CN113288899B - Application of heterocyclic thiol compound in preparation of antitumor drugs - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
- C07D251/52—Two nitrogen atoms with an oxygen or sulfur atom attached to the third ring carbon atom
Abstract
The heterocyclic thiol compound provided by the invention shows better activity against liver cancer cells, human breast cancer cells or human non-small cell lung cancer cells, lays a foundation for screening and developing new drugs, and has better practical value.
Description
(I) technical field
The invention relates to an application of heterocyclic thiol compounds in preparing antitumor drugs.
(II) background of the invention
Malignant tumor is one of common diseases seriously threatening human health and all diseases, so the development of novel anti-tumor drugs has important practical significance. The heterocyclic ring is the basic mother nucleus of medicaments and natural products, and a large number of documents report that the compound has better biological activity, so that the further research on the application of heterocyclic thiol compounds in preparing antitumor medicaments has certain social significance.
Disclosure of the invention
In order to obtain an active component of a novel antitumor drug, the invention adopts the following technical scheme:
the application of heterocyclic thiol compounds shown as formula (I), (II) or (III) in preparing antitumor drugs is disclosed:
in the formula (I), R 1 、R 2 Each independently is C 1 ～C 10 Alkyl or R 1 And R 2 Are connected into a ring and combined with N between the two to form C containing N or N, O 4 ～C 8 A heterocycle; r is 3 、R 4 Each independently is C 1 ～C 10 Alkyl or R 3 And R 4 Are connected into a ring and are combined with N between the two to form C containing N or N, O 4 ～C 8 A heterocycle; preferably R 1 、R 2 Each independently is methyl or R 1 And R 2 Are connected to form a ring and are combined with N between the two to form a piperidine ring, a pyrrolidine ring or a morpholine ring; r 3 、R 4 Each independently is methyl or R 3 And R 4 Are connected into a ring and are combined with N between the two to formA piperidine ring, a tetrahydropyrrole or a morpholine ring;
in the formula (II), R 5 Is C 1 ～C 10 Alkyl or two R 5 Are connected into a ring and are combined with N between the two to form C containing N 4 ～C 8 A heterocycle; preferably R 5 Is methyl or two R 5 Are connected to form a ring and are combined with N between the two to form a piperidine ring;
in the formula (III), R 6 Is C 6 ～C 8 Aryl, preferably phenyl.
Further, the heterocyclic thiol compound is preferably one of the following compounds:
furthermore, the tumor cell is human liver cancer cell (HEPG 2), human breast cancer cell (T47D) or human non-small cell lung cancer cell (A549).
Furthermore, when the tumor is human liver cancer cell (HEPG 2), the compound (I-1) or (II-2) has better anti-tumor activity; when the tumor is a human breast cancer cell (T47D), the compound (II-1), (II-2) or (III-1) has better anti-tumor activity; when the tumor is human non-small cell lung cancer cell (A549), the compound (I-6), (II-1) or (III-1) has better anti-tumor activity.
The invention relates to a preparation method of heterocyclic thiol compounds shown in formula (I), which mainly comprises the steps of preparing 2-chloro-1,3,5-triazine intermediate shown in formula (IV) under the condition of room temperature by using cyanuric chloride and secondary amine (dimethylamine, piperidine, tetrahydropyrrole or morpholine) under the action of triethylamine, then reacting the intermediate with thiourea at 110 ℃, and treating with sodium hydroxide to obtain the heterocyclic thiol compounds shown in formula (I). Wherein the ratio of the amounts of substances of cyanuric chloride to secondary amine is 1:1 to 2:1; the mass ratio of the 2-chloro-1,3,5-triazine intermediate, thiourea and sodium hydroxide shown in formula (IV) is 1:2:1.
r in the formula (IV) 1 、R 2 、R 3 、R 4 Respectively with R in the formula (I) 1 、R 2 、R 3 、R 4 The same is true.
The invention relates to a preparation method of heterocyclic mercaptan compound shown in formula (II), which is mainly characterized in that dicyandiamide sodium and amine react at 90 ℃ in the presence of hydrochloric acid to obtain cyanoguanidine shown in formula (V); then reacting with sodium thiosulfate at room temperature under the action of hydrochloric acid to obtain guanyl thiourea shown in a formula (VI); finally, condensing with methyl formate under the action of sodium methoxide to obtain the heterocyclic mercaptan compound shown in the formula (II). Wherein the mass ratio of the amine to the substances of dicyandiamide sodium and hydrochloric acid is 1:1:1; the mass ratio of aniline, hydrochloric acid and sodium thiosulfate is 1:1.8:0.9; the mass ratio of guanylthiourea, sodium and ethyl formate is 1:3:4
R in the formulae (V), (VI) 5 And R in the formula (II) 5 The same is true.
