CN101786976A - Selenium thioxo cysteine benzamide compound and preparation method and application thereof - Google Patents
Selenium thioxo cysteine benzamide compound and preparation method and application thereof Download PDFInfo
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- CN101786976A CN101786976A CN200910077604A CN200910077604A CN101786976A CN 101786976 A CN101786976 A CN 101786976A CN 200910077604 A CN200910077604 A CN 200910077604A CN 200910077604 A CN200910077604 A CN 200910077604A CN 101786976 A CN101786976 A CN 101786976A
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Abstract
The invention discloses a selenium thioxo cysteine benzamide compound and a pharmaceutically acceptable salt thereof. Compared with the dissolvability of ethaselen and derivatives thereof, the dissolvability of the selenium thioxo cysteine benzamide compound is improved, thus the selenium thioxo cysteine benzamide compound has excellent anti-tumor effect and more wide medicinal application.
Description
Technical field
The present invention relates to a kind of novel organic selenium compounds, particularly selenium thioxo cysteine benzamide compound and preparation method thereof and its application.
Background technology
CN1166651C, CN1281593C, CN1242999C, CN1280279A, CN1704408A, CN1704409A, CN1704410A, CN1853627A and CN1990475A disclose " having the two or different selenazoles substitution compound of sugared phenylpropyl alcohol of anti-inflammatory and antitumor action R-" respectively, " immunomodulatory of benzisoxa selenazoles derivative and biotherapy effect ", " benzisoxa selenazoles derivative and application thereof ", " two benzisoxa sulfinpyrazone compounds and synthetic and application thereof ", " different selenazoles ketone compounds and its title complex and application thereof ", " have anti-fibrosis and suppress active compound of gelatinase and application thereof ", " Benzisoelenazolone derivative and preparation method thereof and application ", " bibenziisosehenazoleethane ethane cyclodextrin or cyclodextrin derivant clathrate and preparation method thereof and its purposes ", " replace benzisoxa selenazoles ketone compounds and uses thereof ".These applications or patent all disclose have anti-tumor activity, immunomodulatory and biotherapy activity, anti-fibrosis and suppress the active 2-phenyl-1 of gelatinase, 2-benzisoxa selenazoles-3 (2)-ketone ethane (calling " ethane selenium quinoline " in the following text) and derivative thereof, but the solvability of these organic selenium compounds is bad, has limited its medicinal use and range of application.Therefore, the solvability of improving these organic selenium compounds becomes the problem that people press for solution.The disclosed content of aforementioned application or patent is all as the application's reference.
Summary of the invention
The object of the present invention is to provide a kind of better deliquescent selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt, described compound has following formula I and the described structure of formula II:
Wherein:
R1 is C
1-12Alkylidene group, phenylene, biphenylene, inferior triphenyl, inferior hexanaphthene, pentamethylene ,-R
aSSR
a-,-(R
aO)
nR
a-,-(CH
2) (R
aO)
3R
a-,-R
aN (CH
3)
2R
a-or-R
aNHR
a-;
R1, R3 independently are hydrogen, halogen, itrile group, C separately
1-C
6Alkyl, C
1-C
6Alkoxyl group, C
1-C
6Alkylthio, N (C
1-C
6Alkyl)
2, NH (C
1-C
6Alkyl), COOH ,-COR
b, CONHR
b, CONR
cR
d, SO
3R, aryl, heteroaryl, cycloalkyl, heterocyclic radical, described group can be chosen wantonly by C
1-C
6Alkyl, C
1-C
6Alkoxyl group, halogen, itrile group, aryl, heteroaryl replace, and wherein R1, R3 can not be zero simultaneously;
R
aBe C
1-6Alkylidene group; R
bBe H, C
1-C
6Alkyl, C
1-C
6Alkoxyl group; R
c, R
dIndependently be selected from H, C
1-C
6Alkyl or phenyl, or R
c, R
dForm nitrogen heterocyclic ring or nitrogenous hetero-aromatic ring with the N that is connected;
N is 0-4.
