CN1603307A

CN1603307A - Cyanoacrylate derivatives and their preparation method and biological activity

Info

Publication number: CN1603307A
Application number: CN 200410040350
Authority: CN
Inventors: 杨松; 金林红; 宋宝安; 钟惠民; 刘刚
Original assignee: Guizhou University
Current assignee: Guizhou University
Priority date: 2004-07-30
Filing date: 2004-07-30
Publication date: 2005-04-06
Anticipated expiration: 2024-07-30
Also published as: CN1317265C

Abstract

This invention discloses a medicine of anti-tumor and anti-plant virus effect---- cyanoacrylate category derivative and its preparing method and biological activity. The following general formula denotes the compound and its preparing method. The definition of R1, R2, R3 in the formula is in instruction book. Materials are carbon bisulfide, cyan acetic ester, dimethyl sulfate, aromatic amine, and sodium cyanide is catalyst, cyanoacrylate category derivative is synthesized by three steps. There is proliferation inhibitory effect of compound b, k to PC3 prostate cancer cell gene stock, and proliferation inhibitory effect of compound i, j to NIN3T3 cell ERK albumen phosphorylation, and good anti-cancer activity is revealed. There is inhibitory activity of compound b, n to tobacco mosaic, and certain anti-plant virus activity is revealed.

Description

Cyanacrylate derivant and preparation method and biological activity

Technical field

The present invention has antitumor and the medicine Antiphytoviral effect is cyanacrylate derivant and preparation method thereof.

The action target that the selective light cooperation is used as weedicide is the needs of world today's initiative environment friendly agricultural, Deisenhofer (Deisenkorfer.J in 1985, Epp.O.Miki.K.et al, Nature, 1985,318 (12): 618) adopt the X-diffraction approach successfully to solve the three-dimensional arrangement of electron transfer system protein involved in the Chromobacterium violaceum photosynthesis, this achievement in research makes the novel inhibitor of photosynthesis that designs based on receptor model become world today's research focus, studies show that the 2-cyanoacrylate is that a class suppresses the important weedicide of photosynthesis of plant, it acts on same target---plastoquinone QB combining site among the photosynthesis PSII, the plastoquinone QB of competitive replacement and D1 protein bound, cause the electron transport (Tietjen.K.G that is obstructed, Kluth.J.F, Andree.R.et al, Pesticide Science, 1991,31:65-71; Fuerst.E.P, Norman.M.A, WeedScience, 1991,39:458).Because acrylic ester compound has the mechanism of action novelty, nontoxic to beneficial organism, environmental friendliness has become domestic and international pesticide research important directions.

Background technology

Cyanoacrylate compound is because of its novel mechanism of action, and characteristics such as environmentally friendly became the focus of domestic and international medical research in recent years.

Aspect insecticidal activity: people (Yu Shenyi such as surplus Shen Yi in 2002, Li Zhengming .2-cyano group-3-[(6-chlorine)-and the 3-picolyl] synthetic [J] of amino-3-fat amido ethyl propenoate. the Pesticide Science journal, 2002,4 (3): 79-82) report from ethyl cyanoacetate through 3, the reaction of 3-diformazan sulfenyl-2-cyanacrylate and 3-amino methyl or 5-chloro-3-aminomethyl-pyridine obtains intermediate, obtains target compound 3-aromatic amino-3-alkylamine-2-cyanoacrylate without separating directly to react with aliphatic amide.

Aspect weeding activity: (Liu H Y such as Liu Hua silver in 1999, Dai G X, Tan H F, etal.Synthesis of Novel Derivatives of2-Cyano-3-Methylthio-3 '-Benzylamino-acrylates (Acryl amides) andTheir Biological Activity[J] .Phosphorus, Sulfur and Silicon 1999,148,235-241.) report, adopt cyan-acetic ester or malonamide nitrile in the presence of the highly basic sodium hydride, with the dithiocarbonic anhydride effect, use the methyl-sulfate alkylation, obtain 2-cyano group-3-methylthio group-3 '-amino acrylates (or acrylamide) with the benzylamine effect again.In the greenhouse, cultivate pea (Pisumsatinon), at seedling age in the time of 20 days, chloroplast(id) is suspended in the extracting solution, make Chloroplast Suspension, measure the inhibition activity of compound to Hill, concentration of treatment by compound and put relation curve between oxygen activity, the volumetric molar concentration when the computerized compound suppresses the 50%Hill reaction is (with PI ₅₀Expression), after tested, the PI of a certain compound ₅₀Reach 8.30.Zhao Yi had just waited people (Zhao Yigang in 1999, Liu Xin, Huang Runqiu, synthetic and biological activity [J] Deng .2-cyano group-3-substituted amido (or methylthio group)-3-(2-chloro-5-pyridyl-methanamine base)-acrylic ester compound. the Pesticide Science journal, 1999,1 (1): 93-95.) the synthetic and biological activity of report 2-cyano group-3-substituted amido (or methylthio group)-3-(2-chloro-5-pyridyl)-acrylic ester compound, through preliminary biological activity test, cauline leaf is handled, formulation rate 1500g/ha, target compound is 96.6% to the rape inhibiting rate.People (Liu Huayin such as Liu Hua silver in 2000; Tan Huifen; Yang Huazheng. the synthetic and Hill reaction of biological appropriate design photosystem II inhibitor research (VI)-2-cyano group-3-methylthio group-basic ethyl propenoate of 3-alkane ammonia (benzyl ammonia) suppresses active [J]. SCI; 2000; 21 (12): 1855-1857.) on the basis of comparing the homologous protein structure; set up the 3 d structure model of pea (pisum satirum) photosynthetic reaction center 32kD albumen (D1) with homology mould construction method; and carried out novel inhibitor of photosynthesis molecular designing based on acceptor D1 protein structure, synthesized 2-cyano group-3-methylthio group-3-alkane ammonia (benzyl amino) ethyl propenoate.Biological activity determination is the result show, overwhelming majority compound shows Hill reaction preferably and suppresses active, and there are certain rule in this compounds structure and activity, for the alkylamino compound, along with the increase of alkyl carbon atoms number, the Hill of compound reaction suppresses active to be increased (from PI ₅₀Be 4.88 to 6.17), after chiral radicals was introduced in benzyl α position, the three-dimensional arrangement of molecule had considerable influence to activity, and from the test activity data as seen, its raceme exceeds tens of times than R body activity.Grandson understood triumphant (Sun Huikai such as grade in 2002, the people of Wangqing County, Li Ya, Deng. contain the synthetic and weeding activity research [C] of cyanoacrylate compound of ferrocenyl. the 11 nd Annual Meeting collection of agricultural chemicals Professional Committee of Chemical Industry and Engineering Society of China, Chengdu 2002,222-223.) report is for the characteristic of acceptor pocket and very few with benzylamine group research in the compound of its effect, consider ferrocene be one than the bigger and better group of hydrophobicity of benzene volume, study the characteristic of such weedicide acceptor pocket with the phenyl ring in its alternative cyanoacrylate, with the ferrocene benzylamine is raw material, has synthesized the cyanoacrylate compound that contains ferrocene of seven novelties with cyanoacrylate.Adopt pot-culture method that institute's synthetic compound has been carried out weeding activity mensuration, 1-1.5 phase cauline leaf processing behind preceding soil treatment of seedling and the seedling was handled 10 days after broadcasting, and calculated inhibiting rate.By test result as can be known, part of compounds shows better weeding activity to cruciferous weeds such as rapes.Wang Feng cloud (Wang Fengyun in 2003, Guo Liqin, horse naval, synthetic and weeding activity research [C] Deng .2-cyano group-3-substituted-phenyl-3-substituted-amino acrylamide compound. the 5th novel pesticide initiative exchanging meeting collection of thesis, Shenyang, 2003, agricultural chemicals Professional Committee of Chemical Industry and Engineering Society of China) two class acrylamide compounds with Stauffer company report are lead compound, with 2-cyano group-3-methoxyl group-3-substituted-phenyl vinyl cyanide is initiator, synthetic a series of 3-substituted-phenyls-2-cyano group acrylamides.Through preliminary active testing, under 500g/ha dosage, potted plant bud pre-treatment has good preventive effect to Tong fiber crops, dog tail, lady's-grass, Herba Eleusines Indicae, chickweed, Persian veronica, shepherd's purse.The people of Wangqing County (Wang Q M in 2004, San HK, Huang R Q.Synthesis and Herbicidal Activity of (Z)-Ethoxyethyl2-cyano-3-(2-methylthio-5-pyridylmethglamino) acrylates[J] .Heteroatom Chemistry, 2004,15 (1): 67-70.) wait the people to report the synthetic and biological activity of 2-ethoxyethyl-2-cyano group-3-(2-methyl sulfenyl)-5-pyridyl-methanamine base acrylate.Show that through biological activity test target compound is under the 1.5kg/ha at drug concentration, rape flower section weeds inhibiting rate is reached 98.4%.