The invention relates to a preparation method of a heterocyclic mercaptan compound shown in a formula (III), which is mainly characterized in that arylformyl isothiocyanate shown in a formula (VII) and arylformamidine shown in a formula (VIII) react at room temperature under the action of sodium hydroxide to prepare the heterocyclic mercaptan compound shown in the formula (III). Wherein, the mass ratio of the arylformyl isothiocyanate to the arylformamidine and the sodium hydroxide is 1:1:4;
r in the formulae (VII), (VIII) 6 And R in the formula (III) 6 The same is true.
Compared with the prior art, the invention has the beneficial effects that: the heterocyclic thiol compound provided by the invention shows better activity against liver cancer cells, human breast cancer cells (T47D) or human non-small cell lung cancer cells, lays a foundation for screening and developing new drugs, and has better practical value.
Detailed Description
The invention will now be further illustrated by the following examples, without limiting the scope of the invention thereto.
Example 1: preparation of Compound (I-1)
Cyanuric chloride (5.00g, 27.11mmol) was added to acetone (50 mL), morpholine (4.7mL, 53.94mmol) and triethylamine (11.2mL, 80.54mmol) were added under ice bath conditions, and the mixture was reacted at room temperature for 2 hours, after the reaction was completed, an appropriate amount of ice water was added, filtered, and dried to give compound (IV-1) (6.90 g).
The above-mentioned compound (IV-1) (6.90 g, the theoretical amount being 24.18 mmol) and thiourea (3.78g, 49.65mmol) were added to dioxane (50 mL) and reacted at 110 ℃ for 13 hours, the reaction solution was cooled to room temperature, filtered, the cake was dissolved in ethyl acetate (60 mL), and sodium hydroxide (1.0g, 25mmol) was further added to react at room temperature for 3 hours. After completion of the reaction, the reaction mixture was filtered, and the filter cake was washed with ethyl acetate and recrystallized from methanol to obtain compound (I-1) (3.51g, yield. 1 H NMR(500MHz,DMSO-d6)δ11.42(m,1H),3.81-3.65(m,8H),3.62-3.59(m,8H)。
Example 2: preparation of Compound (I-2)
The same procedure as in example 1 was repeated except that morpholine was changed to piperidine (1.8mL, 18.18mmol), the amount of cyanuric chloride was changed to (1.78g, 9.65mmol), the amount of triethylamine was changed to (4.7mL, 33.81mmol), compound (IV-1) was changed to compound (IV-2) (1.73g, 6.14mmol), and the amount of thiourea was changed to (1.03g, 13.53mmol), whereby compound (I-2) (0.57g, yield. 1 H NMR(500MHz,DMSO-d6)δ11.42(m,1H),3.81-3.65(m,8H),3.62-3.59(m,8H)。
Example 3: preparation of Compound (I-3)
The same operation as in example 1 was carried out except that morpholine was changed to dimethylamine aqueous solution (10mL, 60.20mmol), the amount of cyanuric chloride was changed to (5.56g, 30.15mmol), the amount of triethylamine was changed to (13mL, 93.92mmol), the amount of compound (IV-1) was changed to compound (IV-3) (5.21g, 25.91mmol), and the amount of thiourea was changed to (3.95g, 51.86mmol), whereby compound (I-3) (3.62g, yield
Example 4: preparation of Compound (I-4)
The same procedure as in example 1 was repeated except that the amount of morpholine was changed to (1.4 mL, 16.26mmol), the amount of cyanuric chloride was changed to (2.98g, 16.26mmol), and the amount of triethylamine was changed to (7.0 mL, 50.26mmol), to give compound (VII-1) (2.36 g); the same operation as in example 1 was carried out except that morpholine was changed to tetrahydropyrrole (0.8mL, 10.00mmol), cyanuric chloride was changed to compound (VII-1) (2.36g, 10mmol), the amount of triethylamine was changed to (4.2mL, 30.00mmol), compound (IV-1) was changed to compound (IV-4) (1.01g, 3.74mmol), and the amount of thiourea was changed to (0.58g, 7.62mmol), so as to obtain compound (I-4) (0.39g, yield; 1 H NMR(500MHz,DMSO-d6)δ11.27(s,1H),3.79-3.67(m,4H),3.63-3.58(m,4H),3.51-3.44(m,4H)。
