The embodiments of the present invention for which an exclusive property or privilege is claimed are defined as follows: 1. A compound of the formula (l): wherein: R1 is H; R3 is hydrogen, R2 is methylene substituted by -NR7R8, or its pharmaceutically acceptable salts formed with at least one of inorganic and organic acid; wherein R7 and R8 are selected from hydrogen and alkyl having in the range of 1 up to 8 carbon atoms; wherein the inorganic and the organic acid are selected from hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, nitric acid, phosphoric acid, carbonic acid, boric acid, selenious acid, phosphomolybdic acid, phosphorous acid, sulfurous acid, citric acid, maleic acid, D-malic acid, L-malic acid, DL-malic acid, L-lactic acid, D- lactic acid, DL-Iactic acid, oxalic acid, methanesulfonic acid, valeric acid, oleic acid, lauric acid, para- toluenesulfonic acid, 1- naphthalensulfonic acid, 2-naphthaiensulfonic acid, phthalic acid, tartaric acid, malonic acid, succinic acid, fumaric acid, glycolic acid, thioglycolic acid, glycine, sarcocine, sulfonic acid, nicotinic acid, picolinic acid, isonicotinic acid, and benzoic acid; wherein X is O; Y is a single bond.

2. The compound according to claim 1, wherein, formula (I) is represented by formula (II),

3. The compound according to claim 1, wherein, formula (I) is represented by formula (V),

4. A pharmaceutical composition for cancer treatment, comprising an effective amount of the compound of any one of claims 1 to 3, in combination with a pharmaceutically acceptable carrier.

CA 02819408 2013-05-30 MICHELIOLIDE DERIVATIVES, MEDICINAL COMPOSITION, PRODUCING METHOD AND USAGE THEREOF FIELD OF THE INVENTION The present invention relates to pharmaceutical technology, and more specifically, relates to micheliolide derivatives or salt thereof, and pharmaceutical composition using which as the effective ingredient for the cancer treatment or auxiliary swelling treatment, producing methods thereof, and the usage of the compound and composition in producing anti-cancer or auxiliary anti-cancer drugs. BACKGROUND OF THE INVENTION Tumor threats the human health seriously. There are about 200 million cancer patients in China and the number is added by 1.6 million per year, which is a big group. The anti-cancer research is a challenging and significant field in life science and technology. At present, the commonly used clinical anti-cancer drugs are cytotoxic drugs. The characteristics of these drugs are poor selectivity, strong side effects, drug resistance and so on. They are a typical double-edged sword drugs, and difficult to eradicate cancer, which result in high proportion of cancer recurrence. The high rate of the recurrence of cancer has troubled the doctors, and more and more studies confirm that there are a few tumor stem cells in the tumor cell population which can amplify the cell groups. Tumor stem cells are usually in a slow cycle status and have low sensitivity to chemotherapeutic drugs. They are the source of tumor recurrence. The found of the tumor stem cell makes a new target for cancer treatment, and the drug research focused on the tumor stem cell may be able to cure cancer completely. In recent years, investigations on anti-cancer compounds from natural products have CA 02819408 2013-05-30 become the hotspot of anti-cancer drug development. For the past 20 years, 61% new small molecule entities drugs may be derived from natural products. Natural products are very common in some therapeutic areas: 78% of the antibacterial compounds and 74% of anti-tumor compounds are natural products or derived from natural products. Practice has proved that the unique role of natural products in anticancer drug discovery re-attach great attention. The traditional treatment of cancer chemotherapy drug have resistance problem, especially the low sensitivity to tumor stem cells. Traditional Chinese medicine (TCM) is profound in anti-cancer field, high efficiency and low toxicity. Accordingly, there is high chance to find drugs eradicating cancer stem cells for cure of malignant tumor from TCM. Parthenolide, a sesquiterpene lactone extracted from Tanacetum Parthenium, was originally used to treat skin infections, rheumatism, and migraine. Recent studies have shown that parthenolide can inhibit the growth of cancer cells, such as prostate cancer, breast cancer, gastric cancer, leukemia, kidney cancer, lung cancer, colon adenocarcinoma, and medulloblastoma. Furthermore, parthenolide is effective on treatment of UV- induced skin cancer in animal model. The study of its mechanism finds that parthenolide can inhibit the activation of the transcription factor NF-KB. The activity was mainly derived from the thiol on the subunit of p65/NF-KB which conducts Michael addition reaction with parthenolide. NF-KB is a key gene to regulate tumor invasion, metastasis, and drug resistance genes; therefore, inhibition of NF-KB activation may increase the sensitivity of tumor apoptosis to tumor inhibitor. Recently, Ph.D. Jordan, C. T. and his colleagues found that parthenolide can selectively eliminate cancer stem cells without damage of normal stem cells, which make it possible to suppress recurrence AML. This unique mechanism action of parthenolide has attracted