Aspect new synthetic method: (Chen Kai such as calendar year 2001 Chen Kai; Yang Huazheng; Liu Zhun; Deng. phosphono under the microwave irradiation/thiomethyl ketenes sulfo-acetal and N-replace synthetic [J] of phosphono/thiomethyl thiocarbonic ester. organic chemistry; 2001; 21 (9): 690-692.) adopt microwave irradiation; make solvent with anhydrous tetrahydro furan; ketenes dithioacetals and N-replace dithiocarbonates and with the phosphonous acid alkyl ester conjugate addition reaction takes place apace in the presence of excessive N aH, synthesize corresponding alpha-cyano-phosphono/thiomethyl ketenes sulfo-acetal compound and N-and replace phosphono/thiomethyl thiocarbonic acid SOH ester compound.More as can be seen, microwave irradiation has been accelerated speed of reaction greatly, has improved reaction yield from corresponding data.At room temperature, although prolong the reaction times, conjugate addition does not take place in some reactions substantially yet, yet under microwave irradiation, reaction can more easily take place, and productive rate can reach 80%.Grandson understood triumphant (Sun Huikai such as grade in 2002, Cao Huanyan, the people of Wangqing County, Deng. contain the synthetic and weeding activity research [C] of the cyanoacrylate compound of heterocyclic methyl amine. the 11 nd Annual Meeting collection of agricultural chemicals Professional Committee of Chemical Industry and Engineering Society of China, Chengdu, agricultural chemicals Professional Committee of Chemical Industry and Engineering Society of China, 2002,218-221.) row's principle such as applying biological and activity methods be to containing the S of pyridine methylene, N-ketene acetal structure is optimized and modifies, with the hydrogen atom on the pyridine ring with replacements such as alkoxyl groups, or pyridine and other heterocyclic substituted, or change alkylthio into alkyl etc., a series of cyanoacrylate compound that contain heterocyclic methyl amine have been synthesized in design, and the synthetic route of intermediate is improved, and find that the ortho acid triester method has the route weak point, simple to operate, the advantage that raw materials cost is low, in intermediate synthetic, use direct heating instead, do not use catalyzer KI, change the outward appearance of product, shortened the reaction times, yield also increases.Adopt pot-culture method that institute's synthetic compound has been carried out weeding activity mensuration, bioassay results shows with the alpha-cyanoacrylate ester cpds behind the pyridine replacement benzene to have better weeding activity, 2 chlorine atom in the picolyl amine is replaced its high herbicidal activity of back with alkoxyl group still keep, but along with the slightly downtrending of its activity of increase of alkoxyl group.

Cyanoacrylate compound has particular structure and novel mechanism of action, uses extensively day by day in agricultural herbicide, is worth further further investigation.And investigator seminar finds that at work the part cyanoacrylate compound has resisting tobacco mosaic disease (TMV) and antitumour activity recently, the objective of the invention is to be according to this basis, to suppress the photosynthesis of plant cyanoacrylate is lead compound, introduce fluorine atom or heterocyclic group, design novel cyanoacrylate compound, carry out cancer therapy drug and novel pesticide initiative research.

Summary of the invention

To suppress the photosynthesis of plant cyanoacrylate is lead compound, introduces fluorine atom or heterocyclic group, and design synthesizing new structure cyanoacrylate compound is carried out novel pesticide and cancer therapy drug initiative research.Its general structure is as follows:

In the formula

R ₁Be the C1-6 alkyl.

Work as R ₂When being respectively hydrogen, C1-10 alkyl, C3-8 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl group, C1-10 alkyl sulphonyl, C2-10 alkenyl alkylsulfonyl, C2-10 alkynyl group alkylsulfonyl, C1-10 alkyl-carbonyl, C2-10 alkenyl carbonyl, C2-10 alkynyl group carbonyl, R ₃Be respectively the fluoro aromatic group of C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) hydroxyl, (2) halogen atom, (3) itrile group, (4) nitro, (5) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (7) C1-6 alkylthio, C2-6 alkenyl thio or C2-6 alkynes sulfenyl, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (8) substituted carbonyl, described substituting group is selected from (i) C1-6 alkyl, (ii) amino, (iii) C1-6 alkylamino, (iv) C1-6 alkyl oxy, (v) C1-6 alkyl sulfenyl, (vi) C3-8 cycloalkyl, (9) can be by the amino of 1 or 2 each substituting groups replacement, described substituting group is selected from (i) C1-6 alkyl, (ii) C2-6 alkenyl, (iii) C2-6 alkynyl group, (iv) C1-6 alkyl sulphonyl, (v) C2-6 alkenyl alkylsulfonyl, (vi) C2-6 alkynyl group alkylsulfonyl, (vii) C1-6 alkyl-carbonyl, (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl, (10) C1-6 alkyl sulphonyl, (11) C2-6 alkenyl alkylsulfonyl, (12) C2-6 alkynyl group alkylsulfonyl, (13) C1-6 alkyl sulphinyl, (14) C2-6 alkenyl sulfinyl, (15) C2-6 alkynyl group sulfinyl, (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group;

Work as R ₃When being respectively hydrogen, C1-10 alkyl, C3-8 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl group, C1-10 alkyl sulphonyl, C2-10 alkenyl alkylsulfonyl, C2-10 alkynyl group alkylsulfonyl, C1-10 alkyl-carbonyl, C2-10 alkenyl carbonyl, C2-10 alkynyl group carbonyl, R ₂Be respectively the fluoro aromatic group of C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) hydroxyl, (2) halogen atom, (3) itrile group, (4) nitro, (5) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (7) C1-6 alkylthio, C2-6 alkenyl thio or C2-6 alkynes sulfenyl, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (8) substituted carbonyl, described substituting group is selected from (i) C1-6 alkyl, (ii) amino, (iii) C1-6 alkylamino, (iv) C1-6 alkyl oxy, (v) C1-6 alkyl sulfenyl, (vi) C3-8 cycloalkyl, (9) can be by the amino of 1 or 2 each substituting groups replacement, described substituting group is selected from (i) C1-6 alkyl, (ii) C2-6 alkenyl, (iii) C2-6 alkynyl group, (iv) C1-6 alkyl sulphonyl, (v) C2-6 alkenyl alkylsulfonyl, (vi) C2-6 alkynyl group alkylsulfonyl, (vii) C1-6 alkyl-carbonyl, (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl, (10) C1-6 alkyl sulphonyl, (11) C2-6 alkenyl alkylsulfonyl, (12) C2-6 alkynyl group alkylsulfonyl, (13) C1-6 alkyl sulphinyl, (14) C2-6 alkenyl sulfinyl, (15) C2-6 alkynyl group sulfinyl, (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group;

R ₂, R ₃Can be respectively the fluoro aromatic group of C5-14 simultaneously, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) hydroxyl, (2) halogen atom, (3) itrile group, (4) nitro, (5) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (7) C1-6 alkylthio, C2-6 alkenyl thio or C2-6 alkynes sulfenyl, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (8) substituted carbonyl, described substituting group is selected from (i) C1-6 alkyl, (ii) amino, (iii) C1-6 alkylamino, (iv) C1-6 alkyl oxy, (v) C1-6 alkyl sulfenyl, (vi) C3-8 cycloalkyl, (9) can be by the amino of 1 or 2 each substituting groups replacement, described substituting group is selected from (i) C1-6 alkyl, (ii) C2-6 alkenyl, (iii) C2-6 alkynyl group, (iv) C1-6 alkyl sulphonyl, (v) C2-6 alkenyl alkylsulfonyl, (vi) C2-6 alkynyl group alkylsulfonyl, (vii) C1-6 alkyl-carbonyl, (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl, (10) C1-6 alkyl sulphonyl, (11) C2-6 alkenyl alkylsulfonyl, (12) C2-6 alkynyl group alkylsulfonyl, (13) C1-6 alkyl sulphinyl, (14) C2-6 alkenyl sulfinyl, (15) C2-6 alkynyl group sulfinyl, (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group;

X is NH, S, O, SO or SO2.

Above-described a kind of antitumor and medicine Antiphytoviral of being used for, R in its compound general formula ₃Fluoro aromatic group for C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected white following substituent group to replace by one or more on the above-mentioned cyclic group: (1) halogen atom, (2) itrile group, (3) nitro, (4) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group.

Above-described a kind of antitumor and medicine Antiphytoviral of being used for, R in its compound general formula ₂Be hydrogen; the C1-10 alkyl; the C3-8 cycloalkyl; the C2-10 alkenyl; the C2-10 alkynyl group; the C1-10 alkyl sulphonyl; C2-10 alkenyl alkylsulfonyl; C2-10 alkynyl group alkylsulfonyl; the C1-10 alkyl-carbonyl; the C2-10 alkenyl carbonyl; C2-10 alkynyl group carbonyl; the fluoro aromatic group of C5-14; contain 1 or a plurality of N of being selected from; O; S; the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2; and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom; (2) itrile group; (3) nitro; (4) C1-6 alkyl; C2-6 alkenyl or C2-6 alkynyl group; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (6) C1-6 alkoxyl group; C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group.

Above-described a kind of antitumor and medicine Antiphytoviral of being used for, R in its compound general formula ₁Be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl, tert-pentyl, neo-pentyl.

Above-described a kind of antitumor and medicine Antiphytoviral of being used for, X is NH, S, O in its compound general formula.

