CN110386881A - Diaryl ethylene compounds and its pharmaceutical composition and its application - Google Patents

Diaryl ethylene compounds and its pharmaceutical composition and its application Download PDF

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Publication number
CN110386881A
CN110386881A CN201811600348.9A CN201811600348A CN110386881A CN 110386881 A CN110386881 A CN 110386881A CN 201811600348 A CN201811600348 A CN 201811600348A CN 110386881 A CN110386881 A CN 110386881A
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compound
ethylene compounds
diaryl ethylene
diaryl
preparation
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CN110386881B (en
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左之利
孙威
孔德信
彭佳乐
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Kunming Institute of Botany of CAS
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Kunming Institute of Botany of CAS
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/35—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to a kind of diaryl ethylene compounds and its pharmaceutical compositions and its application, are related to pharmaceutical technology field.The present invention provides a kind of diaryl ethylene compounds；Shown in the general structure of diaryl ethylene compounds such as formula (I):Diaryl ethylene compounds proposed by the present invention have apparent monoamine oxidase B (MAO-B) inhibiting effect, can be used for preparing the drug of monoamine oxidase inhibitors B, anti-Parkinson disease.The present invention also provides using above-mentioned diaryl ethylene compounds as the pharmaceutical composition of active constituent, which can be used as monoamine oxidase B (MAO-B) inhibitor, parkinsonism (PD) therapeutic agent.In addition, the structure novel of diaryl ethylene compounds proposed by the present invention, being chemically readily synthesized, inexpensive and Small side effects.

Description

Diaryl ethylene compounds and its pharmaceutical composition and its application
Technical field
The present invention relates to a kind of pharmaceutical technology fields, more particularly to a kind of diaryl ethylene compounds, are with them The pharmaceutical composition of active constituent and they preparation monoamine oxidase B (Monoamine Oxidase B, MAO-B) inhibit Agent and the application in the drug of preparation treatment parkinsonism (Parkinson ' s Disease, PD).
Background technique
Parkinson's disease (Parkinson ' s disease, PD) is a kind of common Neuro-degenerative disease, average Age of onset is 60 years old or so, seriously jeopardizes the health of the elderly, causes tremendous influence to society and economy.Parkinson's disease is most Main pathological change is that the denaturation of basal ganglion nigral dopamine (dopamine, DA) serotonergic neuron is dead, is drawn therefrom Striatum DA level conspicuousness is played to reduce and cause a disease.
Monoamine oxidase (Monoamine Oxidase, MAO) is that Monoamines oxidative deamination is catalyzed in human body Enzyme, the product of oxidative deamination are corresponding aldehyde, amine and hydrogen peroxide.According to the difference of substrate, monoamine oxidase is divided into MAO-A and two kinds of MAO-B.MAO-B has a large amount of distributions at the basal ganglion position of brain tissue, and activity increase with the age and Increase.Since MAO-B can be metabolized DA, the DA missing of PD patient's brain region of interest has been aggravated.In addition, since MAO-B is catalyzed Reacting the aldehyde generated and hydrogen peroxide has a neurotoxicity, and PD patient's black substance position aldehyde dehydrogenase deficiency enhance by Neurotoxicity caused by MAO-B catalysis is reacted.Therefore, inhibit MAO-B can by increase in brain the monoamines neurotransmitter such as DA and It reduces by two kinds of approach of neurotoxicity and treats PD.
The main reason for early stage yoke MAO inhibitor is applied is that patient uses irreversible and non-selective MAO inhibitor When need to strictly observe low junket diet policy, prevent due to intake tyrasamine triggering mortality hypertension.But deeply with research It was found that MAO-B ratio and characteristic distributions in human body, typically now think that reversible and selective MAO-B inhibitor is treated in PD It is safe and acceptable.Currently, not yet in China, approval is applied to clinical treatment to highly-safe MAO-B inhibitor.Therefore, Develop it is a kind of meet above-mentioned standard, with become highly selective MAO-B inhibitor potentiality new structure framework compound be Urgently need.
Summary of the invention
In view of this, the present invention provides a kind of diaryl ethylene compounds and its pharmaceutical composition and its application, mainly It is designed to provide the application with diaryl ethylene compounds inhibitor molecules in anti-Parkinson disease, exploitation has similar bone The lead compound of frame.The present invention provides diaryl ethylene compounds in preparation monoamine oxidase inhibitors B, prepares anti-pa Application in the drug of the gloomy disease of gold.
In order to achieve the above objectives, present invention generally provides following technical solutions:
On the one hand, the embodiment of the present invention provides a kind of diaryl ethylene compounds, which is characterized in that the diaryl Shown in the general structure of ethylene compounds such as formula (I):
In formula (I), W is one of following group:
Wherein, R1, R2, R3, R4, R5, R6, R7 are mutually independent selected from one of following group :-H ,-CH3、-CH2CH3、- Ph,-p-Me-Ph；
In formula (I), Ar1, Ar2 are mutually independent selected from one of following group:
Wherein, R8, R9 are mutually independent selected from one of following group :-H ,-CH3、-CH2CH3、-CH2CH2CH3、-CH (CH3)2、-C(CH3)3、-CH2OH、-CH2NH2、-CH(CH3)NH2、-OH、-OCH3、-OCH2CH3、-OCH(CH3)2、-CF3、- CHF2、-CN、-F、-Cl、-Br、-I、-NO2、-N(CH3)2、-NH2、-NHCH3、-NHAc、-NHSO2CH3、-NHCOCF3；
Wherein, X, Y, Z are mutually independent selected from one of following group:
Wherein, R10 is one of following group :-H ,-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、- CH2OH、-CH2NH2、-CH(CH3)NH2、-OH、-OCH3、-OCH2CH3、-OCH(CH3)2、-CF3、-CHF2、-CN、-F、-Cl、- Br、-I、-NO2、-N(CH3)2、-NH2、-NHCH3、-NHAc、-NHSO2CH3、-NHCOCF3、
Wherein, R11 is one of following group:
-H、-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2OH、-CH2NH2、-CH(CH3)NH2、- CH2CH2NH2、-CH2CH2OH。
Preferably, the diaryl ethylene compounds are one of following compounds:
On the other hand, the embodiment of the present invention provides a kind of pharmaceutical composition, wherein on described pharmaceutical composition includes: The diaryl ethylene compounds and at least one pharmaceutically acceptable auxiliary material stated.