Further, the mol ratio of selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt and halfcystine is 1: 1 or 1: 2 in the described compound.
Further, the present invention preferably protects selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt of following structure:
1) 1,2[two (2-selenium thioxo cysteine benzamide)] ethane
2) 3-[(2-(N-(benzisoxa selenazoles 3 (2H) ketone) ethyl formyl ammonia) benzene selenium sulfydryl]-the 2-alanine
For clear statement protection scope of the present invention, the contriver is defined as follows following groups:
" C1-C6 alkyl " comprises the straight or branched low alkyl group with 1～6 carbon atom, for example methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, amyl group, tert-pentyl or hexyl etc.
" C1-C6 alkoxyl group " comprises methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, isobutoxy, tert.-butoxy, pentyloxy, uncle's pentyloxy or hexyloxy etc.
" C1-C12 alkylidene group " comprises the straight-chain alkyl-sub-with 1～12 carbon atom, is preferably the alkylidene group of 1-6 carbon atom, for example, and methylene radical, ethylidene, trimethylene, tetramethylene, pentamethylene or hexamethylene.
" phenylene, biphenylene, inferior triphenyl ", " inferior hexanaphthene, inferior pentamethylene " are meant the substituting group that contains two connecting keys, such as, phenylene comprises 1,2-phenylene, 1,3-phenylene, 1, the 4-phenylene, inferior hexanaphthene comprises 1,2-hexylidene, 1,3-hexylidene, 1, the 4-hexylidene, cyclopentylidene comprises 1,2-cyclopentyl or 1, the 3-cyclopentyl.
" aryl " comprises phenyl, naphthyl etc., and described aryl can have one or more (preferably 1～3) suitable substituents, for example halogen, itrile group, amino, C1-6 alkyl, C1-C6 alkoxyl group, list (or two or three) halos (rudimentary) alkyl etc.
Described " heteroaryl " be meant heteroatomic 5-unit's aromatic ring of comprising 1,2,3 or 4 such as nitrogen, oxygen or sulphur or 6 yuan of aromatic rings and with this class ring of aryl rings, cycloalkyl ring, heteroaryl ring or heterocycloalkyl ring condensed (for example benzothienyl, indyl), and comprise possible N-oxide compound.Described heteroaryl can be chosen wantonly and comprise that 1-4 substituting group, suitable substituents are selected from for example substituting groups such as halogen, itrile group, amino, C1-6 alkyl, C1-C6 alkoxyl group, list (or two or three) halos (rudimentary) alkyl;
" cycloalkyl " is meant 4-unit, 5-unit, the saturated or undersaturated carbocyclic ring of part of 6-unit or 7-unit, and described ring can be by for example replacements such as halogen, itrile group, amino, C1-6 alkyl, C1-C6 alkoxyl group, list (or two or three) halos (rudimentary) alkyl of suitable substituents.
" Heterocyclylalkyl " or " heterocycle " is meant 4-unit, 5-unit, the saturated or undersaturated ring of part of 6-unit or 7-unit, comprises 1-2 the heteroatoms such as nitrogen, oxygen and/or sulphur.Can have one or more (preferably 1～3) suitable substituents, for example, halogen, itrile group, amino, C1-6 alkyl, C1-C6 alkoxyl group, list (or two or three) halos (rudimentary) alkyl etc.
So-called " nitrogenous " heterocycle or hetero-aromatic ring refer to contain at least the ring of a N.
Described pharmaceutically acceptable salt comprises its inorganic acid addition salt, organic acid adduct, mineral alkali adduct or organic bases adduct, for example, hydrochloride, hydrobromate, hydriodate, vitriol, nitrate, tosilate, mesylate, phosphoric acid salt, vitriol, perchlorate, acetate, trifluoroacetate, propionic salt, citrate, malonate, succinate, lactic acid salt, oxalate, tartrate, benzoate, magnesium salts or calcium salt, alkylbenzyldimethylasaltsum saltsum, piperidinium salt, trialkyl amine salt, pyridinium salt, dimethylamine salt or diethyl amine salt.
