
Into pillar, gently lid upper tube cap, room temperature 10,000rpm are centrifuged 2 minutes, and collecting pipe and liquid are abandoned.Posts transfer is arrived
One new 2mL collecting pipe opens the lid of pillar, and maximum (top) speed is centrifuged 5 minutes, and collecting pipe and liquid are abandoned.Elution, by column
Son is transferred to a new 1.5mL collecting pipe, takes 14 water of the μ L without RNA enzyme to be vacantly added to the film center of pillar, gently closes the lid,
Maximum (top) speed is centrifuged 1 minute eluted rna.
4. measuring the concentration of total serum IgE and evaluating it and extract quality.
Using using the water of nuclease free to return to zero before instrument NanoDrop 2000C, measure the concentration of RNA and its in 260nm and
UV absorption at 280nm.RNA extracts the ratio of quality references A260/A280, and suitable ratio range is 1.8 to 2.1.
The synthesis of 5.cDNA
After total rna concentration is leveled, using the first chain cDNA synthetic agent box by total serum IgE reverse transcription at cDNA:
A. the PCR pipe of sterile nuclease free is placed on ice, following reactants is sequentially added:
B. said mixture is put into PCR instrument, 65 DEG C are incubated for 5 minutes, and 4 DEG C are incubated for 10 minutes, and it during which prepares and is added:
C. it mixes, of short duration centrifugation.It is put into PCR instrument, 25 DEG C are incubated for 5 minutes, and 42 DEG C are incubated for 60 minutes, and 70 DEG C are incubated for 5 points
Clock terminates reaction.Mark that rear ice bath is stand-by or -30 DEG C of long-term preservations.
6.qPCR analysis
Primer: CYP1A1 5 '-TCTCGTGGAGCCTCATGTACCT-3 ' (forward primer)
5 '-TGCCGATCTCTGCCAATCA-3 ' (reverse primer)
5 '-GACGGCCAGGTCATCACTATTG-3 ' of β-actin (forward primer)
5 '-AGGAAGGCTGGAAAAGAGCC-3 ' (reverse primer)
A. according to the form below prepares PCR reaction mixture (reaction solution preparation can be carried out in room temperature),
When b.qPCR, 10 μ L RT-PCR products is taken to add 260 μ L H2O is made into 270 μ L cDNA working solutions, matches PCR by upper table
Reaction mixture: two step method is prepared, for 10 μ L systems, if there is M sample, first by Mix 5 μ L × (6M+10) and a pair
Primers 0.25 μ L × (6M+10) premixing (general each sample sets 5-6 technology and repeats), is dispensed into 5mL centrifuge tube, uses
Successively 4.5 μ L of (Mix+primers) 5.5 μ L+ (cDNA working solution) in reaction tube is added in following liquid by electron gun.
C. sealer, of short duration centrifugation 60s are posted.
The result is shown in Figure 1 shows 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one chemical combination
Object causes CYP1A1 gene expression amount to raise.
Embodiment 3:2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one compound causes
The up-regulation verifying of CYP1A1 expressing quantity
1. by HepaWT cell with 1 × 105mL-1Density be seeded in the Tissue Culture Dish of diameter 60mm.It, will after for 24 hours
This cell respectively with 2- (4- trifluoromethylbenzene amido) -5- (2- naphthalenyhnethylene) -1,3- thiazolidin-4-one (10 μM), DMSO
(5%, negative control), TCDD (1nM, positive control) contain 5%CO at 37 DEG C2Under conditions of act on for 24 hours.
Culture solution in ware is discarded, the PBS being pre-chilled with 4 DEG C is washed three times.Ware is placed on ice after PBS is abandoned only, is added
Enter 4mL PBS.With cell under cell scraper.Microscopically observation remaining cell amount.By PBS sterile hose suck sterile 15mL from
In heart pipe, 5min, 1000rpm are centrifuged under the conditions of 4 DEG C.Centrifugation removes supernatant, obtains cell mass.Add the cold PBS of 3mL, uses rifle
It dispels.Similar washing repeats three times.
Supernatant removal is clean, and every pipe adds 50 μ L lysates (1mL Ripa+10 μ L protein inhibitor
Cocktail+1 μ L 0.3%PMSF), it is dispelled, is moved on in the 1.5mL centrifuge tube being placed on ice, cell is cracked on ice with rifle
30min is vortexed primary every 10min.The liquid that cracking is finished, is centrifuged (1300rpm, 10min, 4 DEG C).Supernatant is taken,
It is saved under the conditions of -80 DEG C.The protein concentration in cell pyrolysis liquid is quantified using BCA determination of protein concentration method.