Preferably, in described pharmaceutical composition containing 0.1-99% diaryl ethylene compounds.
Preferably, in described pharmaceutical composition containing 0.5-90% diaryl ethylene compounds.
In another aspect, above-mentioned diaryl ethylene compounds are preparing the application in monoamine oxidase B inhibitors.It is above-mentioned Diaryl ethylene compounds preparation treatment parkinsonism drug in application.
In another aspect, the preparation method of diaryl ethylene compounds 8, wherein
The diaryl ethylene compounds 83,144,145,146,147,148,149,150,151,152,153,154, 155,156,157,158,159,160,161 to prepare equation as follows:
Wherein, E1 is one of following group:
Wherein, E2 is one of following group:
And/or
The diaryl ethylene compounds 162,163,164,165 to prepare equation as follows:
Wherein, E3 is one of following group:
E4 is one of following group:
Preferably, the diaryl ethylene compounds 83,144,145,146,147,148,149,150,151,152, 153,154,155,156,157,158,159,160,161 preparation step is as follows:
It is added into methanol or ethyl alcoholSodium ethoxide stirs setting time, is filtered processing, Obtain solid product；
With ethanol washing solid product, after drying process, diaryl ethylene compounds are obtained.
The preparation step of the preferred diaryl ethylene compounds 162,163,164,165 is as follows:
It is added into methanol or ethyl alcoholAfter sodium ethoxide, setting time is stirred, is purified (e.g., Silica gel column chromatography separating purification), obtain solid product；
After carrying out removing Boc protection group reaction to solid product, diaryl ethylene compounds are obtained.
By above-mentioned technical proposal, diaryl ethylene compounds of the invention and its pharmaceutical composition and its application are at least With following the utility model has the advantages that
The diaryl ethylene compounds in formula (I) that the embodiment of the present invention proposes are inventors by studying for a long period of time It finds for the first time and it is demonstrated with ammoxidation single enzyme B (MAO-B) inhibitory activity by active testing；And formula (I) of the invention Compound have as highly selective MAO-B inhibitor potentiality (this be present invention firstly provides, the prior art is never reported It crosses).The structure novel of diaryl ethylene compounds in formula (I) proposed by the present invention is chemically readily synthesized, inexpensive And Small side effects.Meanwhile the invention also provides the diaryl ethylene compounds in formula (I) as ammoxidation single enzyme B (MAO- B) the new application of target inhibitor, parkinsonism drug.
The above description is only an overview of the technical scheme of the present invention, in order to better understand the technical means of the present invention, And can be implemented in accordance with the contents of the specification, the following is a detailed description of the preferred embodiments of the present invention and the accompanying drawings.
Detailed description of the invention
Fig. 1 is a kind of diaryl ethylene compounds 83 of the embodiment of the present invention offer to ammoxidation single enzyme B (MAO-B) External suppression curve figure；
Fig. 2 is a kind of diaryl ethylene compounds 144 of the embodiment of the present invention offer to ammoxidation single enzyme B (MAO- B external suppression curve figure)；
Fig. 3 is a kind of diaryl ethylene compounds 145 of the embodiment of the present invention offer to ammoxidation single enzyme B (MAO- B external suppression curve figure)；
Fig. 4 is a kind of diaryl ethylene compounds 146 of the embodiment of the present invention offer to ammoxidation single enzyme B (MAO- B external suppression curve figure).
Specific embodiment
It is of the invention to reach the technical means and efficacy that predetermined goal of the invention is taken further to illustrate, below in conjunction with Specific embodiment, structure, feature and its effect applied according to the present invention is described in detail such as in attached drawing and preferred embodiment Afterwards.In the following description, what different " embodiment " or " embodiment " referred to is not necessarily the same embodiment.In addition, one or more Special characteristic, structure or feature in a embodiment can be combined by any suitable form.
Embodiment 1
Part diaryl ethylene compounds of the invention purchased from specs company, Holland (network address: http: // Www.specs.com), number is as shown in table 1 accordingly in library for the diaryl ethylene compounds of this part:
Table 1 is corresponding number of the part diaryl ethylene compounds in library
Compound Number Compound Number Compound Number
66 AO-289/25117029 75 AB-131/06806028 93 AJ-291/34003011
67 AM-814/41094729 76 AA-516/12432405 94 AG-777/36178018
68 AB-131/42301429 78 AG-690/37079203 103 AA-504/06813049
69 AB-131/42300921 80 AN-970/40920809 107 AT-051/43422454
70 AB-131/42300746 82 AB-131/42302837 108 AE-641/02580034
71 AB-131/40897212 84 AI-211/09901015 114 AG-664/02670043
72 AB-131/40897213 85 AG-690/11665343 116 AE-641/01920053
73 AB-131/40897214 88 AG-690/12135048 117 AE-641/02517058
74 AB-131/40897238 92 AB-016/30007056 120 AP-406/42800673
Embodiment 2
Originally it applies example and the preparation method of compound 83 and the structure determination data of compound 83 is mainly provided.
