CN106146367B - Allyl sulfenyl amino 1,4-benzoquinone class compound, it is prepared and application - Google Patents
Allyl sulfenyl amino 1,4-benzoquinone class compound, it is prepared and application Download PDFInfo
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- CN106146367B CN106146367B CN201510197566.2A CN201510197566A CN106146367B CN 106146367 B CN106146367 B CN 106146367B CN 201510197566 A CN201510197566 A CN 201510197566A CN 106146367 B CN106146367 B CN 106146367B
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- 0 *C=C(*)CSC(C(C=C1N(*)*)=O)=CC1=O Chemical compound *C=C(*)CSC(C(C=C1N(*)*)=O)=CC1=O 0.000 description 2
- HEGRKVAVYZWMKW-UHFFFAOYSA-N C=CCSC(C(C=C1NCC2OCCC2)=O)=CC1=O Chemical compound C=CCSC(C(C=C1NCC2OCCC2)=O)=CC1=O HEGRKVAVYZWMKW-UHFFFAOYSA-N 0.000 description 1
- UIVVIEDRNZIWHV-UHFFFAOYSA-N C=CCSC(C(C=C1NCCCl)=O)=CC1=O Chemical compound C=CCSC(C(C=C1NCCCl)=O)=CC1=O UIVVIEDRNZIWHV-UHFFFAOYSA-N 0.000 description 1
- GRVUPYOFICRKFZ-HWKANZROSA-N CC(CNC(C(C=C1SC/C=C/c2cccnc2)=O)=CC1=O)O Chemical compound CC(CNC(C(C=C1SC/C=C/c2cccnc2)=O)=CC1=O)O GRVUPYOFICRKFZ-HWKANZROSA-N 0.000 description 1
- OKFFXAPUPLSBDP-UHFFFAOYSA-N CSCCCNC(C(C=C1SCC=C)=O)=CC1=O Chemical compound CSCCCNC(C(C=C1SCC=C)=O)=CC1=O OKFFXAPUPLSBDP-UHFFFAOYSA-N 0.000 description 1
Abstract
Allyl sulfenyl amino 1,4-benzoquinone class compound, it is prepared and application, the present invention relates to the compound shown in logical formula (I) or its pharmaceutically acceptable salt or solvate, further relates to the preparation method of above-claimed cpd and its purposes in terms of preparing for anti-tumor drug.
Description
Technical field
The present invention relates to a kind of compound with antitumor activity.Specifically, the present invention relates to logical formula (I) compound
And preparation method thereof, further relate to purposes of the logical formula (I) compound in anti-tumor aspect.
Background technology
Due to the special structure and properties of quinones, its potential medical value and mechanism of action be constantly found,
Research and announcement, important role is play in human health and disease treatment is maintained.However, because quinone is in itself with higher
Oxidation-reduction quality, biological alkanisation etc., multiple side effect easily is produced to body；Stronger lipophilicity influences the hair of its effect
Wave；Tumour cell, pathogenic microorganism etc. are also quinones (candidate) drug research urgent problem to be solved to its caused tolerance.
S-/N- substitutes 1,4-benzoquinone class compound to be cured as a kind of important p-benzoquinone derivative in organic chemical industry, life
The fields such as medicine, disease treatment have a wide range of applications.However, S- substitution 1,4-benzoquinone class compound synthesis in, it is monosubstituted and
The polysubstituted more difficult control of product, and more to be not easy to obtain, irritant and toxicity mercaptan is used as sulphur source.For N, S- bis- takes
Less for the study on the synthesis of 1,4-benzoquinone class compound, only synthetic method step is more, reaction is more complicated.Many N, S- bis- take
Activity, toxicity for 1,4-benzoquinone class compound still fail the requirement for reaching drug candidate, and the research to its mechanism of action is also inadequate
Deeply.
The content of the invention
To solve above-mentioned problem, the inventors found that a kind of logical formula (I) compound with antitumor activity.
In the first aspect of the present invention, there is provided compound or its pharmaceutically acceptable salt or molten shown in logical formula (I)
Agent compound：
Wherein, R and R1It is independently selected from by hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, virtue
Base, heteroaryl, aryl alkyl, heteroaryl alkyl, heterocyclic radical, cycloheteroalkylalkyl, alkoxy, cycloalkyloxy, aryloxy, alkyl
Sulfenyl, cycloalkylsulfanyl, artyl sulfo, alkoxy carbonyl, aryloxycarbonyl, acyl group, Thioacyl, acyloxy, acid amides
Base, urea groups, sulfinyl, alkyl sulphonyl, aryl sulfonyl, haloalkyl, carbamyl, cyano group, isocyano group, nitro, Asia
The group that nitro, thiocyanogen, isothiocyano, hydrazide group, sulfanyl, sulfo group and monosilane are formed, above-mentioned group is optionally by one
It is or multiple independently selected from by halogen, alkyl, alkoxy, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, aryl, heteroaryl, aryl
Alkyl, heteroaryl alkyl, heterocyclic radical, cycloheteroalkylalkyl, alkoxy, cycloalkyloxy, aryloxy, alkyl sulfenyl, cycloalkyl sulphur
Base, artyl sulfo, alkoxy carbonyl, aryloxycarbonyl, acyl group, Thioacyl, acyloxy, amide groups, urea groups, thionyl
It is base, alkyl sulphonyl, aryl sulfonyl, haloalkyl, carbamyl, cyano group, isocyano group, nitro, nitroso, thiocyanogen, different
Group substitution in the group that thiocyanogen, hydrazide group, sulfanyl, sulfo group and monosilane are formed；Or R and R1Together with they institute
The carbon-carbon double bond of connection is collectively forming 5-7 member unsaturated cyclic groups, and the unsaturated cyclic group is optionally containing 1-3 miscellaneous originals
Son, and be optionally independently selected by one or more from by halogen, alkyl, alkoxy, cycloalkyl, alkenyl, cycloalkenyl group, alkynes
Base, aryl, heteroaryl, aryl alkyl, heteroaryl alkyl, heterocyclic radical, cycloheteroalkylalkyl, alkoxy, cycloalkyloxy, aryl oxide
Base, alkyl sulfenyl, cycloalkylsulfanyl, artyl sulfo, alkoxy carbonyl, aryloxycarbonyl, acyl group, Thioacyl, acyl group oxygen
Base, amide groups, urea groups, sulfinyl, alkyl sulphonyl, aryl sulfonyl, haloalkyl, carbamyl, cyano group, isocyano group,
Group substitution in the group that nitro, nitroso, thiocyanogen, isothiocyano, hydrazide group, sulfanyl, sulfo group and monosilane are formed；
And
R2And R3Be independently selected from by hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, aryl, aryl alkyl,
Alkoxy, cycloalkyloxy, aryloxy, alkyl sulfenyl, cycloalkylsulfanyl, artyl sulfo, Thioacyl, hydrazide group and sulfanyl
The group formed, above-mentioned group are optionally independently selected by one or more from by halogen, hydroxyl, alkyl, hydroxy alkyl, alkene
Base, alkynyl, alkoxy, hydroxy alkoxy base, alkoxy carbonyl group, alkyl sulfenyl, aryl, hydroxyaryl, heteroaryl, heterocyclic radical, oxo
Heterocyclic radical, amide groups, alkyl sulphonyl, alkoxyphosphonyl groups, aryloxy, cycloalkylsulfanyl, artyl sulfo, Thioacyl,
Group substitution in the group that nitro, nitroso, hydrazide group, sulfanyl and monosilane are formed；Or R2And R3Together with they institute
The nitrogen-atoms of connection is collectively forming 5-7 circle heterocycles bases, above-mentioned heterocyclic radical be optionally independently selected by one or more from by hydroxyl,
Halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, hydroxy alkyl, aryl alkyl, heteroaryl alkyl, heterocyclic radical, heterocyclic radical
Alkyl, alkoxy, cycloalkyloxy, aryloxy, alkyl sulfenyl, cycloalkylsulfanyl, artyl sulfo, alkoxy carbonyl, aryl oxide
Base carbonyl, acyl group, Thioacyl, acyloxy, amide groups, urea groups, sulfinyl, alkyl sulphonyl, aryl sulfonyl, halo
Alkyl, carbamyl, cyano group, isocyano group, nitro, nitroso, thiocyanogen, isothiocyano, hydrazide group, sulfanyl, sulfo group and first
Group substitution in the group that silane is formed.
In a preferred embodiment, R and R1It is independently selected from by hydrogen, halogen, C1-C4Alkyl, C1-C4Alcoxyl
The group that base, phenyl and six membered heteroaryl are formed, above-mentioned C1-C4Alkyl, C1-C4Alkoxy, phenyl and six membered heteroaryl optionally quilt
One or more is independently selected from by halogen, C1-C4Alkyl and C1-C4Group substitution in the group that alkoxy is formed；Or
Person, R and R1The carbon-carbon double bond connected together with them is collectively forming 5-7 member cycloalkenyls, and the 5-7 member cycloalkenyls optionally contain 1
Individual hetero atom, and be optionally independently selected by one or more from by halogen, C1-C4Alkyl and C1-C4What alkoxy was formed
Group substitution in group.
In further preferred embodiment, R and R1It is independently selected from by hydrogen, chlorine, methyl, phenyl and pyridine
The group that base is formed, above-mentioned methyl, phenyl and pyridine radicals are optionally independently selected by one or more from by chlorine and methoxyl group institute
Group substitution in the group of composition；Or R and R1The carbon-carbon double bond connected together with them is collectively forming cyclohexenyl group.
In another preferred embodiment, R2And R3It is independently selected from by hydrogen, C1-C4Alkyl, C1-C4Alcoxyl
The group that base, 5-7 members cycloalkyl and phenyl are formed, above-mentioned C1-C4Alkyl, C1-C4Alkoxy, 5-7 members cycloalkyl and phenyl are by one
It is individual or multiple independently selected from by halogen, hydroxyl, C1-C4Alkyl, hydroxyl C1-C4Alkyl, C2-C4Alkenyl, C1-C4Alkoxy, hydroxyl
Base C1-C4Alkoxy, C1-C4Alkoxy carbonyl group, C1-C4Alkyl sulfenyl, phenyl, hydroxy phenyl, 5-7 unit's heteroaryls, 5-7 circle heterocycles
Base, 5-7 member oxo heterocycles base, C1-C4Amide groups, C1-C4Alkyl sulphonyl, C1-C4In the group that alkoxyphosphonyl groups are formed
Group substitutes；Or R2And R3The nitrogen-atoms connected together with them is collectively forming 5-6 circle heterocycles bases, above-mentioned heterocyclic radical optionally quilt
One or more is independently selected from by hydroxyl, hydroxyl C1-C4Alkyl and C1-C4Group in the group that alkyl sulphonyl is formed
Substitution.