example 5: preparation of Compound (I-5)
The same operation as in example 4 was carried out except that morpholine was changed to piperidine (3.0 mL, 30.30mmol), the amount of cyanuric chloride was changed to (6.00g, 32.54mmol), and the amount of triethylamine was changed to (15.0 mL, 107.92mmol), to give compound (VII-2) (3.38 g); the same procedure as in example 1 was repeated, except that the amount of morpholine was changed to (1.3 mL, 14.92mmol), the amount of cyanuric chloride was changed to compound (VII-2) (3.38g, 14.50mmol), the amount of triethylamine was changed to (6.1 mL, 43.86mmol), the amount of compound (IV-4) was changed to compound (IV-5) (3.2 g, 11.28mmol), and the amount of thiourea was changed to (1.77g, 23.25mmol), to obtain compound (I-5) (1.49g, yield; 1 H NMR(500MHz,DMSO-d6)δ11.14(s,1H),3.84–3.60(m,4H),3.52–3.40(m,4H),1.96–1.76(m,4H),1.65–1.56(m,2H),1.52–1.42(m,4H)。
example 6: preparation of Compound (I-6)
The same operation as in example 5 was conducted except that the amount of compound (VII-2) was changed to (2.81g, 12.05mmol), morpholine was changed to tetrahydropyrrole (1.0mL, 12.05mmol), the amount of triethylamine was changed to (5.4mL, 38.85mmol), compound (IV-5) was changed to compound (IV-6) (1.99g, 7.40mmol), and the amount of thiourea was changed to (1.13g, 14.80mmol), whereby compound (I-6) (1.43g, yield; 1 H NMR(500MHz,DMSO-d6)δ11.15(s,1H),3.76–3.66(m,4H),3.51–3.42(m,4H),1.95–1.79(m,4H),1.65–1.58(m,2H),1.53–1.44(m,4H)
example 7: preparation of Compound (II-1)
Dimethylamine hydrochloride (10.00g, 122.64mmol) was added to water (60 mL), sodium dicyandiamide (12.00g, 134.90mmol) was added, and the mixture was heated to 90 ℃ for reaction for 34h. The reaction solution was cooled to room temperature, filtered, and the filter cake was washed with water and dried to obtain compound (V-1).
Adding the compound (V-1) into acetone (75 mL), respectively adding concentrated hydrochloric acid 12mL and 144mmol and sodium thiosulfate pentahydrate (16.00g and 82.35mmol), reacting at room temperature for 2h, adjusting pH to =9 with ammonia water after the reaction is finished, concentrating, and performing column chromatography (eluent is dichloromethane: methanol =40, volume ratio) to give compound (VI-1) (7.65 g).
Adding sodium (1.06g, 43.48mmol) into methanol (25 mL), completely dissolving sodium, adding above compound (VI-1) (2.52g, 17.24mmol), reacting at room temperature for 3h, adding ethyl formate (4.5mL, 75.69mmol), reacting at room temperature for 21h, concentrating the reaction solution after reaction, adding water, extracting with dichloromethane for 3 times, combining organic layers, drying with anhydrous sodium sulfate, filtering, concentrating the filtrate, and performing column chromatography (the eluent is dichloromethane: methanol =)40, volume ratio) to give compound (II-1) (1.41g, 53%). 1 H NMR(500MHz,DMSO-d6)δ12.90(s,1H),8.07(s,1H),3.16(s,3H),3.13(s,3H)。
Example 8: preparation of Compound (II-2)
The same operation as in example 8 was conducted except that dimethylamine hydrochloride was changed to piperidine (10.00g, 117.43mmol) and dilute hydrochloric acid (117.43mL, 117.43mmol), and the amount of sodium dicyandiamide was changed to (10.5g, 117.94mmol), giving compound (V-2).