The English name of compound 83 is as follows:
(Z)-2-(4-chlorophenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-enenitrile
Compound 83 the preparation method is as follows:
Specific preparation step: in 10mL methanol be added 455mg p-chlorobenzyl cyanide, 0.41mL p-trifluoromethyl benzaldehyde and 21mg sodium ethoxide is stirred at room temperature 2 hours, white solid is obtained by filtration, and with 2mL cold ethanol washing 2 times, is dried to obtain 349mg Compound 83 (yield 38%).
The structure determination data of compound 83 are as follows:
1H NMR(400MHz,CDCl3) δ 7.97 (d, J=8.0Hz, 2H), 7.74 (d, J=8.0Hz, 2H), 7.63 (d, J =8.8Hz, 2H), 7.55 (s, 1H), 7.45 (d, J=8.8Hz, 2H).
Embodiment 3
Originally it applies example and the preparation method of compound 144 and the structure determination data of compound 144 is mainly provided.
The English name of compound 144 is as follows:
(Z)-2-(4-chlorophenyl)-3-[6-(trifluoromethyl)-3-pyridyl]prop-2- enenitrile
Compound 144 the preparation method is as follows:
Specific preparation step: only need to be by the reaction raw materials in the preparation step of compound 83: p-trifluoromethyl benzaldehyde replaces Change 6- (trifluoromethyl) pyridine-3-carbaldehyde into.
The structure determination data of compound 144 are as follows:
1H NMR(400MHz,CDCl3) δ 8.94 (s, 1H), 8.62 (d, J=8.4Hz, 1H), 7.82 (d, J=8.4Hz, 1H), 7.66 (d, J=8.8Hz, 2H), 7.56 (s, 1H), 7.48 (d, J=8.8Hz, 2H).
Embodiment 4
Originally it applies example and the preparation method of compound 145 and the structure determination data of compound 145 is mainly provided.
The English name of compound 145 is as follows:
(Z)-2-(5-chloro-2-pyridyl)-3-[4-(trifluoromethyl)phenyl]prop-2- enenitrile
The preparation step of compound 145: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide is replaced At 2- (5-chloro-2-pyridyl) acetonitrile, other steps are consistent.
Wherein, the structural formula of 2- (5-chloro-2-pyridyl) acetonitrile are as follows:
The structure determination data of compound 145 are as follows:
1H NMR(400MHz,CDCl3) δ 8.60 (d, J=2.0Hz, 1H), 8.50 (s, 1H), 8.07 (d, J=8.4Hz, 2H),7.73-7.82(m,4H)。
Embodiment 5
Originally it applies example and the preparation method of compound 146 and the structure determination data of compound 146 is mainly provided.
The English name of compound 146 is as follows:
(Z)-2-(5-chloro-2-pyridyl)-3-[6-(trifluoromethyl)-3-pyridyl]prop-2- enenitrile
The preparation step of compound 146 is as follows: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, P-trifluoromethyl benzaldehyde, being substituted for 2- (5-chloro-2-pyridyl) acetonitrile, (specific structure is referring to embodiment 4), 6- (trifluoromethyl) pyridine-3-carbaldehyde (specific structure is referring to embodiment 3), other steps It is rapid consistent.
The structure determination data of compound 146 are as follows:
1H NMR(400MHz,CDCl3) δ 9.05 (s, 1H), 8.67 (d, J=8.4Hz, 1H), 8.62 (d, J=2.0Hz, 1H), 8.53 (s, 1H), 7.83 (d, J=7.6Hz, 2H), 7.75 (d, J=8.4Hz, 1H).
Embodiment 6
Originally it applies example and the preparation method of compound 147 and the structure determination data of compound 147 is mainly provided.
The English name of compound 147 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(4-methoxyphenyl)acrylonitrile
The preparation step of compound 147: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4), P-methoxybenzal-dehyde.
The structure determination data of compound 147 are as follows:
1H NMR(400MHz,CDCl3) δ 8.56 (d, J=2.0Hz, 1H), 8.38 (s, 1H), 8.00 (d, J=8.8Hz, 2H), 7.74 (dd, J=8.4,2.4Hz, 1H), 7.67 (d, J=8.8Hz, 1H), 7.00 (d, J=8.8Hz, 2H), 3.89 (s, 3H)。
Embodiment 7
Originally it applies example and the preparation method of compound 148 and the structure determination data of compound 148 is mainly provided.
The English name of compound 148 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-phenylacrylonitrile
The preparation step of compound 148: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4), benzene Formaldehyde.
The structure determination data of compound 148 are as follows:
1H NMR(400MHz,CDCl3) δ 8.59 (d, J=2.0Hz, 1H), 8.46 (s, 1H), 7.99 (dd, J=7.6, 4.0Hz, 2H), 7.77 (dd, J=8.4,2.4Hz, 1H), 7.71 (d, J=8.4Hz, 1H), 7.49 (dd, J=4.8,1.2Hz, 3H)。
Embodiment 8
Originally it applies example and the preparation method of compound 149 and the structure determination data of compound 149 is mainly provided.
The English name of compound 149 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(thiophen-3-yl)acrylonitrile
The preparation step of compound 149: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and Thiophene-3-carbaldehyde (3- thiophenecarboxaldehyde).
The structure determination data of compound 149 are as follows:
1H NMR(400MHz,CDCl3) δ 8.58 (s, 1H), 8.55 (d, J=2.4Hz, 1H), 7.81-7.72 (m, 2H), 7.67-7.62 (m, 2H), 7.19 (dd, J=4.8,4.0Hz, 1H).