In further preferred embodiment, R2And R3It is independently selected from by hydrogen, C1-C4Alkyl, cyclohexyl and
The group that phenyl is formed, above-mentioned C1-C4Alkyl, cyclohexyl and phenyl are independently selected by one or more from by chlorine, hydroxyl, first
Base, hydroxymethyl, pi-allyl, C1-C2Alkoxy, hydroxyl-oxethyl, carbethoxyl group, methyl mercapto, phenyl, hydroxy phenyl, pyridine
The group that base, furyl, tetrahydrofuran base, oxoimidazolidinyl, acetamido, mesyl, diethoxy phosphonium mesitoyl base are formed
In group substitution；Or R2And R3The nitrogen-atoms connected together with them is collectively forming nafoxidine base, piperidyl or piperazine
Base, above-mentioned nafoxidine base, piperidyl or piperazinyl be optionally independently selected by one or more from by hydroxyl, hydroxymethyl and
Group substitution in the group that mesyl is formed.
In most preferred embodiments, R2And R3It is independently selected from by hydrogen, benzyl, methoxy-propyl, hexamethylene
Base, normal-butyl, the tert-butyl group, hydroxypropyl, ethoxycarbonyl-ethyl, methylthio, pi-allyl, picolyl, furfuryl, hydroxyl
Base ethyl, hydroxybutyl, dihydroxypropyl, hydroxyethoxy ethyl, tetrahydrofuran ylmethyl, hydroxy-cyclohexyl, hydroxyphenylmethyl,
Phenyl (methylol) methyl, acetamido ethyl, oxoimidazolidinyl ethyl, methylsulfonylethyl, diethoxy propyl group, diethyl
The group that epoxide phosphonoethyl, aminomethyl phenyl and chloroethyl are formed；Or R2And R3The nitrogen-atoms connected together with them is total to
With formation hydroxy piperidine base, methylol nafoxidine base, mesylpiperazinyl.
In the second aspect of the present invention, there is provided a kind of pharmaceutical composition, described pharmaceutical composition include：The present invention first
The aspect compound or its pharmaceutically acceptable salt or solvate；And pharmaceutically acceptable carrier.
In the third aspect of the present invention, there is provided the method for preparing compound described in first aspect present invention, methods described
Including as follows by hydroquinones, raw material A and raw material B in the NaCl aqueous solution, NaI and organic nitrile (preferably CH3CN sent out in the presence of)
Raw reaction：
Wherein each substituent is as defined in logical formula (I).
In the fourth aspect of the present invention, there is provided compound described in first aspect present invention and its pharmaceutically acceptable
The purposes of salt or solvate in terms of preparing for anti-tumor drug.
In a preferred embodiment, the tumour is selected from by prostate cancer, lung cancer, breast cancer, liver cancer, stomach cancer, palace
The group that neck cancer, colon cancer and epithelioma are formed.
Embodiment
The term " alkyl " used in the present invention refers to degree of unsaturation is only made up of and do not had carbon atom and hydrogen atom
The group of (such as double bond, three keys or ring), it covers various possible geometrical isomerism groups and alloisomerism group.The group
It is connected by singly-bound with the remainder of molecule.As the non-limiting examples of alkyl, following straight or branched can be enumerated
Group：Methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, the tert-butyl group, n-pentyl and its it is other seven kinds it is different
Structure body, n-hexyl and its other 16 kinds of isomers, n-heptyl and its various isomers, n-octyl and its various isomers, just
Nonyl and its various isomers, positive decyl and its various isomers.
The term " cycloalkyl " used in the present invention refers to the non-aromatic ring system of saturation being made up of at least three carbon atom, should
Ring system can be monocyclic, bicyclic, polycyclic or condensed ring, bridged ring, loop coil., can be with as the non-limiting examples of cycloalkyl
Enumerate following group：Cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl, suberyl, cyclooctyl, cyclononyl, cyclodecyl；And by two
Individual or multiple above-mentioned monocyclic condensed ring, bridged ring or spiro-cyclic groups formed by common edge and public carbon atom.
The term " alkenyl " used in the present invention refers in abovementioned alkyl group one or more be present (in addition to methyl)
The group formed in the case of double bond.
The term " cycloalkenyl group " used in the present invention refers to one or more double bonds in above-mentioned group of naphthene base be present
In the case of the group that is formed.
The term " alkynyl " used in the present invention refers in abovementioned alkyl group one or more be present (in addition to methyl)
The group formed in the case of three key.
The term " alkoxy " used in the present invention refer to oxygen atom be connected with abovementioned alkyl and by the oxygen atom with
Singly-bound is connected to the group of molecule remainder, and it covers various possible geometrical isomerism groups and alloisomerism group.Make
For the non-limiting examples of alkoxy, the group of following straight or branched can be enumerated：It is methoxyl group, ethyoxyl, positive propoxy, different
Propoxyl group, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy and its other seven kinds of isomers, just own oxygen
Base and its other 16 kinds of isomers, positive epoxide in heptan and its various isomers, n-octyloxy and its various isomers, positive nonyl epoxide
And its various isomers, n-decyloxy and its various isomers.
The term " aryl " used in the present invention refers to the aromatic ring being made up of at least six carbon atom, and the ring system can be with
It is monocyclic, bicyclic, polycyclic, wherein bicyclic and polycyclic can be formed by monocyclic by way of singly-bound connected mode or fusion.As
The non-limiting examples of aryl, following group can be enumerated：Phenyl, naphthyl, anthryl, phenanthryl, indenyl, pyrenyl, base, azulenyl,
Pentalene base, heptalene base, acenaphthenyl, fluorenyl, that non-alkenyl, firefly anthryl, vinegar phenanthrene alkenyl, benzo acenaphthenyl, Sanya phenyl,Base,
Aphthacene base, Pi base, pentaphene base, pentacene base, four adjacent phenylenes, hexaphene base, hexacene base, cool base, three naphthylenes, heptaphene
Base, heptacene base, pyrrole anthryl, ovalene base, xenyl, binaphthyl.
The term " heteroaryl " used in the present invention refers to one or more hetero atoms independently selected from N, O or S
5-14 member heteroaromatic ring systems, the ring system can be it is monocyclic, bicyclic, polycyclic, wherein it is bicyclic and it is polycyclic can be by monocyclic logical
Cross singly-bound connected mode or fusion mode is formed.As the non-limiting examples of heteroaryl, following group can be enumerated：Oxazole
Base, isoxazolyls, imidazole radicals, furyl, indyl, isoindolyl, pyrrole radicals, triazolyl, triazine radical, tetrazole radical, thienyl,
Thiazolyl, isothiazolyl, pyridine radicals, pyrimidine radicals, pyrazinyl, pyridazinyl, benzofuranyl, benzothiazolyl, benzoxazolyl,
Benzimidazolyl, benzothienyl, benzopyranyl, carbazyl, quinolyl, isoquinolyl, quinazolyl, cinnolines base, naphthyridines
Base, pteridyl, purine radicals, quinoxalinyls, thiadiazolyl group, indolizine base, acridinyl, phenazinyl, phthalazinyl, cumarin base, pyrrole
Azoles and pyridine radicals, pyrido pyridazinyl, pyrrolopyridinyl, imidazopyridyl, pyrazolo pyridazine base；And by above-mentioned heteroaryl
The group that base is formed by way of singly-bound connected mode or fusion.
The term " heterocyclic radical " used in the present invention refers to what is be made up of carbon atom with the hetero atom for being independently selected from N, O or S
Non-aromatic 3-15 member ring systems, the ring system can be monocyclic, bicyclic or polycyclic or condensed ring, bridged ring, loop coil, and can
Optionally to include one or more double bonds.As the non-limiting examples of heterocyclic radical, following group can be enumerated：Azepine
Base, acridinyl, benzodioxole group, benzo dioxane hexyl, chromanyl, dioxolanyl, two
Oxygen phospha cyclopenta, Decahydroisoquinolinpreparation base, indanyl, indoline base, isoindoline base, isochroman base, isothiazole
Alkyl, isoxazole alkyls, morpholinyl, oxazolinyl, oxazolidine Ji, oxadiazolyls, 2- oxopiperazinyls, 2- oxo-piperidine bases,
2- oxo-pyrrolidines base, 2- oxo azepinesBase, octahydro indyl, octahydro isoindolyl, perhydroazepineBase, piperazinyl,
4- piperidone bases, piperidyl, phenothiazinyl, phenoxazine groups, quininuclidinyl, tetrahydro isoquinolyl, tetrahydrofuran base, oxinane
Base, nafoxidine base, thiazolinyl, thiazolidinyl, thio-morpholinyl, thiomorpholino sulfoxide and thio-morpholinyl sulfone.
The term " aryl alkyl " used in the present invention refers to the alkyl that one or more hydrogen atoms are independently substituted by aryl,
Wherein described aryl and alkyl are as hereinbefore defined.
The term " heteroaryl alkyl " used in the present invention refers to what one or more hydrogen atoms were independently substituted by heteroaryl
Alkyl, wherein described heteroaryl and alkyl are as hereinbefore defined.
The term " halogen " used in the present invention or " halo " refer to fluorine, chlorine, bromine or iodine.
Pharmaceutical composition in the present invention contains compound described in first aspect present invention as active component.In addition,
The pharmaceutical composition can also include pharmaceutically acceptable carrier, include but is not limited to：It is water, salting liquid, alcohol, polyethylene glycol, more
Castor oil, peanut oil, olive oil, gelatin, lactose, land plaster, sucrose, dextrin, magnesium carbonate, sugar, the ring paste of hydroxyl-oxethyl
Essence, amylose, magnesium stearate, talcum, gelatin, agar, pectin, Arabic gum, stearic acid or the low alkyl ether of cellulose, silicon
Acid, aliphatic acid, fatty acid amine, glycerine monofatty ester and two glyceride, the sour ether of pentaerythrite fat, polyoxyethylene, methylol
Cellulose and polyvinylpyrrolidone.The pharmaceutical composition can also include one or more pharmaceutically acceptable adjuvants, profit
Humectant, emulsifying agent, suspending agent, preservative, osmotic pressure regulator, buffer, sweetener, flavouring, colouring agent or above-mentioned times
Meaning combination.