The amount of concentrated hydrochloric acid was changed to (5mL, 60mmol) and the amount of sodium thiosulfate pentahydrate was changed to (5.50g, 28.31mmol), giving compound (VI-2) (3.75 g)
The amount of sodium was changed to (0.50g, 21.73mmol), the amount of compound (VI-1) was changed to compound (VI-2) (1.50g, 8.05mmol), and the amount of methyl formate was changed to (2.0mL, 32.20mmol), whereby compound (II-2) (1.38g, 87%) was obtained. 1 H NMR(500MHz,DMSO-d6)δ12.85(s,1H),8.06(s,1H),3.80–3.76(m,4H),1.66–1.61(m,2H),1.56–1.51(m,4H)
Example 9: preparation of Compound (III-1)
To a solution of benzamidine hydrochloride (0.48g, 3.06mmol) in toluene (4 mL) and water (8 mL) was added a solution of sodium hydroxide (0.49g, 12.25mmol) in water (3 mL), followed by addition of benzoyl isothiocyanate (0.4 mL, 3.06mmol), reaction at room temperature for 30 minutes, adjustment of the reaction solution PH to 6 with hydrochloric acid, addition of water, extraction with ethyl acetate 3 times, combination of organic layers, drying over anhydrous sodium sulfate, filtration, concentration, column chromatography (eluent: dichloromethane: methanol =40, volume ratio: 1) to obtain compound (III-1) (0.41g, 51%). 1 HNMR(500MHz,DMSO-d6)δ14.40(s,1H),8.45–8.41(m,4H),7.75–7.71(m,2H),7.65–7.60(m,4H)
Example 10: biological activity test of human liver cancer cell (HEPG 2), human breast cancer cell (T47D) or human non-small cell lung cancer cell (A549)
An in vitro anti-human liver cancer cell (HEPG 2), human breast cancer cell (T47D) or human non-small cell lung cancer cell (A549) activity test method comprises the following steps: MTT method
The experimental steps are as follows:
1) Preparation of samples: for soluble samples, each 1mg was dissolved in 20. Mu.L DMSO, 2. Mu.L was diluted with 1000. Mu.L of culture medium to a concentration of 100. Mu.g/mL, and then the culture medium was serially diluted to the use concentration.
2) Culture of cells
2.1 Preparation of culture medium, each 1000mL of culture medium contains 80 million units of penicillin, 1.0g of streptomycin and 10% inactivated fetal calf serum.
2.2 Culture of cells): inoculating the tumor cells into the culture medium, placing at 37 deg.C, 5% 2 Culturing in an incubator, and carrying out passage for 3-5 days.
3) Determination of the inhibition of tumor cell growth by samples
The cells were digested with EDTA-pancreatin digest and diluted to 1X 10 with medium 5 Perml, added to a 96-well cell culture plate at 100uL per well, 37 ℃,5% CO 2 Culturing in an incubator. 24h after inoculation, adding the medium diluted sample, 100. Mu.L per well, 3 wells per concentration, 37 ℃,5% 2 The culture in the incubator, after 72h, adds 5mg/mL MTT to the cell culture wells, 10. Mu.L per well, incubate at 37 ℃ for 4h, add DMSO, 150. Mu.L per well, shake with a shaker, completely solubilize the formazan, and color with a microplate reader at a wavelength of 570 nm. The tumor cell inhibition rate of the samples was calculated by using cells cultured in the medium containing no sample and the same concentration of DMSO as a control under the same conditions, and the results are shown in Table 1.
The inhibition effect of 9 samples of the compounds (I-1) - (I-6), (II-1) - (II-2) and (III-1) on the growth of liver cancer cells, human breast cancer cells or non-small cell lung cancer cells in vitro was determined by taking human liver cancer cells (HEPG 2), human breast cancer cells (T47D) or human non-small cell lung cancer cells (A549) as models (the results are detailed in Table 1).
TABLE 1.60. Mu. Mol/L inhibition ratio (%) (for human hepatoma cells (HEPG 2), human breast cancer cells (T47D) or human non-small cell lung cancer cells (A549) of each compound
| Compound (I) | HEPG2 | T47D | A549 |
| (I-1) | 71.17 | 29.01 | <10 |
| (I-2) | <10 | 24.61 | 31.73 |
| (I-3) | <10 | 69.80 | 19.06 |
| (I-4) | 11.93 | 34.60 | 65.06 |
| (I-5) | <10 | 19.35 | 36.85 |
| (I-6) | 24.36 | 20.26 | 21.57 |
| (II-1) | 11.30 | 30.45 | 50.24 |
| (II-2) | 60.66 | 79.73 | 25.77 |
| (III-1) | <10 | 60.73 | 85.68 |
Claims (12)
1. The application of heterocyclic thiol compounds shown as formula (I), (II) or (III) in preparing antitumor drugs is disclosed:
in the formula (I), R 1 、R 2 Each independently is C 1 ～C 10 Alkyl or R 1 And R 2 Are connected into a ring and are combined with N between the two to form C containing N or N, O 4 ～C 8 A heterocycle; r 3 、R 4 Each independently is C 1 ～C 10 Alkyl or R 3 And R 4 Are connected into a ring and are combined with N between the two to form C containing N or N, O 4 ～C 8 A heterocycle;
in the formula (II), R 5 Is C 1 ～C 10 Alkyl or two R 5 Are connected into a ring and are combined with N between the two to form C containing N 4 ～C 8 A heterocycle;
in the formula (III), R 6 Is C 6 ～C 8 An aryl group; the tumor is human breast cancer cell.