Selenium thioxo cysteine benzamide compound of the present invention or its pharmacy acceptable salt have following advantage:
1, the freeze-drying prods of this compounds is water-soluble good, and character is more stable.Measure through HPLC, the dried frozen aquatic products of this compounds contains the ethane selenium quinoline of solubility up to 8.87%, and solubleness can reach more than the 1.2mg/ml;
2, the stabilized aqueous solution of this compounds, and its content of dispersion obviously is better than the HP-beta-CD inclusion of ethane selenium quinoline and derivative thereof.
Another object of the present invention is to provide a kind of composition, described composition is made up of the selenium thioxo cysteine benzamide compound of structure shown in above-mentioned logical formula I or (II) or its pharmacy acceptable salt and halfcystine.
Further, the mol ratio of the selenium thioxo cysteine benzamide compound of structure or its pharmacy acceptable salt and halfcystine is 1 shown in described composition formula of (I) or (II): 1-1: 10, be preferably 1: 2-1: 8, more preferably 1: 3-1: 6, most preferably be 1: 4-1: 5.
Foregoing can improve the selenium thioxo cysteine benzamide compound of structure shown in logical formula I or (II) or the solvability and the drug effect (antitumous effect) of its pharmacy acceptable salt, and the two combination has synergistic function.
Another object of the present invention is to provide a kind of above-mentioned logical formula I of preparation or the selenium thioxo cysteine benzamide compound of (II) or the method for its pharmacy acceptable salt, comprise the steps:
1) ethane selenium quinoline compounds is wetting with ethanol, ultra-sonic dispersion;
2) with 0.242g-halfcystine 5ml water dissolution;
3) under the agitation condition, with 1) the ethane selenium quinoline compounds ethanolic soln of step gained adds 2) in the L-halfcystine aqueous solution of step gained, mix, regulate pH value to alkalescence with the aqueous sodium hydroxide solution of 1M, after dissolving fully, drying, promptly.
Another object of the present invention is to provide a kind of pharmaceutical composition, said composition is made up of acceptable carrier on the selenium thioxo cysteine benzamide compound of above-mentioned logical formula I or (II) or its pharmacy acceptable salt, halfcystine and the pharmacology.
Further, the mol ratio of the selenium thioxo cysteine benzamide compound of structure or its pharmacy acceptable salt and halfcystine is 1 shown in composition formula of (I) or (II): 1-1: 10, be preferably 1: 2-1: 8, more preferably 1: 3-1: 6, most preferably be 1: 4-1: 5.
Further, selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt in the composition: the weight ratio of auxiliary material is 0.001-99: 1-99, be preferably 0.001-90: 1-95, more preferably 0.001-80: 1-90 most preferably is 0.001-70: 1-85.
Further, the weight percentage of selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt is 1-99% in the composition, is preferably 5-95%, also is preferably 10-90%, and more preferably 15-85% most preferably is 20-80%.
Composition of the present invention can be various formulation well known in the art.Be suitable for formulation of the present invention and can be oral preparations, external preparation or injection, be preferably oral preparations or injection.Described oral preparations is selected from inclusion preparation, dispersion agent, oral liquid, tablet, capsule, granule, dripping pill, pill, powder, syrup, mixture, distillate medicinal water, suspension agent, effervescent, paste, suspension, emulsion or medicinal tea; Be preferably inclusion preparation or dispersion agent; Preferred described suspension agent is selected from does outstanding agent or suspension; Described external preparation is selected from gelifying agent, paste, emplastrum, plaster, creme, ointment, liniment, lotion, suppository, basting agent or coagulates paste; Described injection is selected from injection (injection liquid), transfusion or freeze-dried powder etc.Can adopt preparation technique means well known in the art to prepare composition of the present invention.