Any type of preparation, such as capsule, tablet, aerosol, solution can be made in the pharmaceutical composition of the present invention
Agent, suspending agent, sugar-coat agent, lozenge, syrup, emulsion, ointment, paste, injection, powder, granule, paste, sustained release agent,
Foaming agent.According to method of administration, oral Preparation, nasal administration preparation, pulmonary administration system can be made in medicine of the invention
Agent, buccal preparation, transdermal formulations, intradermal administration preparation, percutaneous drug administration preparation, Parenteral formulations, rectum are given
Medicine preparation, reservoir type drug-delivery preparation, preparation for intravenous administration, drug-delivery preparation, intramuscular administration preparation, intranasal administration system in urethra
Agent, dosing eyes preparation, epidural administration preparation or local administration preparation.
" cancer " in the present invention includes various cancers as known in the art, includes but is not limited to：Lung cancer, liver cancer, stomach
Cancer, cervical carcinoma, colon cancer, breast cancer, leukaemia, non-small cell carcinoma, prostate cancer or tired melanoma, the cancer of the brain, cutaneum carcinoma, bone
Cancer, lymph cancer, nasopharyngeal carcinoma, laryngocarcinoma, cancer of the esophagus, duodenal cancer, carcinoma of small intestine, colorectal cancer, cancer of pancreas, kidney, genital cancer,
Thyroid cancer.
Embodiment
Next, the present invention is illustrated in further detail by embodiment, but the present invention is not limited only to these realities
Apply example.
Compound in the following embodiments of the present invention is synthesized by following universal method, wherein each substituent such as formula
(I) defined in.
Using hydroquinones 1mmol, the amine 3mmol as raw material A, pi-allyl isothiourea 1mmol and NaI as raw material B
0.5mmol is added to 20mL/5mL CH3In CN/NaCl (saturation) system, it is stirred at room temperature to TLC monitoring hydroquinones and has reacted
Entirely.Then saturated aqueous common salt 20mL, ethyl acetate extraction (15mL × 3), anhydrous sodium sulfate drying, ethyl acetate/oil are added
Ether column chromatography, revolving remove solvent, acetone/petroleum ether recrystallization.
In the examples below, all source chemicals are that commercially available chemistry is pure or AR, are directly made without processing
With.Other related experiment instrument conditions are as follows：
Column chromatography：Haiyang Chemical Plant, Qingdao's silica gel 200-300 mesh.
Melting point apparatus：X-4 type micro-meldometers.
Mass spectrograph：APEX IV type Fourier transform high resolution mass spectrums.
NMR：Bruker-400MHz
Colour developing：It is iodine, ultraviolet.
Embodiment 1：2- allyl sulfenyl -5- benzyl amino 1,4-benzoquinone
Red solid, yield 69%, m.p.109.0-109.9 DEG C
1H NMR(400MHz,CDCl3)δ7.41-7.30(m,5H),6.26(s,1H),6.19(s,1H),5.87(ddt,J
=16.7,10.1,6.4Hz, 1H), 5.55 (s, 1H), 5.40 (dd, J=17.0,1.0Hz, 1H), 5.29 (dd, J=10.1,
0.8Hz, 1H), 4.32 (d, J=5.8Hz, 2H), 3.46 (d, J=6.4Hz, 2H)；13C NMR(101MHz,CDCl3)δ181.3,
179.2,158.4,147.2,135.6,130.3,129.0,128.2,127.7,120.5,119.9,97.9,46.8,33.4；
HRMS(ESI):m/z calcd for C16H16NO2S[M+H]+:286.08963,found:286.08984.
Embodiment 2：2- allyl sulfenyls -5- (3- methoxyl groups) third amino 1,4-benzoquinone
Red solid, yield 65%, m.p.77.3-77.6 DEG C
1H NMR(400MHz,CDCl3) δ 6.38 (br, 1H), 6.23 (s, 1H), 5.87 (ddt, J=16.7,10.2,
6.5Hz, 1H), 5.49 (s, 1H), 5.39 (d, J=17.0Hz, 1H), 5.28 (d, J=10.1Hz, 1H), 3.50 (t, J=
5.6Hz, 2H), 3.46 (d, J=6.4Hz, 2H), 3.38 (s, 3H), 3.25 (dd, J=12.4,6.3Hz, 2H), 1.97-1.87
(m,2H)；13C NMR(101MHz,CDCl3)δ181.1,179.2,158.6,147.7,130.4,120.4,119.8,96.63,
70.7,58.9,40.8,33.4 28.0；HRMS(ESI):m/z calcd for C13H18NO3S[M+H]+:268.10019,
found:268.10042.
Embodiment 3：2- allyl sulfenyl -5- Cyclohexylamino 1,4-benzoquinone
Red solid, yield 73%, m.p.92.5-93.4 DEG C
1H NMR(400MHz,CDCl3) δ 6.23 (s, 1H), 5.87 (ddt, J=16.6,10.1,6.4Hz, 2H), 5.51
(s, 1H), 5.39 (dd, J=17.0,1.1Hz, 1H), 5.28 (dd, J=10.1,1.0Hz, 1H), 3.45 (d, J=6.4Hz,
2H), 3.33-3.16 (m, 1H), 2.08-1.88 (m, 2H), 1.90-1.72 (m, 2H), 1.66 (d, J=5.8Hz, 1H), 1.31
(ddd, J=24.4,14.5,2.9Hz, 5H)；13C NMR(101MHz,CDCl3)δ181.0,179.4,158.7,146.2,
130.4,120.3,119.81,96.8,51.3,33.4,31.8,25.4,24.5；HRMS(ESI):m/z calcd for
C15H20NO2S[M+H]+:278.12093,found:278.12107.
Embodiment 4：2- allyl sulfenyl -5- n-butyl amine base 1,4-benzoquinone
Red solid, yield 71%, m.p.83.5-84.2 DEG C
1H NMR(400MHz,CDCl3) δ 6.24 (s, 1H), 6.12-5.73 (m, 2H), 5.49 (s, 1H), 5.40 (dd, J=
17.0,1.0Hz, 1H), 5.29 (dd, J=10.1,1.0Hz, 1H), 3.46 (d, J=6.5Hz, 2H), 3.13 (dd, J=13.2,
6.9Hz, 2H), 1.70-1.60 (m, 2H), 1.49-1.36 (m, 2H), 0.97 (t, J=7.3Hz, 3H)；13C NMR(101MHz,
CDCl3)δ181.1,179.3,158.7,147.5,130.4,120.3,119.8,96.8,42.3,33.4,30.2,20.1,
13.6；HRMS(ESI):m/z calcd for C13H18NO2S[M+H]+:252.10528,found:252.10575.
Embodiment 5：The tertiary fourth amino 1,4-benzoquinone of 2- allyl sulfenyls -5-
Red solid, yield 50%, m.p.113.9-114.6 DEG C
1H NMR(400MHz,CDCl3)δ6.24(s,1H),5.96(br,1H),5.91-5.80(m,1H),5.71(s,
1H), 5.39 (dd, J=17.0,1.0Hz, 1H), 5.28 (dd, J=10.1,1.0Hz, 1H), 3.45 (d, J=6.4Hz, 2H),
1.40(s,9H)；13C NMR(101MHz,CDCl3)δ180.8,179.7,158.2,145.2,130.36,120.4,119.8,
98.8,51.9,33.3,28.3；HRMS(ESI):m/z calcd for C13H18NO2S[M+H]+:252.10528,found:
252.10574.
Embodiment 6：2- allyl sulfenyls -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 72%, m.p.100.6-101.4 DEG C
1H NMR(400MHz,CDCl3) δ 6.28 (s, 1H), 6.23 (s, 1H), 5.86 (ddt, J=16.7,10.1,
6.5Hz, 1H), 5.50 (s, 1H), 5.39 (d, J=17.0Hz, 1H), 5.28 (d, J=10.1Hz, 1H), 4.10 (s, 1H),
3.45 (d, J=6.4Hz, 2H), 3.20 (ddd, J=13.7,6.3,3.7Hz, 1H), 3.08 (ddd, J=13.6,7.8,
5.5Hz, 1H), 2.23 (d, J=37.2Hz, 1H), 1.30 (d, J=6.3Hz, 3H)；13C NMR(101MHz,CDCl3)δ
181.3,179.1,158.5,147.7,130.3,120.4,119.9,97.2,65.6,49.4,33.4,21.3；HRMS(ESI):
m/zcalcd for C12H16NO3S[M+H]+:254.08454,found:254.08478.
Embodiment 7：3- (4- (allyl sulfenyl) -5- (2- carbethoxyl groups) ethylamino 1,4-benzoquinone
Red solid, yield 61%, m.p.94.0-94.9 DEG C
1H NMR(400MHz,CDCl3) δ 6.25 (s, 1H), 6.17 (s, 1H), 5.87 (ddt, J=16.7,10.1,
6.5Hz, 1H), 5.52 (s, 1H), 5.39 (dd, J=17.0,0.9Hz, 1H), 5.29 (d, J=10.1Hz, 1H), 3.74 (s,
3H), 3.46 (q, J=6.3Hz, 4H), 2.66 (t, J=6.4Hz, 2H)；13C NMR(101MHz,CDCl3)δ181.3,179.0,
171.5,158.3,147.1,130.3,120.5,119.9,97.2,52.1,37.9,33.4,32.4；HRMS(ESI):m/z
calcd for C13H16NO4S[M+H]+:282.07946,found:282.07982.
Embodiment 8：2- allyl sulfenyls -5- (3- methyl mercaptos) third amino 1,4-benzoquinone
Red solid, yield 62%, m.p.66.7-67.5 DEG C
1H NMR(400MHz,CDCl3) δ 6.24 (s, 1H), 6.00 (s, 1H), 5.87 (ddt, J=16.7,10.1,
6.5Hz, 1H), 5.53 (s, 1H), 5.39 (dd, J=17.0,1.0Hz, 1H), 5.29 (dd, J=10.1,0.9Hz, 1H), 3.46
(d, J=6.5Hz, 2H), 3.29 (q, J=6.6Hz, 2H), 2.58 (t, J=6.9Hz, 2H), 2.12 (s, 3H), 1.95 (p, J=
6.9Hz,2H)；13C NMR(101MHz,CDCl3)δ181.1,179.2,158.6,147.4,130.3,120.4,119.9,
97.1,41.3,33.4,31.5,27.1,15.6；HRMS(ESI):m/z calcd for C13H18NO2S2[M+H]+:
284.07735,found:284.07760.