CA 02819408 2013-05-30 widespread attention. Micheliolide belongs to guaiane-type sesquiterpene lacones. It has been reported in the literature [J. Nat. Prod. 1993, 56, 90-98; Bioorg. Med. Chem. Lett. 2003, 11, 1503-1510]. On the basis of the results, the present invention reports the use of micheliolide derivatives and its salts in the cancer treatment. SUMMARY OF THE INVENTION The embodiments of present invention provides micheliolide derivative, an anti- cancer pharmaceutical composition comprising an effective amount of micheliolide derivative formula (I) or their salts, methods of preparing them, and the use of micheliolide derivative formula (I) or their salts, or their pharmaceutical composition for preparing anticancer drugs. To achieve the above-mentioned objectives, technical scheme provided includes: A compound or salt thereof of formula (I) is provided, R3 (I) E H , .K2 CiRWherein: R1 is H, -C(0)R4 or -C(0)R5R6, where R5 and R6 are the same or different, R4, R5 and R6 are hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkyaryl, arylakyl, arylalkenyl, arylalkynyl and heterocyclic; R2=R3is double bond, or

CA 02819408 2013-05-30 R3 is hydrogen, R2 is substituted alkyl having in the range of 1 up to 8 carbon atoms, where substituent is selected form cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino acid fragment, or -NR7R8, and its pharmaceutically acceptable salts formed with inorganic and/or organic acid, and including its quaternary ammonium salts formed with R9Z. Preferred substituents are amino acid fragment and methylene substituted by -NR7R8, where R7 and R8 are the same or different, they are hydrogen, alkyl, cycloalkyl, alkyl substituted by hydroxyl,alkenyl, alkynyl, aryl, alkyaryl, arylakyl, arylalkenyl, arylalkynyl, heterocyclic, trifluoromethyl, perfluoroalkyl, cyano, cyanomethyl, carboxyl, cabamate, sulfonyl, sulfonamide or aryloxyalkyl; or R7 and R8 together with N form a ring, the ring number is preferable 3-9, the ring can have one or more substituents on it, substituents are selected from hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkyaryl, arylakyl, arylalkenyl, arylalkynyl and heterocyclic, R7 and R8 are preferably selected from hydrogen, alkyl having in the range of 1 up to 8 carbon atoms, or cycloalkyl; Z is fluorine, chlorine, bromine, iodine, tosylate, methanesulfonate, benzenesulfonate, trifluoromethanesulfonate, R9 is alkyl, cycloalkyl, alkyl substituted by hydroxyl,alkenyl, alkynyl, aryl, heterocyclic, arylakyl, arylalkenyl, arylalkynyl, cyanomethyl, alkoxy or aryloxyalkyl ; inorganic or organic acid are hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, nitric acid, phosphoric acid, carbonic acid, boric acid, selenious acid, phosphonnolybdic acid, phosphorous acid, sulfurous acid, citric acid, maleic acid, D-malic acid, L-malic acid, DL-malic acid, [-lactic acid, 0-lactic acid, DL-lactic acid, oxalic acid, methanesulfonic acid, valeric acid, oleic acid, lauric acid, para- toluenesulfonic acid, 1-naphthalensulfonic acid, 2-naphthalensulfonic acid, phthalic acid, tartaric acid, malonic acid,