Above-described a kind of antitumor and medicine Antiphytoviral of being used for, R in its compound general formula ₂Or R ₃For containing fluorophenyl; pyrryl; furyl; tetrahydrofuran base; thienyl; thiazolyl; isothiazolyl; imidazolyl; pyrazolyl oxazolyl isoxazolyl; triazolyl; tetrazyl; thiadiazolyl group; pyridyl; morpholinyl; piperazinyl; triazinyl; piperidyl; pyridazinyl; pyrimidyl; purine radicals; pyrazinyl; naphthyl; quinolyl; isoquinolyl; phthalazinyl; naphthyridinyl; indyl; draw the azoles base; benzofuryl; benzimidazolyl-; benzothiazolyl; benzisothiazole base benzoxazolyl; the benzoisoxazole base; the benzopyrazoles base; quinazolyl; different quinazolyl; dibenzofuran group; the dibenzothiophene base; the bisbenzimidazole base; the dibenzo pyrimidyl; the dibenzopyridine base; carbazyl; and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom; (2) itrile group; (3) nitro; (4) C1-6 alkyl; C2-6 alkenyl or C2-6 alkynyl group; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (6) C1-6 alkoxyl group; C2-6 alkenyloxy or C2-6 chain oxy-acetylene; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (7) C1-6 alkylthio; C2-6 alkenyl thio or C2-6 alkynes sulfenyl; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (8) substituted carbonyl; described substituting group is selected from (i) C1-6 alkyl; (ii) amino; (iii) C1-6 alkylamino; (iv) C1-6 alkyl oxy; (v) C1-6 alkyl sulfenyl; (vi) C3-8 cycloalkyl; (9) can be by the amino of 1 or 2 each substituting groups replacement; described substituting group is selected from (i) C1-6 alkyl; (ii) C2-6 alkenyl; (iii) C2-6 alkynyl group; (iv) C1-6 alkyl sulphonyl; (v) C2-6 alkenyl alkylsulfonyl; (vi) C2-6 alkynyl group alkylsulfonyl; (vii) C1-6 alkyl-carbonyl; (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl; (10) C1-6 alkyl sulphonyl; (11) C2-6 alkenyl alkylsulfonyl; (12) C2-6 alkynyl group alkylsulfonyl; (13) C1-6 alkyl sulphinyl; (14) C2-6 alkenyl sulfinyl; (15) C2-6 alkynyl group sulfinyl; (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group.

Above-described a kind of antitumor and medicine Antiphytoviral of being used for, R in its compound general formula ₂Or R ₃Be the 4-trifluoromethyl, 2-chloro-4-picoline-3-base, 2,6-dichlor-4-trifluoromethyl phenyl, 2-fluoro-5-trifluoromethyl, 2-fluoro-3-trifluoromethyl, 2-bromo-5-fluorophenyl, 2-bromo-4, the 6-difluorophenyl, 5-methyl isoxzzole-3-base, 2-methoxyl group diphenylene-oxide-3-base, 1-tolimidazole-2-base, the 4-bromophenyl, 6-fluoro benzothiazole-2-base, 4-methylbenzothiazole-2-base, 6-methylbenzothiazole-2-base, 6-methoxyl group benzo thiazol-2-yl, 6-ethoxyl benzo thiazole-2-base, 2-bromo-4, the 6-3,5-dimethylphenyl, 4-bromo-2, the 6-dichlorophenyl, 4-bromo-2-chloro-phenyl-, 6-nitrobenzene thiazole-2-base, nicotinic acid-2-base, pyrazine-2-formic acid-3-base, 4-fluorobenzoic acid-2-base, 5-fluorobenzoic acid-2-base, 6-fluorobenzoic acid-2-base, 4,5-dimethoxybenzoic acid-2-base, 5-iodo-benzoic acid-2-base, 1-trifluoromethyl-2-fluorobenzene-5-base, 1-trifluoromethyl-5-bromobenzene-2-base, 1-trifluoromethyl-5-fluorobenzene-2-base, 1-trifluoromethyl-4-bromobenzene-3-base, 1-trifluoromethyl-3-bromobenzene-4-base, 5-bromopyridine-2-base, pyridine-2-formic acid-3-base, (S)-the Alpha-Methyl benzylamine, (R)-the Alpha-Methyl benzylamine.

In the content of the present invention, the C1-6 alkyl can be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl, tert-pentyl, neo-pentyl, n-hexyl, isohexyl, uncle's hexyl, new hexyl.

In the content of the present invention, the C2-6 alkenyl can be vinyl, propenyl, allyl group, (two keys are at 1 for butenyl, two or three-digit), isobutenyl (two keys are at 1 or 2), (two keys are at 1 for pentenyl, 2,3 or 4), (two keys are at 1 for isopentene group, two or three-digit), new pentenyl (two keys are at 1 or 2), (two keys are at 1 for hexenyl, 2,3,4 or 5), (two keys are at 1 for dissident's thiazolinyl, 2, in the content of the present invention, the C2-6 alkynyl group can be ethynyl, proyl, propargyl, (three key is at 1 for butynyl, two or three-digit), isobutyl alkynyl (three key is at 1 or 2), (three key is at 1 for pentynyl, 2,3 or 4), (three key is at 1 for the isoamyl alkynyl, two or three-digit), new pentynyl (three key is at 1 or 2), (three key is at 1 for the hexin base, 2,3,4 or 5), (three key is at 1 for dissident's alkynyl, 2,3 or 4), (three key is at 1 for new hexin base, two or three-digit).

In the content of the present invention, halogen atom can be fluorine, chlorine, bromine, iodine.

In the content of the present invention, the fluoro aromatic group is meant replacement on replacement, the fluorine-containing aromatic ring of F1-12, fluoro-alkyl substituted aroma ring, fluoroalkane alkenylsubstituted aromatic ring, fluoroalkane alkynyl substituted aromatic nucleus and above-mentioned fluorine-containing combination on different positions thereof on the fluorine-containing phenyl ring of F1-5.As: 2-fluoro-3-trifluoromethyl, 2-fluoro-5-trifluoromethyl, 2,6-dichlor-4-trifluoromethyl phenyl, 4-trifluoromethyl, 6-fluoro benzothiazole-2-base, 2-bromo-5-fluorophenyl, 2-bromo-4,6-difluorophenyl etc.

In the content of the present invention, can be a kind of pharmaceutical composition, it is characterized in that comprising formula (I) compound or its pharmacy acceptable salt of significant quantity, its purposes is as treatment and prevents various optimum or malignant tumours.Wherein said tumour comprises prostate cancer, leukemia, skin carcinoma, cancer of the stomach, mammary cancer, liver cancer, lung cancer, ovarian cancer, cervical cancer, lymphatic cancer, large bowel cancer, nasopharyngeal carcinoma, oral carcinoma, wherein is meant prostate cancer especially.

Described pharmaceutical composition contains the mixture as formula at least (I) compound of activeconstituents itself or itself and one or more pharmaceutically useful inert non-toxic vehicle or carrier.

Acceptable salt also can be used for preventing and treating plant virus, weeds, the animal pest that appears on husbandry, the forest aspect as activeconstituents in The compounds of this invention or its plant protection, and stores the animal pest on product, material protection, the health aspect.The compounds of this invention also can be used as defoliating agent, weedicide, anti-plant virus agent as activeconstituents.Particularly The compounds of this invention has good active to tobacco mosaic disease (TMV) as anti-plant virus agent the time.

The present invention is to be raw material with dithiocarbonic anhydride, cyan-acetic ester, methyl-sulfate, aromatic amine, with ethanol, Virahol, dehydrated alcohol, N, dinethylformamide, toluene, benzene, dioxane, methyl-sulphoxide are solvent, are catalyzer with the sodium hydride, synthetic through three steps, synthetic route is as follows:

The first step: 3, synthesizing of 3-diformazan sulfenyl-2-cyanoacrylate with after dehydrated alcohol, cyanoacetate, the dithiocarbonic anhydride mixing, controlled temperature is less than 20 ℃, begin to drip alcohol sodium solution, the dropping time is about 1h, after dropwising, stirring at normal temperature 8 hours, drip methyl-sulfate again, about 30min drips off, reflux 2.5h.To react the back system and pour in the water, standing over night gets the white needles solid, suction filtration, oven dry.Use normal hexane: ether=1: 1 recrystallization 2 times, 3,3-diformazan sulfenyl-2-cyanoacrylate.

Cyanoacetate: dithiocarbonic anhydride: methyl-sulfate: sodium ethylate=1: 1-1.5: 1-1.5: 2.0-3.0 (mol ratio)

Temperature of reaction: 10-100 ℃

Reaction times: 2-15h

This step is applicable to that all are above-mentioned 3,3-diformazan sulfenyl-2-cyanoacrylate synthetic.

Second step: 3-aromatic amino-3-methylthio group-2-cyanoacrylate synthetic

With 3,3-diformazan sulfenyl-2-cyanoacrylate, aromatic amine add in the there-necked flask, and fast 60% NaH are added, and drip DMF and toluene mixed solvent rapidly, and dropping temperature is controlled at below 10 ℃, behind the stirring at normal temperature 40h, react completely.Reaction system is poured in the frozen water, told water, slowly regulate pH with 10%HCl, separate out solid, ethyl alcohol recrystallization is used in oven dry, gets 3-aromatic amino-3-methylthio group-2-cyanoacrylate.

3,3-diformazan sulfenyl-2-cyanoacrylate: aromatic amine: sodium hydride=1: 1.0-2.0: 2.0-5.0 (mol ratio)

Temperature of reaction :-10-50 ℃

Reaction times: 20-72h

This step is applicable to the synthetic of all above-mentioned 3-aromatic amino-3-methylthio group-2-cyanoacrylates.