Embodiment 9：2- allyl sulfenyl -5- allylamino 1,4-benzoquinone
Red solid, yield 60%, m.p.108.5-109.4 DEG C
1H NMR(400MHz,CDCl3)δ6.26(s,1H),5.99(s,1H),5.94-5.78(m,2H),5.51(s,1H),
5.40 (d, J=17.0Hz, 1H), 5.34-5.24 (m, 3H), 3.79 (t, J=5.7Hz, 2H), 3.46 (d, J=6.4Hz, 2H)
；13C NMR(101MHz,CDCl3)δ181.3,179.2,158.4,147.2,131.3,130.3,120.4,119.9,118.4,
97.71,44.9,33.4；HRMS(ESI):m/z calcd for C12H14NO2S[M+H]+:236.07398,found:
236.07443.
Embodiment 10：2- allyl sulfenyls -5- (3- picolyls) amino 1,4-benzoquinone
Red solid, yield 73%, m.p.117.2-118.0 DEG C
1H NMR(400MHz,CDCl3) δ 8.71-8.56 (m, 2H), 7.62 (d, J=7.8Hz, 1H), 7.33 (dd, J=
7.8,4.9Hz, 1H), 6.28 (s, 1H), 6.18 (s, 1H), 5.87 (ddt, J=16.7,10.1,6.4Hz, 1H), 5.54 (s,
1H), 5.40 (d, J=17.0Hz, 1H), 5.30 (d, J=10.1Hz, 1H), 4.37 (d, J=5.9Hz, 2H), 3.47 (d, J=
6.4Hz,2H)；13C NMR(101MHz,CDCl3)δ181.4,179.0,158.2,149.7,149.11,147.0,135.2,
131.3,130.2,123.8,120.6,112.0,98.4,44.2,33.4；HRMS(ESI):m/z calcd for
C15H15N2O2S[M+H]+:287.08487,found:287.08508.
Embodiment 11：2- allyl sulfenyls -5- (2- furfuryls) amino 1,4-benzoquinone
Red solid, yield 61%, m.p.124.4-124.8 DEG C
1H NMR(400MHz,CDCl3) δ 7.41 (s, 1H), 6.37 (d, J=2.6Hz, 1H), 6.32 (d, J=3.1Hz,
1H), 6.26 (s, 1H), 6.12 (s, 1H), 5.87 (ddt, J=16.5,9.9,6.4Hz, 1H), 5.63 (s, 1H), 5.40 (d, J
=17.0Hz, 1H), 5.29 (d, J=10.1Hz, 1H), 4.31 (d, J=5.8Hz, 2H), 3.46 (d, J=6.4Hz, 2H)；13C
NMR(101MHz,CDCl3)δ181.4,179.1,158.2,148.7,146.9,142.9,130.3,120.5,119.9,
110.6,108.8,97.9,39.6,33.4；HRMS(ESI):m/z calcd for C14H14NO3S[M+H]+:276.06889,
found:276.06957.
Embodiment 12：2- allyl sulfenyls -5- (4- hydroxyls) piperidyl 1,4-benzoquinone
Red solid, yield 75%, m.p.84.4-85.2 DEG C
1H NMR(400MHz,CDCl3) δ 6.19 (s, 1H), 5.93-5.83 (m, 1H), 5.80 (s, 1H), 5.39 (d, J=
16.9Hz, 1H), 5.28 (d, J=10.1Hz, 1H), 4.13-3.92 (m, 1H), 3.92-3.75 (m, 2H), 3.43 (d, J=
14.9Hz, 2H), 3.32 (ddd, J=35.5,19.4,15.1Hz, 2H), 2.07-1.94 (m, 2H), 1.72-1.65 (m, 3H)；13C NMR(101MHz,CDCl3)δ181.9,181.2,154.2,152.3,130.5,123.5,119.7,106.6,66.5,
46.3,33.9,33.2；HRMS(ESI):m/z calcd for C14H18NO3S[M+H]+:280.10019,found:
280.10053.
Embodiment 13：2- (2- methyl) allyl sulfenyls -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 70%, m.p.92.3-93.0 DEG C
1H NMR(400MHz,CDCl3)δ6.27(s,1H),6.23(s,1H),5.51(s,1H),5.10(s,1H),5.03
(s,1H),4.10(m,1H),3.42(s,2H),3.26-3.14(m,1H),3.13-3.00(m,1H),2.09(br,1H),1.30
(d, J=6.2Hz, 3H)；13C NMR(101MHz,CDCl3)δ181.3,179.1,159.0,147.7,137.9,120.5,
115.6,97.2,65.6,49.4,38.0,21.8,21.3；HRMS(ESI):m/z calcd for C13H18NO3S[M+H]+:
268.10019,found:268.10010.
Embodiment 14：2- (but-2-ene -1- bases) sulfenyl -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 71%, m.p.89.1-90.0 DEG C
1H NMR(400MHz,CDCl3) δ 6.26-6.23 (m, 1H), 5.82 (td, J=13.0,6.3Hz, 1H), 5.59-
5.43 (m, 1H), 4.10 (m, 1H), 3.40 (d, J=6.6Hz, 2H), 3.20 (ddd, J=13.5,6.1,3.7Hz, 1H),
3.13-3.01 (m, 1H), 2.08 (br, 1H), 1.73 (d, J=6.4Hz, 3H), 1.30 (d, J=6.3Hz, 3H)；13C NMR
(101MHz,CDCl3)δ181.3,179.1,158.9,147.7,131.4,122.8,120.2,97.2,65.6,49.4,32.9,
21.3,17.8；HRMS(ESI):m/z calcd for C13H18NO3S[M+H]+:268.10019,found:268.09984.
Embodiment 15：2- (cyclohexene -2- bases) sulfenyl -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 65%, m.p.119.9-120.5 DEG C
1H NMR(400MHz,CDCl3)δ6.32(s,1H),6.26(br,1H),6.03-5.92(m,1H),5.77-5.66
(m, 1H), 5.51 (s, 1H), 4.11 (br, 1H), 3.79 (s, 1H), 3.20 (ddd, J=13.7,6.4,3.7Hz, 1H), 3.08
(ddd, J=13.6,7.8,5.5Hz, 1H), 2.14-2.06 (m, 2H), 2.06-1.99 (m, 2H), 1.95-1.84 (m, 2H),
1.75-1.70 (m, 8.5Hz, 1H), 1.30 (d, J=6.3Hz, 3H)；13C NMR(101MHz,CDCl3)δ181.5,179.2,
158.5,147.6,132.5,124.2,120.0,97.4,65.7,49.4,39.8,27.6,24.7,21.3,19.7；HRMS
(ESI):m/z calcd for C15H20NO3S[M+H]+:294.11584,found:294.11571.
Embodiment 16：2- (2- chlorine) allyl sulfenyls -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 68%, m.p.93.6-94.3 DEG C
1H NMR(400MHz,CDCl3)δ6.29(br,1H),6.21(s,1H),5.58(s,1H),5.52(s,1H),5.45
(s,1H),4.11(br,1H),3.68(s,2H),3.26-3.16(m,1H),3.13-3.02(m,1H),2.08(s,1H),1.30
(dd, J=6.2,1.2Hz, 3H)；13C NMR(101MHz,CDCl3)δ181.0,179.1,157.3,147.6,134.6,
120.7,115.8,97.2,65.6,49.4,37.8,21.3；HRMS(ESI):m/z calcd for C12H15ClNO3S[M+H
]+:288.04557,found:288.04519.
Embodiment 17：2- (2- phenyl) allyl sulfenyls -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 58%, m.p.88.2-88.9 DEG C
1H NMR(400MHz,CDCl3)δ7.46-7.33(m,5H),6.28(s,1H),6.26(br,1H),5.60(s,
1H),5.51(s,1H),5.48(s,1H),4.10(br,1H),3.86(s,2H),3.23-3.17(m,1H),3.11-2.94(m,
1H), 1.83 (s, 1H), 1.30 (d, J=6.3Hz, 1H)；13C NMR(101MHz,CDCl3)δ181.2,179.1,159.0,
147.8,140.6,138.9,128.6,128.3,126.1,120.3,117.0,97.1,65.6,49.4,35.7,21.3；HRMS
(ESI):m/z calcd for C18H20NO3S[M+H]+:330.11584,found:330.11537.
Embodiment 18：2- (3- phenyl) allyl sulfenyls -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 51%, m.p.159.7-160.4 DEG C
1H NMR(400MHz,CDCl3) δ 7.43-7.28 (m, 5H), 6.71 (d, J=15.8Hz, 1H), 6.31 (s, 1H),
6.22 (dt, J=15.7,6.8Hz, 2H), 5.52 (s, 1H), 4.10 (br, 1H), 3.63 (d, J=6.8Hz, 2H), 3.21
(ddd, J=13.7,6.3,3.6Hz, 1H), 3.07 (ddd, J=13.6,7.8,5.4Hz, 1H), 1.88 (d, J=4.2Hz,
1H), 1.30 (d, J=6.3Hz, 3H)；13C NMR(101MHz,CDCl3)δ181.3,179.1,158.5,147.7,136.1,
134.8,128.7,128.1,126.5,121.4,120.4,97.3,65.7,49.3,33.1,21.3；HRMS(ESI):m/
zcalcd for C18H20NO3S[M+H]+:330.11584,found:330.11541.
Embodiment 19：2- (3- (2- methoxyl groups) phenyl) third amino 1,4-benzoquinone of allyl sulfenyl -5- (2- hydroxyls)
Red solid, yield 49%, m.p.87.9-88.8 DEG C
1H NMR(400MHz,CDCl3) δ 7.40 (dd, J=7.6,1.3Hz, 1H), 7.28-7.21 (m, 1H), 7.05-
6.85(m,3H),6.33(s,1H),6.28-6.19(m,2H),5.51(s,1H),4.21-4.03(m,1H),3.86(s,3H),
3.23-3.17 (m, 1H), 3.11-3.04 (m, 1H), 2.12 (br, 1H), 1.29 (d, J=6.3Hz, 3H)；13C NMR
(101MHz,CDCl3)δ181.4,179.0,158.7,156.8,147.7,130.1,129.1,127.1,125.2,122.0,
120.7,120.4,110.9,97.2,65.6,55.5,49.4,33.8,21.3；HRMS(ESI):m/z calcd for
C19H22NO4S[M+H]+:360.12641,found:360.12647.