CA 02819408 2013-05-30 succinic acid, fumaric acid, glycolic acid, thioglycolic acid, glycine, sarcocine, sulfonic acid, nicotinic acid, picolinic acid, isonicotinic acid, benzoic acid and substituted benzoic acid; X is 0 or RioN, R1,3 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkyaryl, arylakyl, arylalkenyl, arylalkynyl or heterocyclic; Y is single bond, 0, RUN, R12R13C, R11 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkyaryl, arylakyl, arylalkenyl, arylalkynyl or heterocyclic; R12 and R13 are the same or different, they are hydrogen, fluorine, chlorine, bromine, iodine, alkyl, cycloalkyl, alkyl substituted by hydroxyl,alkenyl, alkynyl, aryl, heterocyclic, arylakyl, arylalkenyl, arylalkynyl, cyanomethyl, alkoxy or aryloxyalkyl. Herein, R1 being H, Y being single bond in not compatible with R2=R3 being double bond. Preferably, R2 is methylene substituted by -NR7R8 or amino acid fragment, where R7 and R8 are the same or different, they are hydrogen, alkyl, cycloalkyl, alkyl substituted by hydroxyl,alkenyl, alkynyl, aryl, alkyaryl, arylakyl, arylalkenyl, arylalkynyl, heterocyclic, trifluoromethyl, perfluoroalkyl, cyano, cyanomethyl, carboxyl, cabamate, sulfonyl, sulfonamide or aryloxyalkyl ;or R7 and R8 together with N form a ring, the ring number is preferable 3-9, the ring can have one or more substituents on it, substituents are selected from hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, alkyaryl, arylakyl, arylalkenyl, arylalkynyl and heterocyclic, R7 and R8 are preferably selected from hydrogen, alkyl having in the range of 1 up to 8 carbon atoms, or cycloalkyl. The invention also provide a method of producing a compound or salt thereof of formula (I), including: considering micheliolide as material, adding catalyst into organic solvent, and reacting the organic solvent with the catalyst and the material having the corresponding CA 02819408 2013-05-30 group or structure to obtain the target compound. Preferably, a compound or salt thereof of formula (I) is represented by formula (II), formula (III), formula (IV), or formula (V) ( II ) 11111111 h (T11)N - u (LO 00 (1v ) 4110 N-= HCI v). - OH H0 ...,/ OW Specifically, the invention provides a method of producing micheliolide derivative of formula (II), comprising: reacting materials to obtain the target compound of formula (II), wherein the materials are micheliolide and dimethylamine. Specifically, the invention provides a method of producing a compound of formula (IlI), comprising: reacting materials, solvent and catalyst to obtain the target compound of formula of formula (III), wherein, the materials are micheliolide and propionylchloride, the catalyst is triethylamine, and the solvent is CH2Cl2 Specifically, the invention provides a method of producing a compound of formula (IV), comprising: reacting materials and solvent to obtain the target compound of formula (IV), wherein, the materials are micheliolide and 3-chloroperbenzoic acid, the solvent is CH2Cl2. Specifically, the invention provides a method of producing a compound of formula (V), comprising: dissolving material in CH2Cl2, wherein the material is a compound of formula (II);

CA 02819408 2013-05-30 adjusting the pH to 4-5 by using of hydrochloric acid; lyophilizing the aqueous solution to obtain the compound of formula (V). The invention also provides a usage of the compound or salt thereof of formula (I) for curing a cancer, wherein, the cancer includes leukemia, breast cancer, prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer, Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giiomas, melanoma, bladder carcinoma, ovarian cancer, thyroid carcinoma, Card Posey meat cancer. The invention also provides a usage of the compound or salt thereof of formula (I) for cancer auxiliary treatment, wherein, the cancer includes leukemia, breast cancer, Prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer, Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giiomas, melanoma, bladder carcinoma, ovarian cancer, thyroid carcinoma, Card Posey meat cancer. The invention also provides a usage of the compound or salt thereof of formula (I) in a drug, wherein, the drug is used for cancer medical treatment, and the cancer includes leukemia, breast cancer, Prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer, Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giiomas, melanoma, bladder carcinoma, ovarian cancer, thyroid

CA 02819408 2013-05-30 carcinoma, Card Posey meat cancer. The invention also provides a usage of the compound or salt thereof of formula (I) in a drug, wherein, the drug is used for cancer auxiliary medical treatment, and the cancer includes leukemia, breast cancer, Prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer, Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giiomas, melanoma, bladder carcinoma, ovarian cancer, thyroid carcinoma, Card Posey meat cancer. The invention also provides a pharmaceutical composition for cancer treatment, comprising an effective amount of micheliolide derivatives or salt thereof of formula (I), in combination with a pharmaceutically acceptable carrier or other anti-cancer drug. The invention also provides usage of the compound or salt thereof of formula (II) , (Ill), (IV), (V) for curing a cancer, wherein, the cancer includes to leukemia, breast cancer, Prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer, Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giionnas, melanoma, bladder carcinoma, ovarian cancer, thyroid carcinoma, Card Posey meat cancer. The invention also provides usage of the compound or salt thereof of formula (II) , (Ill), (IV), (V) for cancer auxiliary treatment, wherein, the cancer includes leukemia, breast cancer, Prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer,