The 3rd step: 3-aromatic amino-3-alkyl (or fragrance) amine-2-cyanoacrylate synthetic

In 3-aromatic amino-3-methylthio group-2-cyanoacrylate and alkylamine or aromatic amine adding there-necked flask, add dehydrated alcohol and make solvent, reflux 2-36h, TLC follows the tracks of reaction, cooling, precipitation is after post separates, use the dehydrated alcohol recrystallization again, get 3-aromatic amino-3-alkyl (or fragrance) amine-2-cyanoacrylate.

3-aromatic amino-3-methylthio group-2-cyanoacrylate: aromatic amine or aliphatic amide=1: 0.8-1.6 (mol ratio)

Temperature of reaction: 60-100 ℃

Reaction times: 2-72h

This step is applicable to the synthetic of all above-mentioned 3-aromatic amino-3-alkyl (or fragrance) amine-2-cyanoacrylate.

Embodiment

Embodiment one, 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate synthetic (compound number is a):

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate:

In the 1000mL four-hole bottle, add dehydrated alcohol 400mL, ethyl cyanoacetate 34.0g (0.301mol), behind the dithiocarbonic anhydride 23.0g (0.303mol), controlled temperature is less than 20 ℃, begin to drip the sodium ethylate (0.610mol) of 360mL concentration 1.7M, the dropping time is about 1h, after dropwising, and stirring at normal temperature 8h, drip 38.5g methyl-sulfate (0.305mol) again, 30min dropwises, reflux 2.5h, and reaction finishes.Reaction system is poured in the 500mL water, and standing over night gets the white needles solid, suction filtration, oven dry.Use normal hexane: ether (1: 1) recrystallization 2 times, get the 36.7g white crystal, be 3,3-diformazan sulfenyl-2-cyanoacrylate, productive rate 56.2%, fusing point 53-54.5 ℃.

(2) 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate is synthetic:

3,3-diformazan sulfenyl-2-cyanoacrylate 2.17g (0.01mol), p-trifluoromethylaniline 1.61g (0.01mol), add in the 50mL there-necked flask, and the NaH (0.02mol) of 0.80g60% is added, drip 20mLDMF and 20mL toluene mixed solvent, dropping temperature is controlled at below 10 ℃, behind the stirring at normal temperature 40h, pour reaction system into the 100mL frozen water, tell water, slowly regulate pH with 10%HCL, yellowish solid is separated out, and ethyl alcohol recrystallization is used in oven dry, can get white crystal 2.25g, be 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate, yield 63.5%, fusing point 78-79 ℃.

Present embodiment aromatic amine applicatory comprises and contains fluorophenyl; pyrryl; furyl; tetrahydrofuran base; thienyl; thiazolyl; isothiazolyl; imidazolyl; pyrazolyl oxazolyl isoxazolyl; triazolyl; tetrazyl; thiadiazolyl group; pyridyl; morpholinyl; piperazinyl; triazinyl; piperidyl; pyridazinyl; pyrimidyl; purine radicals; pyrazinyl; naphthyl; quinolyl; isoquinolyl; phthalazinyl; naphthyridinyl; indyl; draw the azoles base; benzofuryl; benzimidazolyl-; benzothiazolyl; benzisothiazole base benzoxazolyl; the benzoisoxazole base; the benzopyrazoles base; quinazolyl; different quinazolyl; dibenzofuran group; the dibenzothiophene base; the bisbenzimidazole base; the dibenzo pyrimidyl; the dibenzopyridine base; carbazyl; and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom; (2) itrile group; (3) nitro; (4) C1-6 alkyl; C2-6 alkenyl or C2-6 alkynyl group; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (6) C1-6 alkoxyl group; C2-6 alkenyloxy or C2-6 chain oxy-acetylene; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (7) C1-6 alkylthio; C2-6 alkenyl thio or C2-6 alkynes sulfenyl; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (8) substituted carbonyl; described substituting group is selected from (i) C1-6 alkyl; (ii) amino; (iii) C1-6 alkylamino; (iv) C1-6 alkyl oxy; (v) C1-6 alkyl sulfenyl; (vi) C3-8 cycloalkyl; (9) can be by the amino of 1 or 2 each substituting groups replacement; described substituting group is selected from (i) C1-6 alkyl; (ii) C2-6 alkenyl; (iii) C2-6 alkynyl group; (iv) C1-6 alkyl sulphonyl; (v) C2-6 alkenyl alkylsulfonyl; (vi) C2-6 alkynyl group alkylsulfonyl; (vii) C1-6 alkyl-carbonyl; (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl; (10) C1-6 alkyl sulphonyl; (11) C2-6 alkenyl alkylsulfonyl; (12) C2-6 alkynyl group alkylsulfonyl; (13) C1-6 alkyl sulphinyl; (14) C2-6 alkenyl sulfinyl; (15) C2-6 alkynyl group sulfinyl; (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group.Also comprise the 4-trifluoromethyl, 2-chloro-4-picoline-3-base, 2,6-dichlor-4-trifluoromethyl phenyl, 2-fluoro-5-trifluoromethyl, 2-fluoro-3-trifluoromethyl, 2-bromo-5-fluorophenyl, 2-bromo-4, the 6-difluorophenyl, 5-methyl isoxzzole-3-base, 2-methoxyl group diphenylene-oxide-3-base, 1-tolimidazole-2-base, the 4-bromophenyl, 6-fluoro benzothiazole-2-base, 4-methylbenzothiazole-2-base, 6-methylbenzothiazole-2-base, 6-methoxyl group benzo thiazol-2-yl, 6-ethoxyl benzo thiazole-2-base, 2-bromo-4, the 6-3,5-dimethylphenyl, 4-bromo-2, the 6-dichlorophenyl, 4-bromo-2-chloro-phenyl-, 6-nitrobenzene thiazole-2-base, nicotinic acid-2-base, pyrazine-2-formic acid-3-base, 4-fluorobenzoic acid-2-base, 5-fluorobenzoic acid-2-base, 6-fluorobenzoic acid-2-base, 4,5-dimethoxybenzoic acid-2-base, 5-iodo-benzoic acid-2-base, 1-trifluoromethyl-2-fluorobenzene-5-base, 1-trifluoromethyl-5-bromobenzene-2-base, 1-trifluoromethyl-5-fluorobenzene-2-base, 1-trifluoromethyl-4-bromobenzene-3-base, 1-trifluoromethyl-3-bromobenzene-4-base, 5-bromopyridine-2-base, pyridine-2-formic acid-3-base, (S)-the Alpha-Methyl benzylamine, (R)-the Alpha-Methyl benzylamine.

Synthetic (compound number is b) of embodiment two, 3-(2, the 6-dichlor-4-trifluoromethyl) aniline-3-methylthio group-2-cyanoacrylate:

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate,

Synthetic as embodiment one (1) method and condition.

(2) 3-(2, the 6-dichlor-4-trifluoromethyl) aniline-3-methylthio group-2-cyanoacrylate is synthetic:

3,3-diformazan sulfenyl-2-cyanoacrylate 2.17g (0.01mol), 2,6-dichlor-4-trifluoromethyl aniline 2.30g (0.01mol) adds the 50mL there-necked flask, with NaH (0.02mol) adding of 0.80g60%, drip 20mLDMF and 20mL toluene mixed solvent afterwards, dropping temperature is controlled at below 10 ℃, behind the stirring at normal temperature 40h, reacts completely.Pour reaction system into the 100mL frozen water, tell water, slowly regulate pH with 10%HCl, yellowish solid is separated out, oven dry, use ethyl alcohol recrystallization, get white crystal 2.61g, be 3-(2, the 6-dichlor-4-trifluoromethyl) aniline-3-methylthio group-2-cyanoacrylate, yield 59.7%, fusing point 125.5-126.5 ℃.