Embodiment 20：2- (3- (4- fluorine) phenyl) third amino 1,4-benzoquinone of allyl sulfenyl -5- (2- hydroxyls)
Red solid, yield 49%, m.p.133.1-134.2 DEG C
1H NMR(400MHz,CDCl3) δ 7.34 (dd, J=8.4,5.5Hz, 2H), 7.02 (t, J=8.6Hz, 2H), 6.66
(d, J=15.7Hz, 1H), 6.28 (s, 2H), 6.20-6.03 (m, 1H), 5.51 (s, 1H), 4.11 (br, 1H), 3.62 (t, J=
10.8Hz, 2H), 3.20 (ddd, J=13.6,6.2,3.7Hz, 1H), 3.07 (ddd, J=13.6,7.7,5.6Hz, 1H), 2.16
(br, 1H), 1.30 (d, J=6.3Hz, 3H)；13C NMR(101MHz,CDCl3)δ181.2,179.1,158.5,147.7,
133.6,132.2,128.1,128.0,121.2,120.4,115.7,115.5,97.2,65.6,49.4,33.0,21.3；HRMS
(ESI):m/z calcd for C18H19FNO3S[M+H]+:348.10642,found:348.10575.
Embodiment 21：2- (3- (pyridin-3-yl)) allyl sulfenyl -5- (2- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 42%, m.p.155.0-155.7 DEG C
1H NMR (400MHz, DMSO) δ 8.63 (s, 1H), 8.45 (d, J=3.9Hz, 1H), 7.92 (d, J=7.7Hz,
1H), 7.35 (dd, J=11.7,6.7Hz, 2H), 6.77 (d, J=15.9Hz, 1H), 6.58-6.38 (m, 2H), 5.50 (s,
1H), 4.91 (s, 1H), 3.83-3.78 (m, 3H), 3.19-2.92 (m, 2H), 1.06 (d, J=6.0Hz, 3H)；13C NMR
(101MHz,DMSO)δ180.4,179.6,157.7,149.2,148.7,148.4,133.4,132.3,130.6,125.9,
124.2,121.2,96.2,64.5,50.00,32.3,21.6；HRMS(ESI):m/z calcd for C17H19FN2O3S[M+H
]+:331.11109,found:331.11042.
Embodiment 22：2- allyl sulfenyls -5- (2- hydroxyls) ethylamino 1,4-benzoquinone
Red solid, yield 52%, m.p.132.9-133.8 DEG C
1H NMR (400MHz, DMSO) δ 7.38 (t, J=5.7Hz, 1H), 6.35 (s, 1H), 5.86 (ddt, J=16.7,
10.1,6.6Hz, 1H), 5.47 (s, 1H), 5.37 (dd, J=17.0,1.3Hz, 1H), 5.23 (d, J=10.1Hz, 1H), 4.83
(br, 1H), 3.59 (d, J=6.5Hz, 2H), 3.55 (t, J=5.8Hz, 2H), 3.17 (q, J=5.9Hz, 2H)；13C NMR
(101MHz,DMSO)δ180.4,179.6,157.7,148.8,132.0,121.2,119.7,96.1,58.8,45.1,32.6；
HRMS(ESI):m/z calcd for C11H14NO3S[M+H]+:240.06889,found:240.06874.
Embodiment 23：2- allyl sulfenyls -5- (3- hydroxyls) third amino 1,4-benzoquinone
Red solid, yield 63%, m.p.111.0-111.9 DEG C
1H NMR(400MHz,CDCl3) δ 6.36 (br, 1H), 6.23 (s, 1H), 5.87 (ddt, J=16.7,10.1,
6.5Hz, 1H), 5.51 (s, 1H), 5.39 (d, J=16.9Hz, 1H), 5.28 (d, J=10.1Hz, 1H), 3.82 (t, J=
5.0Hz, 2H), 3.46 (d, J=6.4Hz, 2H), 3.30 (dd, J=12.5,6.3Hz, 2H), 1.95-1.89 (m, 3H)；13C
NMR(101MHz,CDCl3)δ181.1,179.2,158.7,147.7,130.3,120.4,119.9,96.7,60.7,40.4,
33.4,30.3；HRMS(ESI):m/z calcd for C12H16NO3S[M+H]+:254.08454,found:254.08432.
Embodiment 24：2- allyl sulfenyls -5- (4- hydroxyls) fourth amino 1,4-benzoquinone
Red solid, yield 71%, m.p.82.8-83.3 DEG C
1H NMR(400MHz,CDCl3) δ 6.23 (s, 1H), 6.07 (br, 1H), 5.87 (ddt, J=16.7,10.1,
6.5Hz, 1H), 5.49 (s, 1H), 5.39 (d, J=17.0Hz, 1H), 5.29 (d, J=10.1Hz, 1H), 3.72 (dd, J=
9.9,5.7Hz, 2H), 3.46 (d, J=6.4Hz, 2H), 3.19 (q, J=6.6Hz, 2H), 1.84-1.74 (m, 2H), 1.71-
1.65(m,2H),1.59(br,1H)；13C NMR(101MHz,CDCl3)δ181.1,179.2,158.7,147.5,130.3,
120.3,119.8,96.9,62.1,42.4,33.4,29.8,24.7；HRMS(ESI):m/z calcd for C13H18NO3S[M+
H]+:268.10019,found:268.09984.
Embodiment 25：2- allyl sulfenyls -5- (2,3- dihydroxy) third amino 1,4-benzoquinone
Red solid, yield 51%, m.p.109.4-110.4 DEG C
1H NMR (400MHz, DMSO) δ 7.32 (t, J=5.8Hz, 1H), 6.36 (s, 1H), 5.86 (ddt, J=16.7,
10.1,6.5Hz, 1H), 5.47 (s, 1H), 5.38 (d, J=17.0Hz, 1H), 5.23 (d, J=10.1Hz, 1H), 5.00 (d, J
=5.0Hz, 1H), 4.72 (t, J=5.6Hz, 1H), 3.68 (dd, J=10.7,5.4Hz, 1H), 3.59 (d, J=6.5Hz,
2H),3.40-3.35(m,1H),3.33-3.27(m,1H),3.26-3.19(m,1H),3.09-2.99(m,1H)；13C NMR
(101MHz,DMSO)δ180.3,179.5,157.8,148.7,132.0,121.2,119.7,96.1,69.4,64.2,46.1,
32.6；HRMS(ESI):m/z calcd for C12H16NO4S[M+H]+:270.07946,found:270.07887.
Embodiment 26：2- allyl sulfenyls -5- (2- (2- hydroxyls) ethyoxyl) ethylamino 1,4-benzoquinone
Red solid, yield 55%, m.p.65.9-66.3 DEG C
1H NMR(400MHz,CDCl3) δ 6.25 (s, 1H), 6.21 (s, 1H), 5.87 (ddt, J=16.7,10.1,
6.5Hz, 1H), 5.51 (s, 1H), 5.40 (d, J=7.0Hz, 1H), 5.29 (d, J=10.1Hz, 1H), 3.79 (br, 2H),
3.74 (t, J=5.2Hz, 2H), 3.66-3.60 (m, 2H), 3.47 (d, J=6.4Hz, 2H), 3.34 (dd, J=10.6,
5.3Hz,2H),2.00(br,1H)；13C NMR(101MHz,CDCl3)δ181.3,179.1,158.4,147.5,130.3,
120.5,119.9,97.2,72.4,68.1,61.8,42.3,33.4；HRMS(ESI):m/z calcd for C13H18NO4S[M+
H]+:284.09511,found:284.09483.
Embodiment 27：2- allyl sulfenyls -5- ((2- methylols) nafoxidine -1- bases) 1,4-benzoquinone
Red solid, yield 81%, m.p.83.2-84.1 DEG C
1H NMR(400MHz,CDCl3) δ 6.14 (s, 1H), 5.87 (ddt, J=16.7,10.1,6.5Hz, 1H), 5.61
(s, 1H), 5.39 (dd, J=17.0,0.9Hz, 1H), 5.28 (d, J=10.1Hz, 1H), 4.63 (br, 1H), 3.73-3.53
(m,3H),3.44-3.45(m,3H),2.29(br,1H),2.23-1.92(m,4H)；13C NMR(151MHz,CDCl3)δ
181.5,180.6,155.8,148.1,130.5,122.2,119.7,102.4,63.6,61.8,51.1,33.2,28.3,
22.0；HRMS(ESI):m/z calcd for C14H18NO3S[M+H]+:280.10019,found:280.09972.
Embodiment 28：2- allyl sulfenyls -5- (tetrahydrofuran -2- bases) methylamino 1,4-benzoquinone
Red solid, yield 60%, m.p.124.0-124.9 DEG C
1H NMR(400MHz,CDCl3) δ 6.24 (s, 1H), 6.17 (br, 1H), 5.87 (ddt, J=16.7,10.1,
6.4Hz, 1H), 5.51 (s, 1H), 5.39 (dd, J=17.0,0.9Hz, 1H), 5.28 (dd, J=10.1,0.9Hz, 1H), 4.12
(qd, J=7.1,3.7Hz, 1H), 3.96-3.88 (m, 1H), 3.85-3.76 (m, 1H), 3.46 (d, J=6.4Hz, 2H), 3.26
(ddd, J=13.7,6.0,3.7Hz, 1H), 3.16-3.05 (m, 1H), 2.06 (dt, J=12.3,6.7Hz, 1H), 2.00-
1.91 (m, 2H), 1.59 (ddd, J=15.1,12.1,7.5Hz, 1H)；13C NMR(101MHz,CDCl3)δ181.3,179.1,
158.3,147.6,130.3,120.4,119.8,97.1,76.2,68.3,46.3,33.4,29.1,25.7；HRMS(ESI):m/
z calcd for C14H18NO3S[M+H]+:280.10019,found:280.09990.