CA 02819408 2013-05-30 Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giiomas, melanoma, bladder carcinoma, ovarian cancer, thyroid carcinoma, Card Posey meat cancer. The invention also provides usage of the compound or salt thereof of formula (II) , (Ill), (IV), (V) in a drug, wherein, the drug is used for cancer medical treatment, and the cancer includes leukemia, breast cancer, Prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer, Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giiomas, melanoma, bladder carcinoma, ovarian cancer, thyroid carcinoma, Card Posey meat cancer. The invention also provides usage of the compound or salt thereof of formula (II) , (Ill), (IV), (V) in a drug, wherein, the drug is used for cancer auxiliary medical treatment, and the cancer includes leukemia, breast cancer, Prostate cancer, nasopharyngeal carcinoma, colorectal cancer, lung cancer, liver cancer, esophageal carcinoma, gastric cancer, intestinal cancer, renal carcinoma, oral cavity cancer, Hochkin lymphoma, pancreas cancer, colorectal cancer, cervical cancer, Non Hochkin lymphoma, giiomas, melanoma, bladder carcinoma, ovarian cancer, thyroid carcinoma, Card Posey meat cancer. The invention also provides a pharmaceutical composition for cancer treatment, comprising an effective amount of micheliolide derivatives or salt thereof of formula (II), (Ill), (IV), (V), in combination with a pharmaceutically acceptable carrier or other anti-cancer drug. The compounds in the embodiments of the present invention can be used directly or in the form of pharmaceutical composition as drug. The pharmaceutical compositions contain

CA 02819408 2013-05-30 0.1-99%, preferred 0.5-90% compounds of the present invention, and others are pharmaceutically acceptable pharmaceutical carrier and/or excipient which are harmless to animal and human or composition with other anti-cancer drug. Compositions in the embodiments of the present invention may be formulated as injection, tablet, and capsule. The pharmaceutical carrier and excipient are a kind or many kinds of solid, semi-solid or liquid thinner and adjuvant drug. The dosage of pharmaceutical composition of the present invention may be based on unit weight. The compounds of the invention can be administrated by injection and oral form. The injection includes intravenous injection and intramuscular injection, and the oral form may be tablets and capsules. Micheliolide derivatives or salt thereof in the embodiments of the present invention show good effect on cancer treatment, and no obvious inhibition to normal cells. DETAILED DESCRIPTION OF THE INVENTION The present invention is further described in detail hereinafter with reference to the accompanying drawings as well as embodiments so as to make the objective, technical scheme and merits thereof more apparent. Embodiment 1 The producing of 113H,13-Dihydro, 13-dinnethylaminomicheliolide (compound II, which is represented by formula (II)) ( ) CA 02819408 2013-05-30 Micheliolide (106 mg, 0.40 mmol), triethylamine (2.0 mL), Me2NH HCI (41 mg, 0.5 mmol), and methanol (30 mL) are added to a 100-mL round flask. The resulting mixture is heated and refluxed for 3 hours, and then concentrated under reduced pressure to obtain crude residue which is purified by silica gel column chromatography (petroleum ether: ethyl acetate: triethylamine = 50:50:0.5) to obtain 107.4 mg white solid, wherein, the yield is 86%. Formula: C17H27NO3 Molecular weight: 293 Properties: white amorphous powder Spectra data: 1H NMR (CDCI3, 400 MHz) 6 3.76 (t, J = 10.0 Hz, 1H), 2.96 (s, 1H), 2.49-2.67 (m, 3H), 2.28-2.34 (m, 1H), 2.30-2.34 (m, 2H), 2.18 (s, 6H), 2.09 (br s, 2H), 1.96 (d, J = 11.2 Hz, 1H) 1.67-1.73 (m, 2H), 1.60(s, 3H), 1.22 (br s, 3H),1.18 (br s, 2H); 13C NMR (CDCI3, 300 MHz) 6 177.0, 131.8, 131.3, 84.0, 80.2, 58.3, 58.1, 50.9, 46.0, 44.6, 38.4, 35.3, 30.0, 27.2, 23.7, 22.8. Embodiment 2 The producing of 4¨propionylmicheliolide (Compound III, which is represented by formula (III)) (III) (3 0 (LO 0 Micheliolide (106 mg, 0.40 mmol), triethylamine (2.0 mL), propionylchloride (0.2 mL) and CH2Cl2 (5 mL) are added to a 20-mL round flask. The resulting mixture is stirred for 3 hour at