Present embodiment aromatic amine applicatory comprises and contains fluorophenyl; pyrryl; furyl; tetrahydrofuran base; thienyl; thiazolyl; isothiazolyl; imidazolyl; pyrazolyl oxazolyl isoxazolyl; triazolyl; tetrazyl; thiadiazolyl group; pyridyl; morpholinyl; piperazinyl; triazinyl; piperidyl; pyridazinyl; pyrimidyl; purine radicals; pyrazinyl; naphthyl; quinolyl; isoquinolyl; phthalazinyl; naphthyridinyl; indyl; draw the azoles base; benzofuryl; benzimidazolyl-; benzothiazolyl; benzisothiazole base benzoxazolyl; the benzoisoxazole base; the benzopyrazoles base; quinazolyl; different quinazolyl; dibenzofuran group; the dibenzothiophene base; the bisbenzimidazole base; the dibenzo pyrimidyl; the dibenzopyridine base; carbazyl; and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom; (2) itrile group; (3) nitro; (4) C1-6 alkyl; C2-6 alkenyl or C2-6 alkynyl group; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (6) C1-6 alkoxyl group; C2-6 alkenyloxy or C2-6 chain oxy-acetylene; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (7) C1-6 alkylthio; C2-6 alkenyl thio or C2-6 alkynes sulfenyl; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (8) substituted carbonyl; described substituting group is selected from (i) C1-6 alkyl; (ii) amino; (iii) C1-C6 alkylamino; (iv) C1-6 alkyl oxy; (v) C1-6 alkyl sulfenyl; (vi) C3-8 cycloalkyl; (9) can be by the amino of 1 or 2 each substituting groups replacement; described substituting group is selected from (i) C1-6 alkyl; (ii) C2-6 alkenyl; (iii) C2-6 alkynyl group; (iv) C1-6 alkyl sulphonyl; (v) C2-6 alkenyl alkylsulfonyl; (vi) C2-6 alkynyl group alkylsulfonyl; (vii) C1-6 alkyl-carbonyl; (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl; (10) C1-6 alkyl sulphonyl; (11) C2-6 alkenyl alkylsulfonyl; (12) C2-6 alkynyl group alkylsulfonyl; (13) C1-6 alkyl sulphinyl; (14) C2-6 alkenyl sulfinyl; (15) C2-6 alkynyl group sulfinyl; (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group.Also comprise the 4-trifluoromethyl, 2-chloro-4-picoline-3-base, 2,6-dichlor-4-trifluoromethyl phenyl, 2-fluoro-5-trifluoromethyl, 2-fluoro-3-trifluoromethyl, 2-bromo-5-fluorophenyl, 2-bromo-4, the 6-difluorophenyl, 5-methyl isoxzzole-3-base, 2-methoxyl group diphenylene-oxide-3-base, 1-tolimidazole-2-base, the 4-bromophenyl, 6-fluoro benzothiazole-2-base, 4-methylbenzothiazole-2-base, 6-methylbenzothiazole-2-base, 6-methoxyl group benzo thiazol-2-yl, 6-ethoxyl benzo thiazole-2-base, 2-bromo-4, the 6-3,5-dimethylphenyl, 4-bromo-2, the 6-dichlorophenyl, 4-bromo-2-chloro-phenyl-, 6-nitrobenzene thiazole-2-base, nicotinic acid-2-base, pyrazine-2-formic acid-3-base, 4-fluorobenzoic acid-2-base, 5-fluorobenzoic acid-2-base, 6-fluorobenzoic acid-2-base, 4,5-dimethoxybenzoic acid-2-base, 5-iodo-benzoic acid-2-base, 1-trifluoromethyl-2-fluorobenzene-5-base, 1-trifluoromethyl-5-bromobenzene-2-base, 1-trifluoromethyl-5-fluorobenzene-2-base, 1-trifluoromethyl-4-bromobenzene-3-base, 1-trifluoromethyl-3-bromobenzene-4-base, 5-bromopyridine-2-base, pyridine-2-formic acid-3-base, (S)-the Alpha-Methyl benzylamine, (R)-the Alpha-Methyl benzylamine.

Embodiment three, 3-(synthetic (compound number is d) of the amine-3-methylthio group-2-cyanoacrylate of 4-methylbenzothiazole-2-):

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate,

Synthetic as embodiment one (1) method and condition.

(2) (the 4-methylbenzothiazole-2-) amine-3-methylthio group-2-cyanoacrylate is synthetic: 3 for 3-, 3-diformazan sulfenyl-2-cyanoacrylate 2.65g (0.012mol), 2-amino-4-methylbenzothiazole 2.0g (0.012mol) is incorporated in the 100mL there-necked flask.After adding 60%NaH0.96g (0.024mol), drip the mixed solvent of 25mL toluene and 25mLDMF afterwards, be no more than 20 ℃ with ice bath control dropping temperature, dropwise about 10min, behind the stirring at normal temperature 48h, TLC follows the tracks of reaction and finishes.Reaction system is poured in the 150mL frozen water, told water, the HCl solution with 10% splashes into, and has the milk yellow solid to separate out, and when system becomes clarification, stops to drip HCl.Suction filtration can get the milk yellow solid, oven dry, recrystallization twice in dehydrated alcohol, white crystal 2.5g, be 3-(amine-3-methylthio group-2-cyanoacrylate of 4-methylbenzothiazole-2-), yield 41.3%, fusing point 162.0-163.0 ℃.

Synthetic (compound number is f) of embodiment four, 3-p-trifluoromethylaniline-3-amino-2-cyanoacrylate:

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate,

Synthetic as embodiment one (1) method and condition.

(2) 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate is synthetic

Synthetic as embodiment one (2) method and condition.

(3) 3-p-trifluoromethylaniline-3-amino-2-cyanoacrylate is synthetic:

3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate 1.5g (0.00455mol) and 5mL ammoniacal liquor are placed the 50ml there-necked flask, add the 20ml dehydrated alcohol, reflux 5h.Cooling, the adularescent needle-like crystal is separated out, suction filtration, dehydrated alcohol recrystallization 2 times are used in oven dry, get needle-like white crystal 0.9g, are 3-p-trifluoromethylaniline-3-amino-2-cyanoacrylate, yield 72.6%, fusing point 193.5-195.0 ℃.

Present embodiment aliphatic amide applicatory or aromatic amine comprise C1-10 alkyl, C2-C10 alkenyl, C2-10 alkynyl group, C1-10 alkyl sulphonyl, C2-10 alkenyl alkylsulfonyl, C2-10 alkynyl group alkylsulfonyl, C1-10 alkyl-carbonyl, C2-10 alkenyl carbonyl, C2-10 alkynyl group carbonyl, R ₃Be the C1-10 alkyl, the C3-8 cycloalkyl, the fluoro aromatic group of C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom, (2) itrile group, (3) nitro, (4) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group.

Synthetic (compound number is i) of embodiment five, 3-p-trifluoromethylaniline-3-Isopropylamine-2-cyanoacrylate:

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate,

Synthetic as embodiment one (1) method and condition.

(2) 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate is synthetic,

Synthetic as embodiment one (2) method and condition.

(3) 3-p-trifluoromethylaniline-3-Isopropylamine-2-cyanoacrylate is synthetic:

3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate 1.5g (0.00455mol) and 0.292g Isopropylamine (0.00478mol) are placed the 50ml there-necked flask, add the 20ml dehydrated alcohol, reflux 8h.Precipitation gets yellow thick liquid, adds 30ml water, stir, have solid to separate out, suction filtration gets yellow powder, oven dry, with dehydrated alcohol recrystallization 2 times, block white crystal 1.0g, be 3-p-trifluoromethylaniline-3-Isopropylamine-2-cyanoacrylate, yield 58.6%, fusing point 100.5-102.0 ℃.

Present embodiment aliphatic amide applicatory or aromatic amine comprise C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl group, C1-10 alkyl sulphonyl, C2-10 alkenyl alkylsulfonyl, C2-10 alkynyl group alkylsulfonyl, C1-10 alkyl-carbonyl, C2-10 alkenyl carbonyl, C2-10 alkynyl group carbonyl, R ₃Be the C1-10 alkyl, the C3-8 cycloalkyl, the fluoro aromatic group of C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom, (2) itrile group, (3) nitro, (4) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group.

Synthetic (compound number is j) of embodiment six, 3-p-trifluoromethylaniline-3-benzylamine-2-cyanoacrylate:

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate,

Synthetic as embodiment one (1) method and condition.

(2) 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate is synthetic,

Synthetic as embodiment one (2) method and condition.

(3) 3-p-trifluoromethylaniline-3-benzylamine-2-cyanoacrylate is synthetic:

3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate 1.5g (0.00455mol) and 0.51g benzylamine (0.00478mol) are placed the 50mL there-necked flask, add the 20mL dehydrated alcohol, reflux 8h, TLC follow the tracks of reaction and finish.Cooling has crystal to separate out, and suction filtration gets micro-yellow powder, oven dry, and recrystallization 2 times gets the needle-like white solid, is 3-p-trifluoromethylaniline-3-benzylamine-2-cyanoacrylate, yield 71.5%, fusing point 144-146 ℃.

Synthetic (compound number is k) of embodiment seven, 3-p-trifluoromethylaniline-3-(S)-Alpha-Methyl benzylamine-2-cyanoacrylate:

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate,

Synthetic as embodiment one (1) method and condition.

(2) 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate is synthetic,

Synthetic as embodiment one (2) method and condition.

(3) 3-p-trifluoromethylaniline-3-(S)-Alpha-Methyl benzylamine-2-cyanoacrylate is synthetic:

With 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate 1.2g (0.036mol) and 0.44g (S)-body-Alpha-Methyl benzylamine, add the 20mL dehydrated alcohol, behind the backflow 10h, precipitation gets yellow thick liquid.With sherwood oil: ethyl acetate (2.5: 1) is that eluent is crossed silicagel column, obtains white crystal, is 3-p-trifluoromethylaniline-3-(S)-Alpha-Methyl benzylamine-2-cyanoacrylate, yield 62.5%, fusing point 145-147 ℃, [α] _D ¹⁵=-12.5 ° (solvent is an acetone).

Synthetic (compound number is 1) of embodiment eight, 3-p-trifluoromethylaniline-3-(R)-Alpha-Methyl benzylamine-2-cyanoacrylate:

Synthesizing of (1) 3,3-diformazan sulfenyl-2-cyanoacrylate, synthetic as embodiment one (1) method and condition.

(2) 3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate is synthetic, synthetic as embodiment one (2) method and condition.

(3) 3-p-trifluoromethylaniline-3-(R)-Alpha-Methyl benzylamine-2-cyanoacrylate is synthetic, as synthetic as embodiment seven (3) methods and condition.Yield 61.5%, fusing point are 136-138 ℃, [α] _D ¹⁵=+12.5 ° (solvent is an acetone).