Embodiment 29：2- allyl sulfenyls -5- (trans -4- hydroxyls) Cyclohexylamino 1,4-benzoquinone
Red solid, yield 58%, m.p.142.8-143.5 DEG C
1H NMR(400MHz,CDCl3) δ 6.22 (s, 1H), 5.93-5.74 (m, 2H), 5.50 (s, 1H), 5.38 (d, J=
17.0Hz, 1H), 5.27 (d, J=10.1Hz, 1H), 3.68 (dd, J=11.5,7.9Hz, 1H), 3.45 (d, J=6.4Hz,
2H), 3.20 (dd, J=10.9,7.3Hz, 1H), 2.07 (t, J=14.2Hz, 4H), 1.91 (br, 1H), 1.39 (dt, J=
22.3,11.5Hz,4H)；13C NMR(101MHz,CDCl3)δ181.1,179.2,158.6,146.4,130.3,120.3,
119.9,97.1,69.3,50.6,33.4,29.5；HRMS(ESI):m/z calcd for C15H20NO3S[M+H]+:
294.11584,found:294.11576.
Embodiment 30：2- allyl sulfenyls -5- (2- hydroxyls) Cyclohexylamino 1,4-benzoquinone
Red solid, yield 63%, m.p.109.3-110.2 DEG C
1H NMR(400MHz,CDCl3) δ 6.25 (s, 1H), 6.02-5.78 (m, 2H), 5.65 (s, 1H), 5.40 (d, J=
17.3Hz, 1H), 5.29 (d, J=9.9Hz, 1H), 3.55 (br, 1H), 3.46 (d, J=6.3Hz, 2H), 3.14 (br, 1H),
2.08 (br, 2H), 1.91 (d, J=2.8Hz, 1H), 1.81-1.78 (m, 2H), 1.45-1.20 (m, 4H)；13C NMR
(101MHz,CDCl3)δ181.3,179.3,158.6,147.4,130.3,120.3,119.9,97.4,73.6,58.4,34.1,
33.4,30.3,24.3,24.0；HRMS(ESI):m/z calcd for C15H20NO3S[M+H]+:294.11584,found:
294.11577.
Embodiment 31：2- allyl sulfenyls -5- (4- hydroxyls) aminotoluene base 1,4-benzoquinone
Red solid, yield 63%, m.p.126.8-127.5 DEG C
1H NMR(400MHz,CDCl3) δ 7.16 (d, J=8.4Hz, 2H), 6.84 (d, J=8.5Hz, 2H), 6.26 (s,
1H), 6.13 (br, 1H), 5.87 (ddt, J=16.6,10.1,6.5Hz, 1H), 5.57 (s, 1H), 5.40 (d, J=17.1Hz,
2H), 5.29 (d, J=10.1Hz, 1H), 4.23 (d, J=5.7Hz, 2H), 3.47 (d, J=6.4Hz, 2H), 1.64 (s, 1H)；13C NMR(101MHz,CDCl3)δ181.4,179.2,158.6,155.7,147.2,130.3,129.3,127.5,120.4,
119.9,115.9,97.6,46.3,33.4；HRMS(ESI):m/z calcd for C16H16NO3S[M+H]+:302.08454,
found:302.08429.
Embodiment 32：2- allyl sulfenyls -5- (2- hydroxyls) aminotoluene base 1,4-benzoquinone
Red solid, yield 50%, m.p.149.6-150.2 DEG C
1H NMR (400MHz, DMSO) δ 9.74 (s, 1H), 7.93 (t, J=5.9Hz, 1H), 7.09 (t, J=7.9Hz,
2H), 6.83 (d, J=7.8Hz, 1H), 6.76 (t, J=7.4Hz, 1H), 6.35 (s, 1H), 5.84 (tt, J=10.0,6.6Hz,
1H), 5.38-5.34 (m, 2H), 5.22 (d, J=10.0Hz, 1H), 4.28 (d, J=6.3Hz, 2H), 3.57 (d, J=6.4Hz,
2H)；13C NMR(101MHz,DMSO)δ180.4,179.6,157.6,155.2,148.4,132.0,128.8,128.8,
123.1,121.4,119.7,119.5,115.6,96.5,40.8,32.6；HRMS(ESI):m/z calcd for C16H16NO3S
[M+H]+:302.08454,found:302.08408.
Embodiment 33：2- allyl sulfenyls -5- (2- hydroxyl -1- phenyl) ethylamino 1,4-benzoquinone
Red solid, yield 51%, m.p.116.4-117.3 DEG C
1H NMR(400MHz,CDCl3) δ 7.41-7.24 (m, 5H), 6.68 (d, J=5.6Hz, 1H), 6.25 (s, 1H),
5.85 (ddt, J=12.8,10.1,6.4Hz, 1H), 5.39 (d, J=17.0Hz, 1H), 5.29-5.27 (m, 2H), 4.45 (dd,
J=10.3,5.8Hz, 1H), 4.10-3.94 (m, 1H), 3.93-3.80 (m, 1H), 3.44 (d, J=6.3Hz, 1H), 2.09
(br,1H)；13C NMR(101MHz,CDCl3)δ181.4,179.3,158.1,146.8,136.9,130.3,129.2,128.4,
126.6,120.6,119.9,99.4,66.1,58.7,33.4；HRMS(ESI):m/z calcd for C17H18NO3S[M+H]+:
316.10019,found:316.09965.
Embodiment 34：2- allyl sulfenyls -5- (2- acetylaminos) ethylamino 1,4-benzoquinone
Red solid, yield 45%, m.p.138.2-139.0 DEG C
1H NMR(400MHz,DMSO)δ8.01(br,1H),7.58(br,1H),6.34(s,1H),5.97-5.77(m,
1H), 5.49 (s, 1H), 5.37 (d, J=17.0Hz, 1H), 5.23 (d, J=10.1Hz, 1H), 3.59 (d, J=6.4Hz, 2H),
3.25-3.10(m,4H),1.79(s,3H)；13C NMR(101MHz,DMSO)δ180.5,179.5,170.3,157.5,148.8,
132.0,121.3,119.7,96.0,42.5,37.3,32.6,23.0；HRMS(ESI):m/z calcd for C13H17N2O3S
[M+H]+:281.09544,found:281.09495.
Embodiment 35：2- allyl sulfenyls -5- (2- imidazolone -1- bases) ethylamino 1,4-benzoquinone
Red solid, yield 58%, m.p.134.3-135.1 DEG C
1H NMR(400MHz,CDCl3) δ 6.70 (br, 1H), 6.22 (s, 1H), 5.86 (ddt, J=16.7,10.2,
6.5Hz, 1H), 5.48 (s, 1H), 5.38 (d, J=17.0Hz, 1H), 5.27 (d, J=10.1Hz, 1H), 5.09 (s, 1H),
3.55-3.47 (m, 6H), 3.45 (d, J=6.5Hz, 2H), 3.27 (dd, J=11.0,5.4Hz, 2H)；13C NMR(101MHz,
CDCl3)δ181.3,178.9,163.4,158.1,147.9,130.3,120.6,119.8,96.9,45.9,42.3,41.7,
38.4,33.4；HRMS(ESI):m/z calcd for C14H18N3O3S[M+H]+:308.10634,found:308.10587.
Embodiment 36：2- allyl sulfenyls -5- (1- mesyls) piperazine -4- base 1,4-benzoquinone
Red solid, yield 61%, m.p.137.9-138.8 DEG C
1H NMR(400MHz,CDCl3) δ 6.22 (s, 1H), 5.92-5.83 (m, 1H), 5.81 (s, 1H), 5.39 (dd, J=
17.0,0.8Hz, 1H), 5.29 (d, J=10.1Hz, 1H), 3.61-3.54 (m, 4H), 3.46 (d, J=6.4Hz, 2H), 3.43-
3.35(m,4H),2.84(s,3H)；13C NMR(101MHz,CDCl3)δ182.3,180.7,153.9,151.9,130.3,
123.8,119.9,109.1,48.4,45.3,34.8,33.2；HRMS(ESI):m/z calcd for C14H19N2O4S2[M+H
]+:343.07807,found:349.07726
Embodiment 37：2- allyl sulfenyls -5- (2- mesyls) ethylamino 1,4-benzoquinone
Red solid, yield 55%, m.p.135.5-136.4 DEG C
1H NMR(400MHz,DMSO)δ7.59(br,1H),6.38(s,1H),6.04-5.76(m,1H),5.55(s,
1H), 5.38 (d, J=17.0Hz, 1H), 5.23 (d, J=9.9Hz, 1H), 3.60-3.55 (m, 4H), 3.42 (d, J=5.7Hz,
2H)；13C NMR(101MHz,DMSO)δ180.8,179.4,157.3,148.0,132.0,121.5,119.8,97.0,51.7,
41.1,36.3,32.6；HRMS(ESI):m/z calcd for C12H16NO4S2[M+H]+:302.05153,found:
302.05116.
Embodiment 38：2- allyl sulfenyls -5- (3,3- diethoxies) third amino 1,4-benzoquinone
Red solid, yield 55%, m.p.104.1-104.8 DEG C
1H NMR(400MHz,CDCl3) δ 6.61 (br, 1H), 6.23 (s, 1H), 5.87 (td, J=16.7,6.6Hz, 1H),
5.47 (s, 1H), 5.39 (d, J=17.0Hz, 1H), 5.28 (d, J=10.2Hz, 1H), 4.62 (t, J=4.7Hz, 1H),
3.79-3.66 (m, 2H), 3.59-3.49 (m, 2H), 3.45 (d, J=6.2Hz, 2H), 3.24 (dd, J=11.6,5.6Hz,
2H), 1.99 (dd, J=11.3,5.4Hz, 2H), 1.27 (t, J=7.0Hz, 6H)；13C NMR(101MHz,CDCl3)δ181.1,
179.2,158.6,147.6,130.4,120.4,119.8,102.0,96.5,62.3,38.5,33.4,31.8,15.3；HRMS
(ESI):m/z calcd for C16H24NO4S[M+H]+:326.14206,found:326.14190.
Embodiment 39：1- (4- allyl sulfenyl -3,6- dioxo -1,4- cyclohexadienyls) amino-ethyl diethyl phosphate
Red liquid, yield 31%
1H NMR(400MHz,CDCl3) δ 6.33 (br, 1H), 6.24 (s, 1H), 5.86 (ddt, J=16.7,10.1,
6.5Hz, 1H), 5.49 (s, 1H), 5.39 (dd, J=17.0,1.0Hz, 1H), 5.28 (dd, J=10.1,0.9Hz, 1H),
4.26-4.07 (m, 4H), 3.49-3.37 (m, 4H), 2.13-2.05 (m, 2H), 1.36 (t, J=7.1Hz, 6H)；13C NMR
(101MHz,CDCl3)δ181.3,178.9,158.2,147.0,130.3,120.5,119.9,97.3,62.2,62.1,36.7,
36.7,33.4,25.4,24.0,16.5,16.4；HRMS(ESI):m/z calcd for C15H23NO5PS[M+H]+:
360.10291,found:360.10299.