Described pharmaceutically acceptable carrier is well known usual excipients or the auxiliary material that is used to prepare above-mentioned preparation, and vehicle that oral preparations or external preparation are commonly used or auxiliary material include but are not limited to weighting agent (claim not only thinner), lubricant (but also claiming glidant or antitack agent), dispersion agent, wetting agent, tackiness agent, conditioning agent, solubilizing agent, oxidation inhibitor, fungistat, emulsifying agent, correctives or reodorant etc.Tackiness agent, for example syrup, gum arabic, gelatin, sorbyl alcohol, tragacanth, Mierocrystalline cellulose and derivative thereof, gelatine size, syrup, starch slurry or polyvinylpyrrolidone, preferred derivatived cellulose is Microcrystalline Cellulose, Xylo-Mucine, ethyl cellulose or HPMC; Weighting agent, for example lactose, Icing Sugar, dextrin, starch and derivative thereof, Mierocrystalline cellulose and derivative thereof, inorganic calcium salt, sorbyl alcohol or glycine, preferred inorganic calcium salt is calcium sulfate, calcium phosphate, secondary calcium phosphate or precipitated calcium carbonate; Lubricant, for example micropowder silica gel, Magnesium Stearate, talcum powder, aluminium hydroxide, boric acid, hydrogenated vegetable oil or polyoxyethylene glycol; Disintegrating agent, for example starch and derivative thereof, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone or Microcrystalline Cellulose, preferred starch derivative is sodium starch glycolate, Explotab, pregelatinized Starch, modified starch, hydroxypropylated starch or W-Gum; Wetting agent, for example sodium lauryl sulphate, water or alcohol etc.
Vehicle or auxiliary material that described injection is commonly used include but are not limited to: oxidation inhibitor, for example S-WAT, sodium bisulfite and Sodium Pyrosulfite; Fungistat, for example 0.5% phenol, 0.3% cresols, 0.5% trichloro-butyl alcohol; Acid-base modifier, for example hydrochloric acid, Citric Acid, potassium hydroxide, sodium hydroxide, Sodium Citrate and buffer reagent phosphoric acid salt and damping fluid thereof; Emulsifying agent, for example Tween-80, do not have that sour sorb is smooth, Pu Luonike F-68, lecithin, fabaceous lecithin; Solubilizing agent, for example tween-80, bile, glycerine etc.
In addition, also activeconstituents can be mixed by its preparation requirement with pharmaceutically acceptable slow controlled release carrier, again according to the preparation method of sustained-release preparation well known in the art, as adding the retarding agent dressing or with making micropill after the active principle microcapsulesization again, as sustained release pellet or controlled release micro pill; Described slow controlled release carrier includes but are not limited to oil agent, hydrophilic colloid or the dressing retarding agent etc. of mixing, described oil any or its combination that agent is selected from glyceryl monostearate, hydrogenated castor oil, Dormant oils, polysiloxane or dimethyl siloxane of mixing; Described hydrophilic colloid is selected from any or its combination of Xylo-Mucine, hydroxypropylcellulose, Vltra tears, PVP, gum arabic, tragcanth or carbopol; Described dressing retarding agent is selected from any or its combination of ethyl cellulose (EC), HPMC (HMPC), polyvinylpyrrolidone (PVP), cellulose acetate-phthalate (CAP), acrylic resin.
Another object of the present invention is to provide selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt or its composition to have application in the anti-tumor activity medicine in preparation, described tumour comprises solid tumor or leukemia, be preferably solid tumor, described solid tumor is selected from thyroid carcinoma, prostate cancer, colorectal carcinoma, the rectum cancer, melanoma, liver cancer, lung cancer, colorectal carcinoma, cancer of the stomach, carcinoma of submaxilary gland, nasopharyngeal carcinoma or mammary cancer, is preferably colorectal carcinoma, cancer of the stomach or carcinoma of submaxilary gland.