Utilize similar synthetic method, under the identical situation of the first step, select distinct fragrance amine for use, select for use different aliphatic amide synthetic cyanoacrylate derivatives as shown in table 1 in the 3rd step in second step.The cyanoacrylate compound proton nmr spectra of partial synthesis ( ¹H NMR) data are as shown in table 1, and physico-chemical property and ultimate analysis data are as shown in table 2, and infrared spectra (IR) data are as shown in table 3, carbon-13 nmr spectra ( ¹³C NMR) data are as shown in table 4, and mass spectrum (MS) data are as shown in table 5.

The proton nmr spectra data of table 1 part institute synthetic compound

The physico-chemical property and the ultimate analysis of table 2 part institute synthetic compound

Physical Yield Elemental?analysis(Calcd.，％)

Compd. m.p./℃

state ％ C H N

a White?crystal 78～79 63.5 50.42(50.69) 3.61(3.94) 8.10(8.48)

b White?crystal 125.5～126.5 59.7 42.00(42.11) 2.52(2.76) 7.00(7.02)

c White?crystal 113～114.5 61.5 50.00(50.08) 4.37(4.49) 13.21(13.48)

d White?crystal 162～163 41.3 53.25(54.05) 4.45(4.50) 12.33(12.61)

e White?crystal 105～106 42.3 57.36(57.52) 5.73(5.52) 9.69(9.58)

f White?crystal 193.5～194.5 72.6 52.13(52.17) 3.85(4.01) 13.9(14.05)

g White?crystal 95.5～96.5 58.1 56.17(56.30) 5.20(5.28) 12.30(12.32)

h White?solid 105～106 45.0 56.79(57.46) 5.71(5.63) 11.54(11.83)

i White?solid 100.5～102 58.6 56.36(56.30) 4.91(5.27) 12.39(12.31)

j White?solid 144～146 71.5 61.12(61.09) 4.52(4.62) 10.61(10.79)

k White?crystal 145～147 62.5 61.80(61.90) 4.28(4.50) 9.91(9.95)

l White?crystal 136～138 61.5 61.74(61.90) 4.18(4.50) 10.09(9.99)

m White?crystal 139～141 33.6 52.25(52.40) 3.40(3.49) 9.01(9.17)

n White?crystal 138.5～141.5 54.7 55.51(55.81) 5.50(5.89) 17.24(17.36)

o White?crystal 143～145 74.5 57.00(57.06) 6.18(6.24) 16.39(16.64)

p White?crystal 140～142 56.0 61.00(61.53) 5.07(5.12) 14.58(15.11)

q White?crystal 107～109 63.1 55.31(55.81) 5.62(5.89) 17.16(17.36)

The IR data of table 3 part institute synthetic compound

Compd. IR，ν _max/cm ^-1

a 3005.1，2208.4，1653.0，1546.9，1537.2，1396.4，1377.1，1313.5，1307.7，1269.1，1172.7，

1124.5，1118.7，1024.2，881.4，810.1，675.0

b 3319.4，3061.0，3028.2，2916.3，2872.0，1625.9，1610.5，1571.9，1533.4，1492.9，1471.6，

1452.4，1419.6，1244.0，1060.8，790.3，696.3，669.3

c 3284.7，2200.78，1637.5，1620.2，1608.6，1585.4，1531.4，1458.1，1446.6，1431.1，1386.8，

1369.4，1298.0，1269.1，1120.6，1109.0，1085.9，779.2

d 2987.7，2214.2，1658.7，1593.2，1568.1，1498.8，1471.6，1402.2，1384.8，1371.3，1309.6，

1288.2，1257.5，1234.4，1259.2，1024.2，877.6，798.5，783.1，746.4

f 3204.7，2976.1，2200.7，1635.6，1620.2，1608.6，1585.4，1531.4，1458.1，1446.6，1492.2，

1386.8，1369.4，1298.0，1269.1，1120.6，1109.0，1085.9，779.2

g 3213.4，2995.4，2970.3，2200.7，1651.0，1587.4，1537.2，1444.6，1427.3，1384.8，1369.4，

1294.2，1274.9，1244.0，1226.7，1188.1，1165.0，1107.1，1089.7，1002.9，873.7，775.3，734.8，

698.2

h 3425.5，3304.1，3194.1，3053.3，1627.9，1589.3，1548.8，1473.6，1438.9，1417.6，1375.2，

1294.2，1112.9，1085.9，858.3，819.7，655.8，526.5

i 2204.6，1668.4，1583.5，?1531.4，1479.4，1440.8，1408.0，1369.4，1348.2，1303.8，1273.0，

1253.7，1170.7，1157.2，1026.1，701.1

j 3012.8，2997.3，2980.0，2937.5，2204.6，1668.4，1558.5，1531.4，1479.4，1436.9，1408.0，

1369.4，1348.2，1303.8，1273.0，1253.7，1186.2，1165.0，1157.2，1026.1，781.1

k 3257.7，2196.9，1666.5，1620.2，1595.1，1543.6，144g.5，1371.3，1354.0，1327.0，1284.5，

1255.6，1186.2，1166.9，1114.8，1097.5，1066.6，763.8，702.0，，，

l 3257.7，2196.9，1666.5，1620.2，1595.1，1543.1，1448.5，1371.3，1354.0，1327.0，1284.5，

1255.6，1186.2，1166.9，1114.8，1097.5，1066.6，844.8，763.8，702.0，549.7

m 2200.7，1654.9，1608.6，1581.6，1521.8，1458.1，1415.7，1377.1，1323.1，1313.5，1284.5，

1249.8，1165.0，1103.2，1066.6，837.1

n 2196.9，1666.5，1600.2，1595.1，1448.5，1327.0，1284.5，1255.6，1166.9，1114.8，1097.5，1066.6

o 2208.4，1653.0，1543.0，1396.4，1377.1，1311.5，1269.1，1232.5，1211.3，1172.7，1124.5，

1024.2，881.4

p 3197.9，3107.3，3030.1，2985.8，2191.1，1662.6，1608.6，1570.0，1527.6，1506.4，1481.3，

1456.2，1436.9，1386.7，11371.3，1325.1，1294.2，1276.8，1207.4，1168.8，1132.2，1114.8，

1105.2，1000.14，885.3，775.3，759.9

Table 4 part institute synthetic compound ¹³C NMR data

Compd. ¹³C?NMR，δ(CDCl ₃)

a 206.18，127.37，125.66，117.12，61.77，17.25，14.56

b 172.17，167.62，136.85，135.62，132.03，131.69，125.66，125.62，125.58，123.48，

120.76，116.69，79.68，61.66，18.22，14.15

c 172.62，167.71，150.06，148.78，148.18，131.49，124.77，116.93，61.32，18.26，

17.89，14.08

d 166.52，156.64，127.35，125.01，118.46，116.29，83.92，77.32，77.00，76.68，

62.15，18.98，18.05，14.17

e 206.25，163.63，144.93，137.67，117.50，111.60，61.53，53.95，17.52，14.55

f 169.36，161.83，161.26，138.40，127.48，127.44，127.40，125.18，118.82，60.32，

14.47

g 169.33，162.15，126.71，122.89，120.42，60.37，47.37，22.83，14.44，11.11

h 169.33，162.16，142.37，126.78，122.86，120.51，60.40，45.32，31.45，19.65，

14.45，13.46

j 169.14，161.17，137.35，136.90，134.38，129.29，128.96，128.66，127.63，127.45，

125.84，125.80，123.96，121.23，117.18，59.40，57.34，46.22，14.36

k 128.94，127.90，126.66，126.62，125.25，121.23，60.59，54.68，24.22，14.41

l 161.60，141.93，141.52，128.93，127.88，126.60，126.64，125.25，123.18，121.21，

118.67，63.10，60.57，54.68，24.20，23.73，14.40

m 168.41，161.27，143.63，137.41，128.73，127.59，127.25，126.38，126.35，120.30，

118.59，61.02，59.52，46.79，14.43

n 170.63，163.24，148.36，147.62，125.11，60.19，18.39，14.44

o 125.07，60.12，18.37，14.41，13.36

p 129.01，128.26，126.81，125.05，60.34，18.29，14.42

q 149.21，148.17，132.56，125.43，60.68，17.99，14.27

Leading ion among the EIMS of table 5 part institute synthetic compound

Compd. M ⁺Main fragmention

a 330 311，283，270，255，237，212，198，184，160，145，125，111，95，75，57，43，

29.18

b 398 383，363，351，335，323，305，291，282，263，252，240，227，213，194，178，

166，155，143，130，111，97，86，68，57，45，29，18

c 311 296，288，276，264，256，248，236，226，218，204，193，184，169，154，140，

129，117，109，99，90，75，65，52，39，29，18

g 341 326，313，298，287，273，254，237，226，210，199，187，174，161，145，135，

125，111，95，85，69，58，43，29，18

h 355 340，326，312，298，287，273，263，254，241，226，210，199，187，174，161，

145，135，125，111，93，83，68，57，41，29，18

i 341 332，322，312，296，282，273，264，254，237，226，210，199，187，172，161，

145，134，125，111，102，93，83，68，58，43，29，18

j 389 389，370，358，344，328，316，299，299，288，276，264，251，235，223，210，

187，172，155，142，128，106，91，77，65，43，29，17

k 403 381，369，358，344，333，317，293，288，263，256，242，226，210，199，187，

172，161，145，133，122，105，93，79，63，43，29，15

l 403 384，369，358，344，333，314，299，288，273，253，242，226，210，199，187，

172，161，145，133，120，105，93，77，57，43，29，18

m 458?422，412，394，378，356，323，298，286，272，255，242，229，215，205，194，

181，166，155，143，128，116，106，91，77，65，55，43，29，18

p 370 335，323，307，291，279，263，247，236，220，205，191，180，167，149，129，

117，106，91，80，69，57，43，29，18

Embodiment nine, compound b suppress to measure to the propagation of PC3 prostate cancer cell strain

Test method

Medicine is mixed with each concentration, every concentration triplicate with the DMSO dissolving; Suspension 4 * 10 will be made behind the PC3 cell dissociation ⁴Individual/ml, get 10ml and add in the big culture dish, treat that 24hr is adherent after, dosing is handled; Get 2 wares behind the 24hr at random and take pictures, the record cell state; The former substratum of sucking-off changes pastille substratum (10%FBS 1640) and handles 72hr; Add the 1.5ml pancreatin, add former pastille substratum behind the digestion 4min and stop digestion, beat and spare, the counting cells number is averaged, and calculates inhibiting rate.