Embodiment 40：2- allyl sulfenyl -5- p-totuidine base 1,4-benzoquinone
Red solid, yield 46%, m.p.143.1-143.8 DEG C
1H NMR(400MHz,CDCl3) δ 7.49 (br, 1H), 7.21 (d, J=8.0Hz, 2H), 7.12 (d, J=8.1Hz,
2H), 6.34 (s, 1H), 6.12 (s, 1H), 5.89 (ddt, J=12.8,10.1,6.4Hz, 1H), 5.42 (d, J=17.0Hz,
1H), 5.31 (d, J=10.0Hz, 1H), 3.49 (d, J=6.2Hz, 2H), 2.37 (s, 3H)；13C NMR(101MHz,CDCl3)δ
182.2,179.5,158.0,144.2,135.8,134.5,130.3,130.2,122.4,120.5,119.9,99.4,33.4,
21.0；HRMS(ESI):m/z calcd for C16H16NO2S[M+H]+:286.08963,found:286.08953.
Embodiment 41：2- allyl sulfenyls -5- (2- chlorine) ethylamino 1,4-benzoquinone
Red solid, yield 48%, m.p.102.9-103.4 DEG C
1H NMR(400MHz,CDCl3) δ 6.27 (s, 1H), 6.13 (br, 1H), 5.87 (ddt, J=16.7,10.1,
6.4Hz, 1H), 5.53 (s, 1H), 5.40 (d, J=17.0Hz, 1H), 5.29 (d, J=10.1Hz, 1H), 3.72 (t, J=
5.8Hz, 2H), 3.52 (dd, J=11.8,5.9Hz, 2H), 3.47 (d, J=6.4Hz, 2H)；13C NMR(101MHz,CDCl3)δ
181.4,178.8,158.1,147.0,130.2,120.6,120.0,97.8,43.9,41.3,33.4；HRMS(ESI):m/z
calcd for C11H13ClNO2S[M+H]+:258.03500,found:258.03482.
Test example 1
The activity of the compound in the embodiment of the present invention is determined using attached cell mtt assay, is comprised the following steps that described.
In vitro culture cervical cancer cell lines Hela, stomach cancer cell line BGC-823, lung cancer cell types and prostate cancer are thin
Born of the same parents' strain PC3.After cell growth to exponential phase, cell is collected, 1000rpm is centrifuged 5 minutes, abandoning supernatant, with appropriate training
Foster base is suspended, adjustment cell concentration to 3 × 104/ml.By cell suspension inoculation into 96 porocyte culture plates, per hole 100
μ l, be put into cell culture incubator (37 DEG C, 5%CO2) in culture 24h after, add medicine to be measured (from 10-4~102Three are selected in μM
Concentration, not to be：1×10-1μM、1μM、10μM).After cultivating 72h in incubator, the 5mg/ml μ l of MTT 20 are added per hole, in
37 DEG C of placement 3h.150 μ l DMSO are added per hole, 37 DEG C of shaking tables vibrate 5min, and 492nm/620nm surveys absorbance (OD).Gained knot
Fruit is summarized in table 1 below and table 2.
Table 1
Table 2
Test example 2
The activity of the compound in the embodiment of the present invention is determined using attached cell mtt assay, is comprised the following steps that described.
Cultured Lung Carcinoma Cell strain A549 and Prostatic cancer cell lines PC3.After cell growth to exponential phase, collect
Cell, 1000rpm are centrifuged 5 minutes, abandoning supernatant, suspended with appropriate culture medium, adjustment cell concentration to 3.5~4.5
×104/ml.By cell suspension inoculation into 96 porocyte culture plates, per the μ l of hole 100, be put into cell culture incubator (37 DEG C, 5%
CO2) in culture 24h after, add medicine to be measured (from 10-4~102Five concentration are selected in μM, not to be：1×10-2μM、1×
10-1μM、1μM、10μM、1×101.5μM).Control group (Doxorubicin) adds DMSO, and (final concentration of 0.5%), each group are all provided with 3
Multiple holes.After cultivating 72h in incubator, the 5mg/ml μ l of MTT 20 are added per hole, 3h is placed in 37 DEG C.150 μ are added per hole
LDMSO, 37 DEG C of shaking tables vibrate 5min, and 492nm/620nm surveys absorbance (OD).Calculated with PrismGraphpad statistical softwares
IC50 values (by μM in terms of).Acquired results are summarized in Table 3 below.
Table 3
Claims (12)
1. compound or its pharmaceutically acceptable salt shown in logical formula (I)：
Wherein, R and R1It is independently selected from by hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, aryl, heteroaryl
Base, aryl alkyl, heteroaryl alkyl, heterocyclic radical, cycloheteroalkylalkyl, alkoxy, cycloalkyloxy, aryloxy, alkyl sulfenyl, ring
Alkyl sulfenyl, artyl sulfo, alkoxy carbonyl, aryloxycarbonyl, acyl group, Thioacyl, acyloxy, amide groups, urea groups,
Sulfinyl, alkyl sulphonyl, aryl sulfonyl, haloalkyl, carbamyl, cyano group, isocyano group, nitro, nitroso, sulphur cyanogen
The group that base, isothiocyano, hydrazide group, sulfanyl, sulfo group and monosilane are formed, above-mentioned group is optionally by one or more independent
Ground is selected from by halogen, alkyl, alkoxy, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, aryl, heteroaryl, aryl alkyl, heteroaryl
Base alkyl, heterocyclic radical, cycloheteroalkylalkyl, alkoxy, cycloalkyloxy, aryloxy, alkyl sulfenyl, cycloalkylsulfanyl, aryl sulphur
Base, alkoxy carbonyl, aryloxycarbonyl, acyl group, Thioacyl, acyloxy, amide groups, urea groups, sulfinyl, alkyl sulphur
Acyl group, aryl sulfonyl, haloalkyl, carbamyl, cyano group, isocyano group, nitro, nitroso, thiocyanogen, isothiocyano, acyl
Group substitution in the group that diazanyl, sulfanyl, sulfo group and monosilane are formed；Or R and R1The carbon carbon connected together with them
Double bond is collectively forming 5-7 member unsaturated cyclic groups, and the unsaturated cyclic group optionally contains 1-3 hetero atom, and appoints
Choosing is independently selected by one or more from by halogen, alkyl, alkoxy, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, aryl, miscellaneous
Aryl, aryl alkyl, heteroaryl alkyl, heterocyclic radical, cycloheteroalkylalkyl, alkoxy, cycloalkyloxy, aryloxy, alkyl sulfenyl,
Cycloalkylsulfanyl, artyl sulfo, alkoxy carbonyl, aryloxycarbonyl, acyl group, Thioacyl, acyloxy, amide groups, urea
Base, sulfinyl, alkyl sulphonyl, aryl sulfonyl, haloalkyl, carbamyl, cyano group, isocyano group, nitro, nitroso,
Group substitution in the group that thiocyanogen, isothiocyano, hydrazide group, sulfanyl, sulfo group and monosilane are formed；And
R2And R3It is independently selected from by hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, aryl, aryl alkyl, alcoxyl
Base, cycloalkyloxy, aryloxy, alkyl sulfenyl, cycloalkylsulfanyl, artyl sulfo, Thioacyl, hydrazide group and sulfanyl institute group
Into group, above-mentioned group is optionally independently selected by one or more from by halogen, hydroxyl, alkyl, hydroxy alkyl, alkenyl, alkynes
Base, alkoxy, hydroxy alkoxy base, alkoxy carbonyl group, alkyl sulfenyl, aryl, hydroxyaryl, heteroaryl, heterocyclic radical, oxo heterocycle
Base, amide groups, alkyl sulphonyl, alkoxyphosphonyl groups, aryloxy, cycloalkylsulfanyl, artyl sulfo, Thioacyl, nitro,
Group substitution in the group that nitroso, hydrazide group, sulfanyl and monosilane are formed；Or R2And R3Connected together with them
Nitrogen-atoms is collectively forming 5-7 circle heterocycles bases, above-mentioned heterocyclic radical be optionally independently selected by one or more from by hydroxyl, halogen,
Alkyl, cycloalkyl, alkenyl, cycloalkenyl group, alkynyl, hydroxy alkyl, aryl alkyl, heteroaryl alkyl, heterocyclic radical, cycloheteroalkylalkyl,
Alkoxy, cycloalkyloxy, aryloxy, alkyl sulfenyl, cycloalkylsulfanyl, artyl sulfo, alkoxy carbonyl, aryloxy carbonyl
Base, acyl group, Thioacyl, acyloxy, amide groups, urea groups, sulfinyl, alkyl sulphonyl, aryl sulfonyl, alkyl halide
Base, carbamyl, cyano group, isocyano group, nitro, nitroso, thiocyanogen, isothiocyano, hydrazide group, sulfanyl, sulfo group and first silicon
Group substitution in the group that alkane is formed.
2. compound as claimed in claim 1 or its pharmaceutically acceptable salt, wherein, R and R1Be independently selected from by
Hydrogen, halogen, C1-C4Alkyl, C1-C4The group that alkoxy, phenyl and six membered heteroaryl are formed, above-mentioned C1-C4Alkyl, C1-C4Alcoxyl
Base, phenyl and six membered heteroaryl are optionally independently selected by one or more from by halogen, C1-C4Alkyl and C1-C4Alkoxy institute
Group substitution in the group of composition；Or R and R1The carbon-carbon double bond connected together with them is collectively forming 5-7 member cycloalkenyls, institute
State 5-7 member cycloalkenyls and optionally contain 1 hetero atom, and be optionally independently selected by one or more from by halogen, C1-C4Alkane
Base and C1-C4Group substitution in the group that alkoxy is formed.
3. compound as claimed in claim 2 or its pharmaceutically acceptable salt, wherein, R and R1Be independently selected from by
The group that hydrogen, chlorine, methyl, phenyl and pyridine radicals are formed, above-mentioned methyl, phenyl and pyridine radicals optionally by it is one or more independently
Group substitution in the group being made up of chlorine and methoxyl group；Or R and R1The carbon-carbon double bond connected together with them is total to
Similar shape is into cyclohexenyl group.