2. The use of a heterocyclic thiol compound of formula (I) according to claim 1 in the preparation of an anti-tumor medicament, wherein:
R 1 、R 2 each independently is methyl or R 1 And R 2 Are connected to form a ring and are combined with N between the two to form a piperidine ring, a pyrrolidine ring or a morpholine ring; r 3 、R 4 Each independently is methyl or R 3 And R 4 Linked to form a ring and combined with the N between the two to form a piperidine ring, a tetrahydropyrrole or a morpholine ring.
3. The use of a heterocyclic thiol compound of formula (II) according to claim 1 in the preparation of an anti-tumor medicament, wherein: r 5 Is methyl or two R 5 Are connected to form a ring and are combined with N between the two to form a piperidine ring.
4. The use of a heterocyclic thiol compound of formula (III) according to claim 1 in the preparation of an anti-tumor medicament, wherein: r 6 Is phenyl.
5. The use of a heterocyclic thiol compound of formula (I), (II) or (III) as defined in claim 1 in the preparation of an anti-tumor medicament, wherein:
the heterocyclic thiol compound is one of the following compounds:
6. use of the heterocyclic thiol compounds of formula (I), (II) or (III) according to claim 1 in the preparation of antitumor drugs, wherein: the tumor is T47D cell.
7. Use of the heterocyclic thiol compounds of formula (I), (II) or (III) according to claim 6 for the preparation of antitumor drugs, characterized in that: the heterocyclic thiol compound is (II-1), (II-2) or (III-1).
8. The application of the heterocyclic thiol compound in preparing the antitumor drugs is characterized in that the heterocyclic thiol compound is one of the following compounds:
9. The use of claim 8, wherein: the tumor is HEPG2 cell.
10. The application of the heterocyclic thiol compound in preparing the antitumor drugs is characterized in that the heterocyclic thiol compound is one of the following compounds:
11. The use of claim 10, wherein: the tumor is A549 cells.
12. The use of claim 11, wherein: the heterocyclic thiol compound is (I-6), (II-1) or (III-1).
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Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9219776D0 (en) * | 1992-09-18 | 1992-10-28 | Inst Of Cancer The Research | New compounds for use in the treatment of cancer |
| US6262053B1 (en) * | 1999-06-23 | 2001-07-17 | Parker Hughes Institute | Melamine derivatives as potent anti-cancer agents |
| AU2004212421B2 (en) * | 2003-02-07 | 2009-08-20 | Vertex Pharmaceuticals Incorporated | Heteroaryl substituted pyrolls useful as inhibitors of protein kinases |
| AU2014200528B2 (en) * | 2006-12-15 | 2016-05-12 | Nantbio, Inc. | Triazine derivatives and their therapeutical applications |
| CN103582482B (en) * | 2011-03-02 | 2016-10-12 | 利德探索中心有限公司 | Dibasic pyrrolotriazine derivatives of pharmaceutical active |
| CN102267983B (en) * | 2011-06-16 | 2013-06-12 | 台州职业技术学院 | Sym-triazine derivative compounds containing sym-tetrazine rings and preparation method thereof |
| CN102659765B (en) * | 2011-12-31 | 2014-09-10 | 沈阳药科大学 | Pyrimidine and triazine compound preparation method and application |
| KR101472083B1 (en) * | 2012-10-22 | 2014-12-16 | 광주과학기술원 | Pharmaceutical Compositions for Preventing or Treating Cancers Comprising ENOblock as an Active Ingredient |
| US10266517B2 (en) * | 2014-12-23 | 2019-04-23 | Dana-Farber Cancer Institute, Inc. | Pyrimidines as EGFR inhibitors and methods of treating disorders |
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