The dosage that selenium thioxo cysteine benzamide compound of the present invention or its pharmacy acceptable salt are used for the treatment of tumour is about the 0.05-250mg/Kg body weight, be preferably the 0.5-200mg/Kg body weight, more preferably the 2-100mg/Kg body weight most preferably is the 5-80mg/Kg body weight.The actual dosage of chemical compounds I and II can suitably be adjusted according to factors such as patient's the state of an illness, physique, body weight, age, sexes.
Description of drawings
Figure 11,2[two (2-selenium thioxo cysteine benzamide)] mass spectrum of ethane.
Embodiment
Specify the present invention below with reference to embodiment, embodiments of the invention only are used to technical scheme of the present invention is described, and non-limiting essence of the present invention.
Embodiment 11,2[two (2-selenium thioxo cysteine benzamide)] preparation of ethane
1) 100mg ethane selenium quinoline is wetting with 10ml ethanol, ultra-sonic dispersion;
2) with 0.28g-halfcystine 5ml water dissolution;
3) under the agitation condition, with 1) the ethane selenium quinoline ethanolic soln of step gained adds 2) the L-halfcystine of step gained, mix, regulate pH value to alkaline with the aqueous sodium hydroxide solution of 1M, it is dissolved fully, lyophilize or rotary evaporation, drying, promptly.
Gained 1,2[two (2-selenium thioxo cysteine benzamide)] ethane (calling " ethane selenium quinoline/CYS " in the following text) pH value of water solution is between 7.5-12, and its lyophilized products physiological saline solution shows and redissolves well, and the intravenous fluid of making stability is better.
The ESI mass spectrum of ethane selenium quinoline/CYS shows that the mol ratio of ethane selenium quinoline and cysteine cpd is 1: 2 (MW661)-1: 4 (MW900), and this mass spectrum shows, the mol ratio 1 of ethane selenium quinoline and halfcystine: 4-1: 10.
Measure through HPLC, ethane selenium quinoline/CYS contains solubility ethane selenium quinoline 8.87%, and promptly 11.275mg ethane selenium quinoline/CYS contains solubility ethane selenium quinoline 1mg.
Embodiment 2Ethane selenium quinoline/CYS is to the growth-inhibiting effect of mouse tumor cell
2.1 experimental technique
Body weight is 84 of the Male Kunming strain mice of 20 ± 2g, H22 liver cancer cell and physiological saline get its liver cancer cell suspension according to 1: 3 dilution proportion, behind the inoculated with subcutaneous injections liver cancer cell suspension 0.2ml of the right fore oxter of mouse, be divided into 7 groups at random, comprise ethane selenium quinoline/CYS intravenous injection group, ethane selenium quinoline/CYS abdominal injection group, oral ethane selenium quinoline/CYS high dose group, oral cavity instillation ethane selenium quinoline/CYS group, oral ethane selenium quinoline/CYS low dose group, oral ethane selenium quinoline suspension group and physiological saline group.24h begins according to the body weight administration from the inoculation back.
2.2 the administering mode and the dosage of each group of test
Ethane selenium quinoline/CYS intravenous injection group: take by weighing 78.925mg ethane selenium quinoline/CYS every day, add physiological saline 14ml, shake up, 0.45 μ m filter element filtering, concentration be the test solution of 0.5mg/ml, be administered once by the dosage tail vein injection of 2mg/kg body weight.
Ethane selenium quinoline/CYS abdominal injection group: take by weighing 78.925mg ethane selenium quinoline/CYS every day, add physiological saline 14ml, shake up, 0.45 μ m filter element filtering, concentration be the test solution of 0.5mg/ml, the dosage intraperitoneal injection of pressing the 10mg/kg body weight is once.
Oral ethane selenium quinoline/CYS high dose group: take by weighing 406mg ethane selenium quinoline/CYS every day, add physiological saline 18ml, shake up, concentration be the test solution of 2mg/ml, the dosage gastric infusion of pressing the 36mg/kg body weight is once.