4. compound or its pharmaceutically acceptable salt as any one of claim 1-3, wherein, R2And R3Each solely
On the spot it is selected from by hydrogen, C1-C4Alkyl, C1-C4The group that alkoxy, 5-7 members cycloalkyl and phenyl are formed, above-mentioned C1-C4Alkyl,
C1-C4Alkoxy, 5-7 members cycloalkyl and phenyl are independently selected by one or more from by halogen, hydroxyl, C1-C4Alkyl, hydroxyl
Base C1-C4Alkyl, C2-C4Alkenyl, C1-C4Alkoxy, hydroxyl C1-C4Alkoxy, C1-C4Alkoxy carbonyl group, C1-C4Alkyl sulfenyl, benzene
Base, hydroxy phenyl, 5-7 unit's heteroaryls, 5-7 circle heterocycles base, 5-7 member oxo heterocycles base, C1-C4Amide groups, C1-C4Alkyl sulfonyl
Base, C1-C4Group substitution in the group that alkoxyphosphonyl groups are formed；Or R2And R3The nitrogen-atoms connected together with them is total to
With 5-6 circle heterocycles bases are formed, above-mentioned heterocyclic radical is optionally independently selected by one or more from by hydroxyl, hydroxyl C1-C4Alkyl and
C1-C4Group substitution in the group that alkyl sulphonyl is formed.
5. compound as claimed in claim 4 or its pharmaceutically acceptable salt, wherein, R2And R3It is independently selected from
By hydrogen, C1-C4The group that alkyl, cyclohexyl and phenyl are formed, above-mentioned C1-C4Alkyl, cyclohexyl and phenyl are by one or more only
On the spot it is selected from by chlorine, hydroxyl, methyl, hydroxymethyl, pi-allyl, C1-C2Alkoxy, hydroxyl-oxethyl, carbethoxyl group, first sulphur
Base, phenyl, hydroxy phenyl, pyridine radicals, furyl, tetrahydrofuran base, oxoimidazolidinyl, acetamido, mesyl, diethyl
Group substitution in the group that epoxide phosphono is formed；Or R2And R3The nitrogen-atoms connected together with them is collectively forming tetrahydrochysene
Pyrrole radicals, piperidyl or piperazinyl, above-mentioned nafoxidine base, piperidyl or piperazinyl are optionally independently selected by one or more from
Group substitution in the group being made up of hydroxyl, hydroxymethyl and mesyl.
6. compound or its pharmaceutically acceptable salt as any one of claim 1-3, wherein, R2And R3Each solely
On the spot be selected from by hydrogen, benzyl, methoxy-propyl, cyclohexyl, normal-butyl, the tert-butyl group, hydroxypropyl, ethoxycarbonyl-ethyl,
Methylthio, pi-allyl, picolyl, furfuryl, hydroxyethyl, hydroxybutyl, dihydroxypropyl, hydroxy ethoxy second
Base, tetrahydrofuran ylmethyl, hydroxy-cyclohexyl, hydroxyphenylmethyl, phenyl (methylol) methyl, acetamido ethyl, oxo miaow
Oxazolidinyl ethyl, methylsulfonylethyl, diethoxy propyl group, diethoxy phosphonium mesitoyl base ethyl, aminomethyl phenyl and chloroethyl institute group
Into group；Or R2And R3The nitrogen-atoms connected together with them is collectively forming hydroxy piperidine base, methylol nafoxidine base, first
Sulfonyl piperazinium base.
7. compound as claimed in claim 1 or its pharmaceutically acceptable salt, wherein, the compound is selected from by following
The group that compound (1) is formed to (41)：
(1) 2- allyls sulfenyl -5- benzyls amino 1,4-benzoquinone；
(2) the amino 1,4-benzoquinone of 2- allyls sulfenyl -5- (3- methoxyl groups) third；
(3) 2- allyls sulfenyl -5- Cyclohexylamino 1,4-benzoquinone；
(4) 2- allyls sulfenyl -5- n-butyl amines base 1,4-benzoquinone；
(5) the tertiary fourth amino 1,4-benzoquinone of 2- allyls sulfenyl -5-；
(6) the amino 1,4-benzoquinone of 2- allyls sulfenyl -5- (2- hydroxyls) third；
(7) 3- (4- (allyl sulfenyl) -5- (2- carbethoxyl groups) ethylamino 1,4-benzoquinone；
(8) the amino 1,4-benzoquinone of 2- allyls sulfenyl -5- (3- methyl mercaptos) third；
(9) 2- allyls sulfenyl -5- allylamino 1,4-benzoquinone；
(10) 2- allyls sulfenyl -5- (3- picolyls) amino 1,4-benzoquinone；
(11) 2- allyls sulfenyl -5- (2- furfuryls) amino 1,4-benzoquinone；
(12) 2- allyls sulfenyl -5- (4- hydroxyls) piperidyl 1,4-benzoquinone；
(13) the amino 1,4-benzoquinone of 2- (2- methyl) allyl sulfenyls -5- (2- hydroxyls) third；
(14) 2- (but-2-ene -1- bases) sulfenyl -5- (2- hydroxyls) the third amino 1,4-benzoquinone；
(15) 2- (cyclohexene -2- bases) sulfenyl -5- (2- hydroxyls) the third amino 1,4-benzoquinone；
(16) the amino 1,4-benzoquinone of 2- (2- chlorine) allyl sulfenyls -5- (2- hydroxyls) third；
(17) the amino 1,4-benzoquinone of 2- (2- phenyl) allyl sulfenyls -5- (2- hydroxyls) third；
(18) the amino 1,4-benzoquinone of 2- (3- phenyl) allyl sulfenyls -5- (2- hydroxyls) third；
(19) 2- (3- (2- methoxyl groups) phenyl) the third amino 1,4-benzoquinone of allyl sulfenyl -5- (2- hydroxyls)；
(20) 2- (3- (4- fluorine) phenyl) the third amino 1,4-benzoquinone of allyl sulfenyl -5- (2- hydroxyls)；
(21) 2- (3- (pyridin-3-yl)) allyl sulfenyl -5- (2- hydroxyls) the third amino 1,4-benzoquinone；
(22) 2- allyls sulfenyl -5- (2- hydroxyls) ethylamino 1,4-benzoquinone；
(23) the amino 1,4-benzoquinone of 2- allyls sulfenyl -5- (3- hydroxyls) third；
(24) 2- allyls sulfenyl -5- (4- hydroxyls) fourth amino 1,4-benzoquinone；
(25) the amino 1,4-benzoquinone of 2- allyls sulfenyl -5- (2,3- dihydroxy) third；
(26) 2- allyls sulfenyl -5- (2- (2- hydroxyls) ethyoxyl) ethylamino 1,4-benzoquinone；
(27) 2- allyls sulfenyl -5- ((2- methylols) nafoxidine -1- bases) 1,4-benzoquinone；
(28) 2- allyls sulfenyl -5- (tetrahydrofuran -2- bases) methylamino 1,4-benzoquinone；
(29) 2- allyls sulfenyl -5- (trans -4- hydroxyls) Cyclohexylamino 1,4-benzoquinone；
(30) 2- allyls sulfenyl -5- (2- hydroxyls) Cyclohexylamino 1,4-benzoquinone；
(31) 2- allyls sulfenyl -5- (4- hydroxyls) aminotoluene base 1,4-benzoquinone；
(32) 2- allyls sulfenyl -5- (2- hydroxyls) aminotoluene base 1,4-benzoquinone；
(33) 2- allyls sulfenyl -5- (2- hydroxyl -1- phenyl) ethylamino 1,4-benzoquinone；
(34) 2- allyls sulfenyl -5- (2- acetylaminos) ethylamino 1,4-benzoquinone；
(35) 2- allyls sulfenyl -5- (2- imidazolone -1- bases) ethylamino 1,4-benzoquinone；
(36) 2- allyls sulfenyl -5- (1- mesyls) piperazine -4- base 1,4-benzoquinone；
(37) 2- allyls sulfenyl -5- (2- mesyls) ethylamino 1,4-benzoquinone；
(38) the amino 1,4-benzoquinone of 2- allyls sulfenyl -5- (3,3- diethoxies) third；
(39) 1- (4- allyl sulfenyl -3,6- dioxo -1,4- cyclohexadienyls) amino-ethyl diethyl phosphate；
(40) 2- allyls sulfenyl -5- p-totuidines base 1,4-benzoquinone；And
(41) 2- allyls sulfenyl -5- (2- chlorine) ethylamino 1,4-benzoquinone.
8. a kind of pharmaceutical composition, described pharmaceutical composition include：Compound any one of claim 1-7 or its pharmacy
Upper acceptable salt；And pharmaceutically acceptable carrier.
9. preparing the method for compound any one of claim 1-7, methods described is included as follows by hydroquinones, raw material
A and raw material B react in the presence of the NaCl aqueous solution, NaI and organic nitrile：
Wherein each substituent is as defined in logical formula (I).
10. method as claimed in claim 9, wherein, the organic nitrile is CH3CN。
11. the compound and its pharmaceutically acceptable salt any one of claim 1-7 are being prepared for antitumor
Purposes in terms of medicine.
12. purposes as claimed in claim 11, the tumour be selected from by prostate cancer, lung cancer, breast cancer, liver cancer, stomach cancer,
The group that cervical carcinoma, colon cancer and epithelioma are formed.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5565489A (en) * | 1993-09-22 | 1996-10-15 | Kyowa Hakko Kogyo Co., Ltd. | Epoxycyclohexenedione derivatives |
| WO1998017629A1 (en) * | 1996-10-24 | 1998-04-30 | Kyowa Hakko Kogyo Co., Ltd. | 1,4-benzoquinone derivatives |
| WO2005115145A2 (en) * | 2004-05-20 | 2005-12-08 | Wyeth | Quinone substituted quinazoline and quinoline kinase inhibitors |
-
2015
- 2015-04-24 CN CN201510197566.2A patent/CN106146367B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5565489A (en) * | 1993-09-22 | 1996-10-15 | Kyowa Hakko Kogyo Co., Ltd. | Epoxycyclohexenedione derivatives |
| WO1998017629A1 (en) * | 1996-10-24 | 1998-04-30 | Kyowa Hakko Kogyo Co., Ltd. | 1,4-benzoquinone derivatives |
| WO2005115145A2 (en) * | 2004-05-20 | 2005-12-08 | Wyeth | Quinone substituted quinazoline and quinoline kinase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| "一锅法"合成N,S-取代的对苯醌类衍生物;卢艺欢 等;《中国化学会▪全国第十一届有机合成化学学术研讨会》;20141016;第109页 * |
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