Embodiment 9
Originally it applies example and the preparation method of compound 150 and the structure determination data of compound 150 is mainly provided.
The English name of compound 150 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(p-tolyl)acrylonitrile
The preparation step of compound 150: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4), P-tolyl aldehyde.
The structural characterization data of compound 150 are as follows:
1H NMR(400MHz,CDCl3) δ 8.57 (d, J=2.0Hz, 1H), 8.42 (s, 1H), 7.90 (d, J=8.0Hz, 2H), 7.76 (dd, J=8.8,2.4Hz, 1H), 7.69 (d, J=8.4Hz, 1H), 7.30 (d, J=8.0Hz, 2H), 2.43 (s, 3H)。
Embodiment 10
Originally it applies example and the preparation method of compound 151 and the structure determination data of compound 151 is mainly provided.
The English name of compound 151 is as follows:
(Z)-3-(4-bromophenyl)-2-(5-chloropyridin-2-yl)acrylonitrile
The preparation step of compound 151: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and P-bromobenzaldehyde.
The structure determination data of compound 151 are as follows:
1H NMR(400MHz,CDCl3) δ 8.58 (d, J=2.1Hz, 1H), 8.39 (s, 1H), 7.85 (d, J=8.5Hz, 2H), 7.78 (dd, J=8.5,2.4Hz, 1H), 7.71 (d, J=8.4Hz, 1H), 7.63 (d, J=8.5Hz, 2H).
Embodiment 11
Originally it applies example and the preparation method of compound 152 and the structure determination data of compound 152 is mainly provided.
The English name of compound 152 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(4-fluorophenyl)acrylonitrile
The preparation step of compound 152: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and 4-Fluorobenzaldehyde.
The structure determination data of compound 152 are as follows:
1H NMR(400MHz,CDCl3) δ 8.58 (d, J=2.0Hz, 1H), 8.43 (s, 1H), 8.01 (dd, J=8.8, 5.6Hz, 2H), 7.77 (dd, J=8.4,2.4Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 7.18 (t, J=8.6Hz, 2H).
Embodiment 12
Originally it applies example and the preparation method of compound 153 and the structure determination data of compound 153 is mainly provided.
The English name of compound 153 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(pyridin-4-yl)acrylonitrile
The preparation step of compound 153: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and Pyridine-4-carbaldehyde.
Wherein, the structure of pyridine-4-carbaldehyde are as follows:
The structure determination data of compound 153 are as follows:
1H NMR(400MHz,CDCl3) δ 8.78 (d, J=5.6Hz, 2H), 8.61 (d, J=2.0Hz, 1H), 8.41 (s, 1H), 7.82 (dd, J=8.4,2.4Hz, 1H), 7.77 (dd, J=11.2,6.0Hz, 3H).
Embodiment 13
Originally it applies example and the preparation method of compound 154 and the structure determination data of compound 154 is mainly provided.
The English name of compound 154 is as follows:
(Z)-4-(2-(5-chloropyridin-2-yl)-2-cyanovinyl)benzonitrile
The preparation step of compound 154: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4), To itrile group benzaldehyde.
The structure determination data of compound 154 are as follows:
1H NMR(400MHz,CDCl3) δ 8.60 (d, J=2.0Hz, 1H), 8.48 (s, 1H), 8.05 (d, J=8.4Hz, 2H), 7.81 (dd, J=8.4,2.4Hz, 1H), 7.76 (dd, J=14.4,8.4Hz, 3H).
Embodiment 14
Originally it applies example and the preparation method of compound 155 and the structure determination data of compound 155 is mainly provided.
The English name of compound 155 is as follows:
(Z)-3-(2-bromophenyl)-2-(5-chloropyridin-2-yl)acrylonitrile)
The preparation step of compound 155: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and O-bromobenzaldehye.
The structure determination data of compound 155 are as follows:
1H NMR(400MHz,CDCl3) δ 8.72 (s, 1H), 8.63 (d, J=2.0Hz, 1H), 8.11 (d, J=8.0Hz, 1H), 7.79 (dd, J=8.4,2.4Hz, 1H), 7.74-7.69 (m, 2H), 7.46 (t, J=7.6Hz, 1H), 7.36-7.30 (m, 1H)。
Embodiment 15
Originally it applies example and the preparation method of compound 156 and the structure determination data of compound 156 is mainly provided.
The English name of compound 156 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(6-chloropyridin-2-yl)acrylonitrile
The preparation step of compound 156: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and 6-chloropyridine-2-carbaldehyde (6- Chloro-2-Pyridyle formaldehyde).
Wherein, the structural formula of 6-chloropyridine-2-carbaldehyde is as follows:
The structure determination data of compound 156 are as follows:
1H NMR(400MHz,CDCl3) δ 8.75 (d, J=1.6Hz, 1H), 8.60 (d, J=1.2Hz, 1H), 8.45 (s, 1H),7.83-7.80(m,2H),7.78-7.75(m,2H)。
Embodiment 16
Originally it applies example and the preparation method of compound 157 and the structure determination data of compound 157 is mainly provided.
The English name of compound 157 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(furan-2-yl)acrylonitrile
The preparation step of compound 157: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and Furan-2-carbaldehyde.
Wherein, the structural formula of furan-2-carbaldehyde are as follows:
The structure determination data of compound 157 are as follows:
1H NMR(400MHz,CDCl3) δ 8.54 (d, J=2.0Hz, 1H), 8.25 (s, 1H), 7.74 (dd, J=8.4, 2.4Hz, 1H), 7.66 (d, J=8.8Hz, 2H), 7.22 (d, J=3.6Hz, 1H), 6.61 (dd, J=3.2,1.6Hz, 1H).