Test-results

After tested, when the compound b drug concentration is 10 μ g/mL the PC3 cell proliferation inhibition rate is reached 81.35%, show good anti-cancer activity.

Embodiment ten, employing MTT method are measured compound b and are suppressed the PC3 cell-proliferation activity

Test method

With the PC3 cell inoculation in 96 hole enzyme plates, 2000 cells in every hole, cultivate 24h under the normal condition, add the processing factor, establish blank and solvent control, 4 every group parallel, continue to cultivate 96h (48h changes liquid once), add 5mg/mlMTT20 μ l and cultivate 4h, on microplate reader, measure the OD value, make reference with the solvent control group at last and calculate the inhibiting rate mapping.

Test-results is seen Fig. 1, and compound b suppresses PC3 cell-proliferation activity (mtt assay mensuration):

From the graph as can be seen, compound b can suppress PC3 cell proliferation about 70% under 9.5 μ g/ml concentration.

Embodiment 11, compound k suppress to measure to the propagation of PC3 prostate cancer cell strain

Test method is with embodiment nine.

Test-results

After tested, when compound k drug concentration is 20 μ g/mL the PC3 cell proliferation inhibition rate is reached 88.04%, show good anti-cancer activity.

Embodiment 12, compound i and j suppress the determination of activity of phosphorylation cell in vitro

Test-results is seen Fig. 2, Fig. 3 and Fig. 4 respectively.

Fig. 2 compound i and j suppress PDGF inductive l cell strain NIH3T3 cell ERK protein phosphorylation (20 μ g/ml);

Fig. 3 compound i suppresses PDGF inductive l cell strain NIH3T3 cell ERK protein phosphorylation concentration gradient;

Fig. 4 compound j suppresses PDGF inductive l cell strain NIH3T3 cell ERK protein phosphorylation concentration gradient.

By Fig. 2, Fig. 3 and Fig. 4 as can be known, compound i and j have the activity that suppresses P44/42 MAPK phosphorylation under drug concentration 20 μ g/ml.

Embodiment 13, compound b are to the inhibition activity test of tobacco mosaic disease (TMV)

Test method

With the medicament and isopyknic viral TMV juice mixing passivation 30min of 500mg/L, a frictional inoculation Nicotiana glutinosa left side half leaf, right half leaf of solvent and viral TMV juice combined inoculation.Write down withered spot number after 3 days.The calculation formula of inhibiting rate is as follows:

Test-results

After tested, be 54.0% to the TMV inhibiting rate when compound b drug concentration is 1.26mmol/L, be better than contrasting medicament virus of A, virazole, show good anti-phytoviral activity.Embodiment 14, compound n are to the inhibition activity test of tobacco mosaic disease (TMV)

Test method is with embodiment 13.

Test-results

After tested, be 20.0% to the TMV inhibiting rate when compound n drug concentration is 1.55mmol/L, show certain anti-phytoviral activity.

The embodiment of the invention is aided with explanation technical scheme of the present invention, but the content of embodiment is not limited thereto.

Claims

1, a kind of medicine that is used for antitumor and Antiphytoviral is characterized in that this medicine is the cyanoacrylate derivative, by the compound of following general formula:

R wherein ₁Be the C1-6 alkyl;

R ₂When being respectively hydrogen, C1-10 alkyl, C3-8 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl group, C1-10 alkyl sulphonyl, C2-10 alkenyl alkylsulfonyl, C2-10 alkynyl group alkylsulfonyl, C1-10 alkyl-carbonyl, C2-10 alkenyl carbonyl, C2-10 alkynyl group carbonyl, R ₃Be respectively the fluoro aromatic group of C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) hydroxyl, (2) halogen atom, (3) itrile group, (4) nitro, (5) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (7) C1-6 alkylthio, C2-6 alkenyl thio or C2-6 alkynes sulfenyl, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (8) substituted carbonyl, described substituting group is selected from (i) C1-6 alkyl, (ii) amino, (iii) C1-6 alkylamino, (iv) C1-6 alkyl oxy, (v) C1-6 alkyl sulfenyl, (vi) C3-8 cycloalkyl, (9) can be by the amino of 1 or 2 each substituting groups replacement, described substituting group is selected from (i) C1-6 alkyl, (ii) C2-6 alkenyl, (iii) C2-6 alkynyl group, (iv) C1-6 alkyl sulphonyl, (v) C2-6 alkenyl alkylsulfonyl, (vi) C2-6 alkynyl group alkylsulfonyl, (vii) C1-6 alkyl-carbonyl, (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl, (10) C1-6 alkyl sulphonyl, (11) C2-6 alkenyl alkylsulfonyl, (12) C2-6 alkynyl group alkylsulfonyl, (13) C1-6 alkyl sulphinyl, (14) C2-6 alkenyl sulfinyl, (15) C2-6 alkynyl group sulfinyl, (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group; More than remove R ₂And R ₃Be hydrogen, C1-10 alkyl, C3-8 cycloalkyl or its mutual combination simultaneously.

R ₃When being respectively hydrogen, C1-10 alkyl, C3-8 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl group, C1-10 alkyl sulphonyl, C2-10 alkenyl alkylsulfonyl, C2-10 alkynyl group alkylsulfonyl, C1-10 alkyl-carbonyl, C2-10 alkenyl carbonyl, C2-10 alkynyl group carbonyl, R ₂Be respectively the fluoro aromatic group of C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) hydroxyl, (2) halogen atom, (3) itrile group, (4) nitro, (5) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (7) C1-6 alkylthio, C2-6 alkenyl thio or C2-6 alkynes sulfenyl, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (8) substituted carbonyl, described substituting group is selected from (i) C1-6 alkyl, (ii) amino, (iii) C1-6 alkylamino, (iv) C1-6 alkyl oxy, (v) C1-6 alkyl sulfenyl, (vi) C3-8 cycloalkyl, (9) can be by the amino of 1 or 2 each substituting groups replacement, described substituting group is selected from (i) C1-6 alkyl, (ii) C2-6 alkenyl, (iii) C2-6 alkynyl group, (iv) C1-6 alkyl sulphonyl, (v) C2-6 alkenyl alkylsulfonyl, (vi) C2-6 alkynyl group alkylsulfonyl, (vii) C1-6 alkyl-carbonyl, (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl, (10) C1-6 alkyl sulphonyl, (11) C2-6 alkenyl alkylsulfonyl, (12) C2-6 alkynyl group alkylsulfonyl, (13) C1-6 alkyl sulphinyl, (14) C2-6 alkenyl sulfinyl, (15) C2-6 alkynyl group sulfinyl, (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group; More than remove R ₂And R ₃Be hydrogen, C1-10 alkyl, C3-8 cycloalkyl or its mutual combination simultaneously.

R ₂, R ₃Be respectively the fluoro aromatic group of C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) hydroxyl, (2) halogen atom, (3) itrile group, (4) nitro, (5) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (7) C1-6 alkylthio, C2-6 alkenyl thio or C2-6 alkynes sulfenyl, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (8) substituted carbonyl, described substituting group is selected from (i) C1-6 alkyl, (ii) amino, (iii) C1-6 alkylamino, (iv) C1-6 alkyl oxy, (v) C1-6 alkyl sulfenyl, (vi) C3-8 cycloalkyl, (9) can be by the amino of 1 or 2 each substituting groups replacement, described substituting group is selected from (i) C1-6 alkyl, (ii) C2-6 alkenyl, (iii) C2-6 alkynyl group, (iv) C1-6 alkyl sulphonyl, (v) C2-6 alkenyl alkylsulfonyl, (vi) C2-6 alkynyl group alkylsulfonyl, (vii) C1-6 alkyl-carbonyl, (viii) C2-6 alkenyl carbonyl (ix) C2-6 alkynyl group carbonyl, (10) C1-6 alkyl sulphonyl, (11) C2-6 alkenyl alkylsulfonyl, (12) C2-6 alkynyl group alkylsulfonyl, (13) C1-6 alkyl sulphinyl, (14) C2-6 alkenyl sulfinyl, (15) C2-6 alkynyl group sulfinyl, (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group; More than remove R ₂And R ₃Be hydrogen, C1-10 alkyl, C3-8 cycloalkyl or its mutual combination simultaneously;

X is NH, S, O, SO or SO2.