CA 02819408 2013-05-30 room temperature, and then concentrated under reduced pressure, and purified by using silica gel column chromatography (petroleum ether: ethyl acetate = 90:10) , and finally 84 mg white solid are obtained. Wherein, the yield is 72%. Formula: C18H24N04 Molecular weight: 304 Properties: white amorphous powder Spectra data: 1H NMR (CDCI3, 400 MHz) 6 6.14 (s, 1H), 5.42 (s, 1H), 3.74 (t, J = 10.0 Hz, 1H), 1.80-2.74 (m, 12H), 1.67 (s, 3H), 1.50 (s, 3H), 1.07 (t, J = 4.0 Hz, 3H); 13C NMR (CDCI3, 300 MHz) 6173.8, 170.1, 139.5, 131.5, 130.4, 118.6, 88.4, 83.0, 56.6, 50.1, 36.5, 34.9, 30.4, 28.7, 25.9, 24.1, 18.8, 9.1. Embodiment 3 The producing of 1,10-Epoxymicheliolide (Compound IV, its structure was represented by formula (IV))111141110 (IV) OF 6- Micheliolide (106 mg, 0.40 mmol), m-CPBA (2.0 mL), and CH2Cl2 (5 mL) are added to a 20-mL round flask. The resulting mixture is stirred for 6 hours at the room temperature, and then concentrated under reduced pressure, purified by using silica gel column chromatography (petroleum ether: ethyl acetate = 80:20) ,and finally 96 mg white solid are

CA 02819408 2013-05-30 obtained. Wherein, the yield is 91%. Formula: C15H20N04 Molecular weight: 264 Properties: white amorphous powder Spectra data: 1H NMR (CDCI3, 400 MHz) 8 6.13(t, J = 3.2 Hz, 1H), 5.44 (d, J = 2.8 Hz, 1H), 3.73(t, J = 10.4 Hz, 1H), 1.30-2.46 (m, 11H), 1.29 (s, 3H), 1.28 (s, 3H); 130 NMR (CDCI3, 300 MHz) 6 168.7, 137.8, 118.6, 79.2, 77.3, 74.2, 66.7, 52.6, 48.4, 37.1, 33.8, 29.0, 24.6, 22.5, 21.3. Embodiment 4 The producing of 11131-1,13-Dihydro, 13-dimethylaminomicheliolide hydrochloride (Compound V, its structure was represented by formula (V)) N¨ = NCI 6H H8 ...,1 0 (v) compound 11 (293 mg, 1 mmoI) is dissolved in CH2Cl2 (2 mL) and was Stirred at room temperature, hydrochloric acid is added until pH = 4-5. The mixture was extracted with CH2Cl2 (2x10 mL). The aqueous layer is lyophilized to obtain white solid, wherein, the yield is 82%. The structure data of the produced 11S, 11, 13-Dihydro, 13- dimethylaminomicheliolide hydrochloride are as follows:

CA 02819408 2013-05-30 Formula: C17H28C1NO3 Molecular weight: 328.5 Properties: White amorphous powder Spectra data: [a]D20= ¨42.0 (c= 10, H20); IR (KBr): 3334, 2927, 2856, 1767, 1467, 992, 967, 719, 669, 626, 504 cm-1; 1H NMR (D20, 400 MHz) 5 4.14 (t, J = 10.3 Hz, 1H), 3.51 (q , J = 12.6 Hz, 1H), 3.40 (dd , J = 13.3, 2.9 Hz, 1H), 3.18-3.04 (m, 1H), 2.96 (d , J = 10.6 Hz, 6H), 2.67 (d , J = 10.2 Hz, 1H), 2.37 (dd , J = 16.2, 8.1 Hz, 1H), 2.27-2.05 (m, 4H), 1.87 (d , J = 12.9 Hz, 1H), 1.73 (dd , J= 19.5, 11.7 Hz, 2H), 1.66(s, 3H), 1.46-1.31 (m, 2H), 1.26 (s, 3H); 13C NMR (CDCI3, 100 MHz) 5 178.4, 132.6, 131.4, 85.1, 80.7, 56.9, 55.6, 49.9, 45.1, 42.3, 41.5, 39.2, 34.4, 29.5, 25.9, 23.2, 21.4. Embodiment 5: The pharmacological of micheliolide derivatives. A variety of cancer cells are suspended to 2x105/mL, and then added into 24- hole Round-bottomed tissue culture plate. After that micheliolide and its derivatives are added, herein a test with one density occupies 5 holes. The resulting suspension are incubated (under 37 C, 5% CO2) for 18 hours to allow the compounds to take effect. A absorbance (A) value is measured by using the method of MTT assay and an enzyme-linked detector under 570 nm wavelength, and then the inhibitory activity of the compounds is concluded. The result of the inhibitory activity is shown in Table 1. Tablel. The inhibitory activity of micheliolide and its derivatives against different cancer cells (IC50, PM)

CA 02819408 2013-05-30 Cell lines Compound II Compound III Compound IV Compound V HL-60 2.4 4.5 5.8 11.5 K562 4.2 6.7 9.7 21.4 MCF-7 4.6 3.4 8.9 26.8 CNE-1 11.2 5.9 6.7 22.5 CNE-2 16.5 12.4 5.6 16.9 SW620 5.8 5.6 3.8 13.5 A549 7.2 7.7 5.7 18.1 HepG-2 4.5 15.4 7.4 27.9 Ec9706 9.2 7.6 6.6 15.7 SGC7901 14.6 14.7 13.4 24.9 SW1116 11.5 21.5 11.7 31.2 A498 12.4 5.3 4.3 16.3 ASPC-1 3.9 15.1 26.4 33.6 HT-29 4.8 9.8 9.8 19.2 HeLa 9.4 17.3 9.7 33.4 GL15 12.6 14.3 21.5 25.8 B16F1 3.4 13.2 5.2 18.6 T24 14.2 13.6 7.9 22.5 SKOV3 5.9 9.4 10.4 15.4 SW579 17.3 22.5 12.4 32.6 PC-3 8.7 11.4 17.2 23.5 CA 02819408 2013-05-30 In Table 1, HL-60, K562, MCF-7, CNE-1, CNE-2, SW620, A549, HepG2, Ec9706, SGC7901, SW1116, A498, ASPC-1, HT-29, HeLa, GL15, B16F1, T24, SKOV3, SW579, P0-represents acute leukemia cell lines, Chronic leukemia cell lines, Breast cancer cell lines, High differentiation nasopharyngeal carcinoma cell line, Poorly differentiated nasopharyngeal carcinoma cell lines, Colorectal cancer cell line, Lung cancer cell lines, Hepatocellular carcinoma cell lines, Esophageal cancer cell line, Gastric cancer cell line, Colon cancer cell line, Renal cell carcinoma cell line, Pancreatic cancer cell line, Colon cancer cell lines, uterine cervical cancer cell lines, Horny man neuroblastoma cell lines, Melanoma cell line, human bladder cancer cell line, ovarian cancer cell lines, thyroid cancer cells, prostate cancer cell lines, respectively. The tested result shows the compounds show strong inhibitory activity against the tested cells, however, have no obvious inhibition against normal cells at 50 pM. Embodiment 6 Injection Compounds II, Ill, IV, V produced in the embodiments 1 to 4, is respectively dissolved in a small amount of DMSO. Injective water is then added into the mixed solvent and filtered finely, after potting and sterilization, Finally the injection is obtained. Embodiment 7 Tablet The compounds II, Ill, IV, V produced in the embodiments 1 to 4, is mixed respectively with excipients according to weight ratio of 5:1, and then tableted to obtain tablets. Embodiment 8 Capsule The compounds II, III, IV, V prepared in the Examples 1-4, is mixed respectively with excipients according to weight ratio of 5:1 to obtain capsules.

CA 02819408 2016-03-04 PPH The compounds, usage and producing methods of the present invention have been described with specific embodiments. It is obviously for those skilled in the art to appropriately change raw materials, process conditions et al, to achieve corresponding purposes. The scope of the claims should not be limited by the preferred embodiments set forth herein, but should be given the broadest interpretation consistent with the description as a whole.