Embodiment 17
Originally it applies example and the preparation method of compound 158 and the structure determination data of compound 158 is mainly provided.
The English name of compound 158 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(furan-3-yl)acrylonitrile
The preparation step of compound 158: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and Furan-3-carbaldehyde.
Wherein, the structure of furan-3-carbaldehyde are as follows:
The structure determination data of compound 158 are as follows:
1H NMR (400MHz, CDCl3) δ 8.54 (d, J=2.4Hz, 1H), 8.31 (s, 1H), 8.01 (s, 1H), 7.74 (dd, J=8.4,2.4Hz, 1H), 7.62 (d, J=8.4Hz, 1H), 7.54 (s, 1H), 7.28 (s, 1H).
Embodiment 18
Originally it applies example and the preparation method of compound 159 and the structure determination data of compound 159 is mainly provided.
The English name of compound 159 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(2-fluorophenyl)acrylonitrile
The preparation step of compound 159: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and O fluorobenzaldehyde.
The structure determination data of compound 159 are as follows:
1H NMR(400MHz,CDCl3) δ 8.68 (s, 1H), 8.61 (d, J=2.0Hz, 1H), 8.33 (t, J=7.2Hz, 1H), 7.78 (dd, J=8.4,2.4Hz, 1H), 7.72 (d, J=8.4Hz, 1H), 7.48 (td, J=7.6,1.6Hz, 1H), 7.29 (t, J=7.6Hz, 1H), 7.20-7.15 (t, J=9.2Hz, 1H).
Embodiment 19
Originally it applies example and the preparation method of compound 160 and the structure determination data of compound 160 is mainly provided.
The English name of compound 160 is as follows:
(Z)-2-(5-chloropyridin-2-yl)-3-(2-(trifluoromethyl)phenyl) acrylonitrile
The preparation step of compound 160: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and 2-(Trifluoromethyl) benzaldehyde.
The structure determination data of compound 160 are as follows:
1H NMR(400MHz,CDCl3) δ 8.78 (d, J=2.0Hz, 1H), 8.63 (d, J=2.4Hz, 1H), 8.08 (d, J =7.6Hz, 1H), 7.79 (dd, J=8.4,2.8Hz, 2H), 7.75-7.65 (m, 2H), 7.58 (t, J=7.6Hz, 1H).
Embodiment 20
Originally it applies example and the preparation method of compound 161 and the structure determination data of compound 161 is mainly provided.
The English name of compound 161 is as follows:
(Z)-3-(4-chlorophenyl)-2-(5-chloro-2-pyridyl)prop-2-enenitrile
The preparation step of compound 161: by the reaction raw materials in the preparation step of compound 83: p-chlorobenzyl cyanide, to three Methyl fluoride benzaldehyde, is substituted for: 2- (5-chloro-2-pyridyl) acetonitrile (specific structure is referring to embodiment 4) and P-chlorobenzaldehyde.
The structure determination data of compound 161 are as follows:
1H NMR(400MHz,CDCl3) δ 8.54 (d, J=2.0Hz, 1H), 8.37 (s, 1H), 7.89 (d, J=8.5Hz, 2H), 7.74 (dd, J=8.4,2.4Hz, 1H), 7.66 (d, J=8.4Hz, 1H), 7.43 (d, J=8.4Hz, 2H), 7.22 (s, 1H)。
Embodiment 21
Originally it applies example and the preparation method of compound 162 and the structure determination data of compound 162 is mainly provided.
The English name of compound 162 is as follows:
(Z)-3-(6-(aminomethyl)pyridin-3-yl)-2-(4-chlorophenyl)acrylonitrile
The preparation step of compound 162 is similar with the preparation step of compound 83, and difference is: (1) by compound 83 Reaction raw materials: p-trifluoromethyl benzaldehyde is substituted for: tert-butyl N- [(5-formyl-2-pyridyl) methyl] Carbamate；(2) it needs to slough Boc protecting group after reaction, compound 162 can be obtained.
Wherein, the structural formula of tert-butyl N- [(5-formyl-2-pyridyl) methyl] carbamate are as follows:
The structure determination data of compound 162 are as follows:
1H NMR(400MHz,CD3OD) δ 9.02 (s, 1H), 8.44 (q, J=3.45Hz, 1H), 7.91 (s, 1H), 7.75 (d, J=8.64Hz, 2H), 7.57 (d, J=8.24Hz, 1H), 7.50 (d, J=8.64Hz, 2H), 4.23 (d, J=3.52Hz, 2H)。
Embodiment 22
Originally it applies example and the preparation method of compound 163 and the structure determination data of compound 163 is mainly provided.
The English name of compound 163 is as follows:
(Z)-3-(6-(difluoromethyl)pyridin-3-yl)-2-(4-(piperidin-4-yl)phenyl) acryloni trile
The preparation step of compound 163 is similar with the preparation step of compound 83, and difference is: (1) by compound 83 Reaction raw materials: p-chlorobenzyl cyanide, p-trifluoromethyl benzaldehyde are substituted for:
Tert-butyl 4- [4- (cyanomethyl) phenyl] piperidine-1-carboxylate and 6- (difluoromethyl) pyridine-3-carbaldehyde；(2) it needs to slough Boc protecting group after reaction Obtain compound 163.