Oral cavity instillation ethane selenium quinoline/CYS: take by weighing 203mg ethane selenium quinoline/CYS every day, add 900mgPEG-4000 and 450mg PVP-K30, add physiological saline 4ml, shake up, concentration be the test solution of 4mg/ml, press twice of the dosage oral cavity dropleting medicine-feeding of 18mg/kg body weight.
Oral ethane selenium quinoline/CYS low dosage: take by weighing 406mg ethane selenium quinoline/CYS every day, add physiological saline 18ml, shake up, concentration be the test solution of 2mg/ml, the dosage gastric infusion of pressing the 18mg/kg body weight is once.
Oral ethane selenium quinoline suspension group: take by weighing 720mg ethane selenium quinoline and 1g CMC-Na every day, add physiological saline 180ml, ultrasonic, be uniformly dispersed, concentration be the test solution of 4mg/ml, the dosage gastric infusion of pressing the 72mg/kg body weight is once.
The physiological saline group: irritate stomach according to the 18ml/kg body weight and give physiological saline every day.
Behind the successive administration 8 days, the sacrificed by decapitation mouse, blood sample collection in heparinization EP pipe, centrifugal separation plasma ,-20 ℃ frozen standby.Every mouse strips tumour, weighs, and calculates tumour inhibiting rate.
2.3 test-results
Afore-mentioned test the results are shown in Table 1.
Table 1 ethane selenium quinoline and ethane selenium quinoline/CYS are to H
22The tumour inhibiting rate of mice with tumor
Learnt by table 1: the intravenous injection group of ethane selenium quinoline/CYS, abdominal injection group are compared for oral group with ethane selenium quinoline, to H
22The tumor growth restraining effect of mice with tumor has significant difference.
Claims (10)
1. a selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt, described compound has following formula I and the described structure of formula II:
Wherein:
R1 is C
1-12Alkylidene group, phenylene, biphenylene, inferior triphenyl, inferior hexanaphthene, pentamethylene ,-R
aSS R
a-,-(R
aO)
nR
a-,-(CH
2) (R
aO)
3R
a-,-R
aN (CH
3)
2R
a-or-R
aNH R
a-;
R1, R3 independently are hydrogen, halogen, itrile group, C separately
1-C
6Alkyl, C
1-C
6Alkoxyl group, C
1-C
6Alkylthio, N (C
1-C
6Alkyl)
2, NH (C
1-C
6Alkyl), COOH ,-COR
b, CONHR
b, CONR
cR
d, SO
3R, aryl, heteroaryl, cycloalkyl, heterocyclic radical, described group can be chosen wantonly by C
1-C
6Alkyl, C
1-C
6Alkoxyl group, halogen, itrile group, aryl, heteroaryl replace, and wherein R1, R3 can not be zero simultaneously;
R
aBe C
1-6Alkylidene group; R
bBe H, C
1-C
6Alkyl, C
1-C
6Alkoxyl group; R
c, R
dIndependently be selected from H, C
1-C
6Alkyl or phenyl, or R
c, R
dForm nitrogen heterocyclic ring or nitrogenous hetero-aromatic ring with the N that is connected;
N is 0-4.
2. selenium thioxo cysteine benzamide compound according to claim 1, the mol ratio of selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt and halfcystine is 1: 1 or 1: 2 in the described compound.
3. selenium thioxo cysteine benzamide compound according to claim 1, described compound is selected from following structure:
1) 1,2[two (2-selenium thioxo cysteine benzamide)] ethane
2) 3-[(2-(N-(benzisoxa selenazoles 3 (2H) ketone) ethyl formyl ammonia) benzene selenium sulfydryl]-the 2-alanine
4. composition, described composition is made up of each described selenium thioxo cysteine benzamide compound of claim 1-3 or its pharmacy acceptable salt and halfcystine.