2, a kind of medicine that is used for antitumor and Antiphytoviral according to claim 1, R in its compound general formula ₃Fluoro aromatic group for C5-14, contain 1 or a plurality of N of being selected from, O, S, the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom, (2) itrile group, (3) nitro, (4) C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group, (6) C1-6 alkoxyl group, C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group.

3, a kind of medicine that is used for antitumor and Antiphytoviral according to claim 2, R in its compound general formula ₂Be hydrogen; the C1-10 alkyl; the C3-8 cycloalkyl; the C2-10 alkenyl; the C2-10 alkynyl group; the C1-10 alkyl sulphonyl; C2-10 alkenyl alkylsulfonyl; C2-10 alkynyl group alkylsulfonyl; the C1-10 alkyl-carbonyl; the C2-10 alkenyl carbonyl; C2-10 alkynyl group carbonyl; the fluoro aromatic group of C5-14; contain 1 or a plurality of N of being selected from; O; S; the heteroatomic C5-14 hetero-aromatic ring group of SO and SO2; and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group replaces: (1) halogen atom; (2) itrile group; (3) nitro; (4) C1-6 alkyl; C2-6 alkenyl or C2-6 alkynyl group; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (6) C1-6 alkoxyl group; C2-6 alkenyloxy or C2-6 chain oxy-acetylene, wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group.

4, a kind of medicine that is used for antitumor and Antiphytoviral according to claim 3, R in its compound general formula ₁Be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, n-pentyl, isopentyl, tert-pentyl, neo-pentyl.

5, according to any described a kind of medicine that is used for antitumor and Antiphytoviral among the claim 1-3, X is NH, S, O in its compound general formula.

6, a kind of medicine that is used for antitumor and Antiphytoviral according to claim 1, R in its compound general formula ₂Or R ₃For containing fluorophenyl, pyrryl, furyl, tetrahydrofuran base, thienyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl oxazolyl isoxazolyl, triazolyl, tetrazyl, thiadiazolyl group, pyridyl, morpholinyl, piperazinyl, triazinyl, piperidyl, pyridazinyl, pyrimidyl, purine radicals, pyrazinyl, naphthyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, indyl, draw the azoles base, benzofuryl, benzimidazolyl-, benzothiazolyl, benzisothiazole base benzoxazolyl, the benzoisoxazole base, the benzopyrazoles base, quinazolyl, different quinazolyl, dibenzofuran group, the dibenzothiophene base, the bisbenzimidazole base, the dibenzo pyrimidyl, the dibenzopyridine base, carbazyl, and can independently be selected from following substituent group by one or more on the above-mentioned cyclic group and replace; (1) halogen atom; (2) itrile group; (3) nitro; (4) C1-6 alkyl; C2-6 alkenyl or C2-6 alkynyl group; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (6) C1-6 alkoxyl group; C2-6 alkenyloxy or C2-6 chain oxy-acetylene; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (7) C1-6 alkylthio; C2-6 alkenyl thio or C2-6 alkynes sulfenyl; wherein each group all can be replaced by at least one or a plurality of halogen atom substituting group; (8) substituted carbonyl; described substituting group is selected from (i) C1-6 alkyl; (ii) amino; (iii) C1-6 alkylamino; (iv) C1-6 alkyl oxy; (v) C1-6 alkyl sulfenyl; (vi) C3-8 cycloalkyl; (9) can be by the amino of 1 or 2 each substituting groups replacement; described substituting group is selected from (i) C1-6 alkyl; (ii) C2-6 alkenyl; (iii) C2-6 alkynyl group, (iv) C1-6 alkyl sulphonyl, (v) C2-6 alkenyl alkylsulfonyl; (vi) C2-6 alkynyl group alkylsulfonyl; (vii) C1-6 alkyl-carbonyl, (viii) C2-6 alkenyl carbonyl, (ix) C2-6 alkynyl group carbonyl; (10) C1-6 alkyl sulphonyl; (11) C2-6 alkenyl alkylsulfonyl, (12) C2-6 alkynyl group alkylsulfonyl, (13) C1-6 alkyl sulphinyl; (14) C2-6 alkenyl sulfinyl; (15) C2-6 alkynyl group sulfinyl, (16) formyl radical, (17) C3-8 cycloalkyl or C3-8 cycloalkenyl group.

7, according to any described a kind of medicine that is used for antitumor and Antiphytoviral among the claim 1-6, R in its compound general formula ₂Or R ₃Be the 4-trifluoromethyl, 2-chloro-4-picoline-3-base, 2,6-dichlor-4-trifluoromethyl phenyl, 2-fluoro-5-trifluoromethyl, 2-fluoro-3-trifluoromethyl, 2-bromo-5-fluorophenyl, 2-bromo-4, the 6-difluorophenyl, 5-methyl isoxzzole-3-base, 2-methoxyl group diphenylene-oxide-3-base, 1-tolimidazole-2-base, the 4-bromophenyl, 6-fluoro benzothiazole-2-base, 4-methylbenzothiazole-2-base, 6-methylbenzothiazole-2-base, 6-methoxyl group benzo thiazol-2-yl, 6-ethoxyl benzo thiazole-2-base, 2-bromo-4, the 6-3,5-dimethylphenyl, 4-bromo-2, the 6-dichlorophenyl, 4-bromo-2-chloro-phenyl-, 6-nitrobenzene thiazole-2-base, nicotinic acid-2-base, pyrazine-2-formic acid-3-base, 4-fluorobenzoic acid-2-base, 5-fluorobenzoic acid-2-base, 6-fluorobenzoic acid-2-base, 4,5-dimethoxybenzoic acid-2-base, 5-iodo-benzoic acid-2-base, 1-trifluoromethyl-2-fluorobenzene-5-base, 1-trifluoromethyl-5-bromobenzene-2-base, 1-trifluoromethyl-5-fluorobenzene-2-base, 1-trifluoromethyl-4-bromobenzene-3-base, 1-trifluoromethyl-3-bromobenzene-4-base, 5-bromopyridine-2-base, pyridine-2-formic acid-3-base, (S)-the Alpha-Methyl benzylamine, (R)-the Alpha-Methyl benzylamine.

8, a kind of medicine that is used for antitumor and Antiphytoviral according to claim 1 is characterized in that the compound of partial synthesis is as follows:

A.3-p-trifluoromethylaniline-3-methylthio group-2-cyanoacrylate

B.3-(2, the 6-dichlor-4-trifluoromethyl) aniline-3-methylthio group-2-cyanoacrylate

C.3-methylthio group-3-(2-chloro-4-picoline) amino-2-cyanoacrylate

D.3-(amine-3-methylthio group-2-the cyanoacrylate of 4-methylbenzothiazole-2-)

E.3-(amine-3-methylthio group-2-the cyanoacrylate of 2-dioxy yl pyridines-5-)

F.3-p-trifluoromethylaniline-3-amino-2-cyanoacrylate

G.3-p-trifluoromethylaniline-3-Tri N-Propyl Amine-2-cyanoacrylate

H.3-to trifluoromethyl-3-n-Butyl Amine 99-2-cyanoacrylate

I.3-p-trifluoromethylaniline-3-Isopropylamine-2-cyanoacrylate

J.3-p-trifluoromethylaniline-3-benzylamine-2-cyanoacrylate

K.3-p-trifluoromethylaniline-3-(S)-Alpha-Methyl benzylamine-2-cyanoacrylate

L.3-p-trifluoromethylaniline-3-(R)-Alpha-Methyl benzylamine-2-cyanoacrylate

M.3-to trifluoromethyl benzylamine-3-benzylamine-2-cyanoacrylate

N.3-(2-chloro-4-methyl-3-aminopyridine)-3-Tri N-Propyl Amine-2-cyanoacrylate

O.3-(2-chloro-4-methyl-3-aminopyridine)-3-n-Butyl Amine 99-2-cyanoacrylate

P.3-(2-chloro-4-methyl-3-aminopyridine)-3-benzylamine-2-cyanoacrylate

Q.3-(2-chloro-4-methyl-3-aminopyridine)-3-Isopropylamine-2-cyanoacrylate

9, be it as anti-tumor drug or as the medicine of plant antiviral agent according to any described compound among the claim 1-8.

10, a kind of preparation method who is used for the medicine of antitumor and Antiphytoviral according to claim 1, it is characterized in that with dithiocarbonic anhydride, cyan-acetic ester, methyl-sulfate, aromatic amine be raw material, with ethanol, Virahol, dehydrated alcohol, N, dinethylformamide, toluene, benzene, dioxane, methyl-sulphoxide are solvent, with the sodium hydride is catalyzer, synthetic through three steps:

The first step: 3,3-diformazan sulfenyl-2-cyanoacrylate synthetic

After dehydrated alcohol, cyanoacetate, dithiocarbonic anhydride mixing, controlled temperature begins to drip alcohol sodium solution less than 20 ℃, and the dropping time is about 1h, and after dropwising, stirring at normal temperature 8 hours drips methyl-sulfate again, and about 30min drips off, reflux 2.5h.To react the back system and pour in the water, standing over night gets the white needles solid, suction filtration, oven dry.Use normal hexane: ether=1: 1 recrystallization 2 times, 3,3-diformazan sulfenyl-2-cyanoacrylate.

Second step: 3-aromatic amino-3-methylthio group-2-cyanoacrylate synthetic