Wherein, the structural formula of 4- [4- (cyanomethyl) phenyl] piperidine-1-carboxylate are as follows:
Wherein, the structural formula of 6- (difluoromethyl) pyridine-3-carbaldehyde are as follows:
The structure determination data of compound 163 are as follows:
1H NMR(400MHz,CD3OD) δ 8.93 (s, 1H), 8.48 (q, J=3.33Hz, 1H), 7.84 (s, 1H), 7.73 (d, J=8.28Hz, 1H), 7.69 (d, J=8.32Hz, 2H), 7.34 (d, J=8.28Hz, 2H), 6.68 (t, J=55.10Hz, 1H), 3.43 (d, J=12.64Hz, 2H), 3.07 (m, J=6.41Hz, 2H), 2.90 (m, J=4.05Hz, 1H), 2.01 (d, J =13.88Hz, 2H), 1.84 (m, J=6.21Hz, 2H).
Embodiment 23
Originally it applies example and the preparation method of compound 164 and the structure determination data of compound 164 is mainly provided.
The English name of compound 164 is as follows:
(Z)-2-(4-(piperidin-4-yl)phenyl)-3-(6-(trifluoromethyl)pyridin-3-yl) acrylon itrile
The preparation step of compound 164 is similar with the preparation step of compound 83, and difference is: (1) by compound 83 Reaction raw materials: p-chlorobenzyl cyanide, p-trifluoromethyl benzaldehyde are substituted for: tert-butyl 4- [4- (cyanomethyl) Phenyl] piperidine-1-carboxylate (structural formula is referring to embodiment 22) and 6- (trifluoromethyl) Pyridine-3-carbaldehyde (structural formula is referring to embodiment 3)；(2) it needs to slough Boc protecting group after reaction, Compound 164 can be obtained.
The structure determination data of compound 164 are as follows:
1H NMR(400MHz,CD3OD) δ 9.02 (s, 1H), 8.56 (q, J=3.17Hz, 1H), 7.91 (s, 1H), 7.89 (d, J=8.40Hz, 1H), 7.74 (d, J=8.36Hz, 2H), 7.38 (d, J=8.36Hz, 2H), 3.46 (d, J=12.36Hz, 2H), 3.10 (q, J=7.83Hz, 2H), 2.94 (m, J=3.86Hz, 1H), 2.06 (d, J=14.00Hz, 2H), 1.88 (m, J =6.23Hz, 2H).
Embodiment 24
Originally it applies example and the preparation method of compound 165 and the structure determination data of compound 165 is mainly provided.
The English name of compound 165 is as follows:
(Z)-3-(6-methylpyridin-3-yl)-2-(4-(piperidin-4-yl)phenyl) acrylonitrile
The preparation step of compound 165 is similar with the preparation step of compound 83, and difference is: (1) by compound 83 Reaction raw materials: p-chlorobenzyl cyanide, p-trifluoromethyl benzaldehyde are substituted for: tert-butyl4- [4- (cyanomethyl) Phenyl] piperidine-1-carboxylate (structural formula is referring to embodiment 22) and 6-methylpyridine-3- Carbaldehyde；(2) it needs to slough Boc protecting group after reaction, compound 165 can be obtained.
Wherein, the structural formula of 6-methylpyridine-3-carbaldehyde are as follows:
The structural characterization data of compound 165 are as follows:
1H NMR(400MHz,CD3OD) δ 8.95 (d, J=1.44Hz, 1H), 8.77 (q, J=3.45Hz, 1H), 7.84 (s, 1H), 7.82 (d, J=8.64Hz, 1H), 7.67 (d, J=8.32Hz, 2H), 7.33 (d, J=8.32Hz, 2H), 3.40 (d, J= 12.72Hz, 2H), 3.04 (q, J=7.87Hz, 2H), 2.88 (m, J=3.93Hz, 1H), 2.69 (s, 3H), 1.98 (d, J= 13.88Hz, 2H), 1.83 (m, J=6.21Hz, 2H).
By embodiment 2- embodiment 24 it can be seen that diaryl ethylene compounds in formula proposed by the present invention (I) Structure novel is chemically readily synthesized, inexpensive and Small side effects.
Embodiment 25
The compounds of this invention is in 500nM concentration to the inhibiting effect of monoamine oxidase B (MAO-B):
1, experimental principle
Monoamine oxidase B can be catalyzed the degradation of its substrate analogue kynuramine, generate 4- quinolinol.320nM can be passed through The 4- quinolinol that excitation wavelength/400nM launch wavelength detection reaction generates.Compound and the mixed liquor of monoamine oxidase B are 37 DEG C reaction, if compound has inhibiting effect, monoamine oxidase B catalysis substrate analog kynuramine to monoamine oxidase B The amount of degradation will be reduced, and corresponding reaction product 4- quinolinol is reduced, i.e., in 320nM excitation wavelength/400nM launch wavelength Signal value becomes smaller, and screens the compound with inhibitory activity with this.
2, experimental implementation process
1) prepare 1x buffer solution: preparing 1x and react phosphate buffer solution.
2) diluted compounds: prepare the diluted compound solution of 100x DMSO, take 500nL into the every hole of 384 orifice plates.Most Whole DMSO concentration is 1%.
3) prepare enzyme solutions: monoamine oxidase B is added and obtains the enzyme solutions of 2x into 1x reaction buffer solution.
4) prepare substrate solution: substrate is added and obtains the substrate solution of 2x into 1x reaction buffer solution.
5) enzyme solutions of 25 μ L are shifted into the every hole of 384 orifice plates；The 1x reaction buffering of 25 μ L is added in the air in blank control Solution.
6) in incubation at room temperature 15 minutes.
7) substrate solution that 25 μ L are added starts enzyme reaction into the every hole of 384 orifice plates.