2. electrophoretic part
The preparation of 2.1 acrylamide gels
The concentration of glue needed for being determined according to molecular weight of albumen to be separated.Sequentially add high purity water in small beaker, 12
Sodium alkyl sulfate (SDS), acrylamide, Tris-Base (separation gel is pH 8.8, and concentration glue is pH 6.8) are mixed, are added rapidly
Enter sodium peroxydisulfate (AP), tetramethylethylenediamine (TEMED), mixes, be rapidly added between glass plate, isopropanol fluid-tight.To 30min glue
After solidification, concentration glue (Tris-Base, pH 6.8) is configured by said sequence, cleared fluid-tight water pours into concentration glue to its spilling glass
Glass plate, it is careful to be inserted into point sample comb, if any gap, glue, to its solidification.
2.2 electrophoresis
One clear interface of formation between meeting and separation gel, offset plate is removed, glass plate is put into after concentration gelling is solid, make electrode,
Glue constitutes circuit.Glue, electrode are put into electrolytic cell, electrolytic cell is put into electrophoresis cartridge.1 × electrophoretic buffer is poured into inside groove
To spilling, outer groove electrophoresis liquid level is made to be higher than the platinum filament of inside groove.It is careful to extract point sample comb, make electrophoretic buffer full of each point sample
Hole.By ready sample and protein Marker, it is successively carefully added into each loading wells.The lid of electrophoresis tank is covered.60V
Electrophoresis 30min or so then uses 120V electrophoresis 90min until bromophenol blue, which is compressed into filament, enters separation gel, when bromophenol blue (about
Stop electrophoresis when 10kDa) reaching glue bottom.
2.3 electricity turn
Offset plate is taken out, careful to open, part below excision concentration glue and bromophenol blue is taken measurements, corner cut makes marks, and is placed in electricity
Turn in buffer, impregnates 15min.Electricity turns sponge, filter paper used, and also electricity consumption turns buffer immersion 15min.According to the size of glue, cut
Take pvdf membrane.Successively methanol 15s, MilliQ water 2min is used to be put in electricity and turn to impregnate 15-60min in buffer.Pay attention to catching up with bubble,
Shut clip.It is inserted into electric turn trough, ready ice chest is put, is placed in outer groove, pour into electricity and turn liquid, close the lid.Albumen bear
Electricity makes albumen from the film that the glue of low potential is transferred to high potential.Electricity turns time 90min, voltage 70V.
2.4 immunoblotting
After electricity turns, clip is opened, pvdf membrane is placed on shaking table, be successively dipped in 10s in methanol, qualitative filter paper is dry
Whether 15min, methanol 10s, Ponceaux dye 2-5min, wash bands visible, turn to succeed as intermediate detection electricity.According to pre-dyed
Protein marker cut film, mark, TBS/T is washed 3 times, each 5min.By film as in confining liquid, shaking at room temperature
1h is shaken on bed.Film is placed in corresponding primary antibody dilution, shakes 1h at room temperature, overnight in 4 DEG C.Film washes 3 times with TBS/T, every time
5min.Later, film is placed in secondary antibody diluent, is incubated at room temperature 1h.Secondary antibody is abandoned, film is washed 3 times with TBS/T, each 5min.
2.5 analysis
Film is clapped using Dual band IR laser imaging system (Odyssey Infrared Imaging, LI-COR)
It takes the photograph, and analyzes slice result with software I mageJ software.
As a result see Fig. 2, show 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one chemical combination
Object causes CYP1A1 expressing quantity to raise.
Claims (1)
1.2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one is preparing aryl hydrocarbon receptor excitement
It is applied in the drug of agent, wherein the 2- (4- trifluoromethyl phenyl imido) -5- (2- naphthalenyhnethylene) thiazolidin-4-one is referred to as
TNTO, chemical structure is as shown in logical formula (I):
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| Title |
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| Design, Synthesis, Cytoselective Toxicity, Structure–Activity Relationships, and Pharmacophore of Thiazolidinone Derivatives Targeting Drug-Resistant Lung Cancer Cells;Hongyu Zhou et al.;《J. Med. Chem.》;20080208;第51卷;1242-1251 * |
| Syntheses and evaluation of 2,5-disubstituted 4-thiazolidinone analogues as antimicrobial agents;Pooja Chawla et al.;《Med Chem Res》;20120710;第21卷;2064-2071 * |
| 以芳香烃受体为药物靶点的肿瘤治疗研究;刘颖等;《中国药理学通报》;20160531;第32卷(第5期);607-612 * |
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