5. composition according to claim 4, composition formula of (I) or (II) shown in the selenium thioxo cysteine benzamide compound of structure or the mol ratio of its pharmacy acceptable salt and halfcystine be 1: 1-1: 10, be preferably 1: 2-1: 8, more preferably 1: 3～1: 6, most preferably be 1: 4-1: 5.
6. pharmaceutical composition, described composition is made up of acceptable carrier on each described selenium thioxo cysteine benzamide compound of claim 1-3 or its pharmacy acceptable salt, halfcystine and the pharmacology.
7. composition according to claim 6, selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt in the composition: the weight ratio of auxiliary material is 0.001-99: 1-99, be preferably 0.001-90: 1-95, more preferably 0.001-80: 1-90 most preferably is 0.001-70: 1-85.
8. composition according to claim 6, the weight percentage of selenium thioxo cysteine benzamide compound or its pharmacy acceptable salt is 1-99% in the composition, is preferably 5-95%, also is preferably 10-90%, more preferably 15-85% most preferably is 20-80%.
9. each described selenium thioxo cysteine benzamide compound of claim 1-3 or its pharmacy acceptable salt or each described composition of claim 4-8 have application in the anti-tumor activity medicine in preparation.
10. application according to claim 9, described tumour comprises solid tumor or leukemia, be preferably solid tumor, preferred solid tumor is selected from thyroid carcinoma, prostate cancer, colorectal carcinoma, the rectum cancer, melanoma, liver cancer, lung cancer, colorectal carcinoma, cancer of the stomach, carcinoma of submaxilary gland, nasopharyngeal carcinoma or mammary cancer, is preferably colorectal carcinoma, cancer of the stomach or carcinoma of submaxilary gland.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113527301A (en) * | 2020-04-13 | 2021-10-22 | 凯熙医药（武汉）股份有限公司 | Tetrazine substituent-containing aromatic isoselenazole compound and synthetic method and application thereof |
| WO2021223780A2 (en) | 2020-05-06 | 2021-11-11 | 上海元熙医药科技有限公司 | Use of benzisoselazole derivative for anti-coronavirus and control of interstitial lung disease (ild) related to coronavirus |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1853627A (en) * | 2005-04-25 | 2006-11-01 | 曾慧慧 | Cyclodextrin of bibenziisosehenazole ethane or cyclodextrin derivative inclusion compound, and preparation and use thereof |
| CN1990475A (en) * | 2005-12-29 | 2007-07-04 | 曾慧慧 | Substituted benzisoselenazolone compounds and use thereof |
-
2009
- 2009-01-24 CN CN200910077604A patent/CN101786976A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1853627A (en) * | 2005-04-25 | 2006-11-01 | 曾慧慧 | Cyclodextrin of bibenziisosehenazole ethane or cyclodextrin derivative inclusion compound, and preparation and use thereof |
| CN1990475A (en) * | 2005-12-29 | 2007-07-04 | 曾慧慧 | Substituted benzisoselenazolone compounds and use thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113527301A (en) * | 2020-04-13 | 2021-10-22 | 凯熙医药（武汉）股份有限公司 | Tetrazine substituent-containing aromatic isoselenazole compound and synthetic method and application thereof |
| CN113527301B (en) * | 2020-04-13 | 2024-05-17 | 凯熙医药（武汉）股份有限公司 | Tetrazine substituent-containing arylisoxazole compound and synthetic method and application thereof |
| WO2021223780A2 (en) | 2020-05-06 | 2021-11-11 | 上海元熙医药科技有限公司 | Use of benzisoselazole derivative for anti-coronavirus and control of interstitial lung disease (ild) related to coronavirus |
| WO2021223780A3 (en) * | 2020-05-06 | 2021-12-30 | 上海元熙医药科技有限公司 | Use of benzisoselazole derivative for anti-coronavirus and control of interstitial lung disease (ild) related to coronavirus |
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Application publication date: 20100728 |