8) it is reacted 30 minutes at 37 DEG C.
9) the 2M NaOH solution that 20 μ L are added terminates reaction.
10) data are read in 320nM excitation wavelength/400nM launch wavelength.
3, data processing:
The inhibiting rate for obtaining compound to monoamine oxidase B is calculated as follows in Excel.Calculation formula is as follows:
Inhibiting rate %=(maximum value-experiment value)/(maximum value-blank value) × 100 formula (1)
4, experimental result
Experimental result is as shown in table 2:
Table 2 is for the compounds of this invention in 500nM concentration to the inhibiting rate of monoamine oxidase B (MAO-B)
Compound Inhibiting rate % Compound Inhibiting rate % Compound Inhibiting rate %
66 88 88 94 116 53
69 20 92 28 117 12
75 98 97 50 119 15
76 25 98 97 120 79
78 25 103 23 162 81
80 44 104 39 163 87
82 5 110 53 164 82
83 98 111 37 165 60
84 82 114 2 152 45
144 97 148 95 153 67
145 72 149 74 154 78
146 75 150 66 155 64
147 86 151 42 156 53
157 78 158 25 159 50
160 45 161 66
As can be seen from Table 2: the compound of the present invention is inhibited to monoamine oxidase B, and some compounds pair The inhibiting effect of monoamine oxidase B is stronger.
Embodiment 26:
The compounds of this invention is to monoamine oxidase B (MAO-B) inhibitory activity IC50Measurement:
1, experimental principle (with embodiment 25).
2, experimental implementation process (with embodiment 25).
3, data processing: compound is calculated to the inhibiting rate of monoamine oxidase B in (1) as follows in Excel.
Inhibiting rate %=(maximum value-experiment value)/(maximum value-blank value) * 100 formula (1)
The IC that compound inhibits monoamine oxidase B is calculated as follows (2) in GraphPad Prism 550 Value.
Y=Bottom+ (Top-Bottom)/(1+10 ∧ ((LogIC50- X) * Hill Slope)) formula (2)
In formula (2): Y is inhibiting rate, and X is compound concentration.
4, experimental result
The experimental result of the present embodiment is as shown in table 3:
Table 3 is the compounds of this invention to monoamine oxidase B (MAO-B) inhibitory activity IC50
As can be seen from Table 3: compared with control (Resveratrol resveratrol), the compounds of this invention aoxidizes monoamine Enzyme B (MAO-B) inhibitory activity is preferable.Also, the inhibitory activity of part of compounds is better than clinical application selegiline (selegiline It is the MAO-B inhibitor of clinical use ratified by FDA, first generation irreversible inhibitor)
From Fig. 1 to Fig. 4 it can be seen that the inhibitory activity of the compound of the present invention 83,144,145,146 is preferable.
Embodiment 27:
The compounds of this invention is to monoamine oxidase A (MAO-A) inhibitory activity IC50Measurement:
1, experimental principle (with embodiment 25).
2, experimental implementation process (with embodiment 25).
3, data processing (with embodiment 26).
4, experimental result
The experimental result of the present embodiment is as shown in table 4:
Table 4 is the compounds of this invention to monoamine oxidase A (MAO-A) inhibitory activity IC50
As can be seen from Table 4: compared with control (Resveratrol resveratrol), the compounds of this invention aoxidizes monoamine Enzyme A (MAO-B) inhibitory activity is poor.
To sum up, the diaryl ethylene compounds in formula (I) proposed by the present invention have ammoxidation single enzyme B (MAO-B) suppression System activity, have as highly selective MAO-B inhibitor potentiality (this be present invention firstly provides, the prior art is never reported Road is crossed).Therefore, the invention also provides the diaryl ethylene compounds in formula (I) to be used as ammoxidation single enzyme B (MAO-B) Target inhibitor, parkinsonism drug.
In addition, can directly be used when diaryl ethylene compounds proposed by the present invention are used as drug, it can also be with drug The form of composition uses.When as pharmaceutical composition in use, the pharmaceutical composition contains 0.1-99%, preferably 0.5- 90% diaryl ethylene compounds, remaining is pharmaceutically acceptable, nontoxic to humans and animals and inert pharmaceutically acceptable Auxiliary material (such as: carrier or excipient).Here, pharmaceutically acceptable auxiliaries (carrier or excipient) be it is one or more selected from solid, it is half solid The adjuvant of body and liquid diluent, extra-fill material and pharmaceutical preparation.By the effective extract or active component with unit bodies The form of weight dose uses.Drug of the invention can be administered with two kinds of forms of mouthspray by oral administration.It is oral that its solid can be used Or liquid preparation, such as pulvis, tablet, sugar coated tablet, capsule, tincture, syrup, pill.Mouthspray can with its solid or Liquid preparation.Drug of the present invention can be used for treating parkinsonism.
Example of formulations:
Example of formulations 1:
The compound that Example 1 is bought, or the compound of the present invention is made by embodiment 2-24, by itself and excipient weight It measures the ratio than 1:1 and excipient, pelletizing press sheet is added.
Example of formulations 2:
The compound that Example 1 is bought, or compound is made by embodiment 2-24, by itself and excipient weight ratio 1:2 Ratio be added excipient, pelletizing press sheet.
Example of formulations 3:
The compound that Example 1 is bought, or compound is made by embodiment 2-24, routinely capsule preparations method is made Capsule.
Example of formulations 4:
The compound that Example 1 is bought, or compound is made by embodiment 2-24, then tablet is made as follows:
Example of formulations 5:
Capsule: the compound that Example 1 is bought, or the compound prepared by embodiment 2-24: 100mg, starch: suitable Amount, magnesium stearate: appropriate
Preparation method: compound is mixed with auxiliary agent, and sieving uniformly mixes in suitable container, obtained mixing Object is packed into hard gelatin capsule.
Example of formulations 6:
Nasal spray: the compound that Example 1 is bought, or the compound prepared by embodiment 2-24: 80mg
Preparation method: being added a kind of ingredient every time in the double distilled water of proper volume under stirring, until completely deep solution, so After add another ingredient.After adding water to 2ml, which is filtered on sterilizing filter, is fitted into bottle and according to appropriate Dosage separate.
Example of formulations 7:
Dripping pill: the compound that Example 1 is bought, or the compound prepared by embodiment 2-24: 1g, polyethylene glycol 6000:9g
Preparation method: the preparation of compound and Macrogol 6000 molten liquid: pressing above-mentioned recipe quantity Weigh Compound, is added appropriate Dehydrated alcohol after low-grade fever dissolution, is added in the polyethylene glycol molten liquid of recipe quantity (60 DEG C of water-bath heat preservations), is uniformly mixed, It until ethyl alcohol is waved to the greatest extent, is statically placed in 60 DEG C of water-baths and keeps the temperature 30 minutes, eliminated to bubble, then will eliminate the above-mentioned mixed of bubble Even molten liquid is transferred in surge drum, and under conditions of keeping the temperature 80-85 DEG C, control drop speed is instilled in condensate liquid dropwise, waited cold Solidifying incline condensate liquid completely, collects dripping pill, and drip is net and removes the condensate liquid on ball with filter paper, place in silica gel drier or from It is so dry.
The above described is only a preferred embodiment of the present invention, be not intended to limit the present invention in any form, according to According to technical spirit any simple modification, equivalent change and modification to the above embodiments of the invention, this hair is still fallen within In the range of bright technical solution.

Claims (10)

1. a kind of diaryl ethylene compounds, which is characterized in that the general structure of the diaryl ethylene compounds such as formula (I) shown in:
In formula (I), W is one of following group:
Wherein, R1, R2, R3, R4, R5, R6, R7 are mutually independent selected from one of following group :-H ,-CH3、-CH2CH3、-Ph、- p-Me-Ph；
In formula (I), Ar1, Ar2 are mutually independent selected from one of following group:
Wherein, R8, R9 are mutually independent selected from one of following group :-H ,-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C (CH3)3、-CH2OH、-CH2NH2、-CH(CH3)NH2、-OH、-OCH3、-OCH2CH3、-OCH(CH3)2、-CF3、-CHF2、-CN、- F、-Cl、-Br、-I、-NO2、-N(CH3)2、-NH2、-NHCH3、-NHAc、-NHSO2CH3、-NHCOCF3；
Wherein, X, Y, Z are mutually independent selected from one of following group:
Wherein, R10 is one of following group :-H ,-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2OH、- CH2NH2、-CH(CH3)NH2、-OH、-OCH3、-OCH2CH3、-OCH(CH3)2、-CF3、-CHF2、-CN、-F、-Cl、-Br、-I、- NO2、-N(CH3)2、-NH2、-NHCH3、-NHAc、-NHSO2CH3、-NHCOCF3、
Wherein, R11 is one of following group:
-H、-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2OH、-CH2NH2、-CH(CH3)NH2、- CH2CH2NH2、-CH2CH2OH。
2. diaryl ethylene compounds according to claim 1, which is characterized in that the diaryl ethylene compounds For one of following compounds:
3. a kind of pharmaceutical composition, which is characterized in that described pharmaceutical composition includes: diaryl second of any of claims 1 or 2 Vinyl compound and at least one pharmaceutically acceptable auxiliary material.
4. pharmaceutical composition according to claim 3, which is characterized in that contain 0.1-99% in described pharmaceutical composition Diaryl ethylene compounds.
5. pharmaceutical composition according to claim 4, which is characterized in that contain 0.5-90% in described pharmaceutical composition Diaryl ethylene compounds.
6. diaryl ethylene compounds of any of claims 1 or 2 are preparing the application in monoamine oxidase B inhibitors.
7. application of the diaryl ethylene compounds of any of claims 1 or 2 in the drug of preparation treatment parkinsonism.
8. the preparation method of diaryl ethylene compounds as claimed in claim 2, which is characterized in that
The diaryl ethylene compounds 83,144,145,146,147,148,149,150,151,152,153,154,155, 156,157,158,159,160,161 to prepare equation as follows:
Wherein, E1 is one of following group:
Wherein, E2 is one of following group:
And/or
The diaryl ethylene compounds 162,163,164,165 to prepare equation as follows:
Wherein, E3 is one of following group:
E4 is one of following group:
9. the preparation method of diaryl ethylene compounds according to any one of claims 8, which is characterized in that the diarylethene Compound 83,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160, 161 preparation method includes the following steps:
It is added into methanol or ethyl alcoholSodium ethoxide stirs setting time, is filtered processing, consolidate Body product；
With ethanol washing solid product, after drying process, diaryl ethylene compounds are obtained.
10. the preparation method of diaryl ethylene compounds according to claim 8, which is characterized in that the diaryl The preparation method of ethylene compounds 162,163,164,165 includes the following steps:
It is added into methanol or ethyl alcoholSodium ethoxide stirs setting time, is purified, and obtains solid production Object；
After carrying out removing Boc protection group reaction to solid product, diaryl ethylene compounds are obtained.
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KATO, TETSUZO等: "Synthesis of methylpyridine derivatives. XXV. Synthesis of α-substituted 2-pyridineacetonitriles", 《YAKUGAKU ZASSHI 》 *

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