CN102827131B - Isoflavones amino formate compounds, Preparation Method And The Use - Google Patents
Isoflavones amino formate compounds, Preparation Method And The Use Download PDFInfo
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- CN102827131B CN102827131B CN201210329644.6A CN201210329644A CN102827131B CN 102827131 B CN102827131 B CN 102827131B CN 201210329644 A CN201210329644 A CN 201210329644A CN 102827131 B CN102827131 B CN 102827131B
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Abstract
The invention discloses the novel isoflavones amino formate compounds (I) of a class and pharmacy acceptable salt thereof, also disclose the preparation method of this compounds, and the purposes in preparation and/or prevention nervus retrogression relative disease medicine, include but not limited to the nerve degenerative diseases such as vascular dementia, Alzheimer's disease, parkinsonism, huntington disease, HIV related dementia disorders, multiple sclerosis, progressive lateral sclerosis disease, neuropathic pain, glaucoma.
Description
Technical field
The invention belongs to medicinal chemistry art, relate to the novel isoflavones amino formate compounds of a class (
i) and pharmacy acceptable salt, its preparation method, pharmaceutical composition and preparing the purposes that treats and/or prevents in nervus retrogression relative disease medicine, include but not limited to the nerve degenerative diseases such as vascular dementia, Alzheimer's disease, parkinsonism, huntington disease, HIV related dementia disorders, multiple sclerosis, progressive lateral sclerosis disease, neuropathic pain, glaucoma.
Background technology
Vascular dementia (Vascular Dementia, VD) be the clinical syndrome of intelligence caused by various types of cerebrovascular disease (comprising ischemic cerebrovascular disease, hemorrhagic cerebrovascular disease, acute and hypoxia-induced cerebrovascular disease etc.) and cognition dysfunction, its main clinical manifestation comprises: cognitive ability, memory and social-life ability go down and emotion, personality change, be a kind of chronic progressive disease.In first reason that Asian countries's vascular dementia such as Chinese, Japanese is senile dementia; Along with world population is to the continuous propelling of aging, cerebro-vascular diseases is increasing, and Onset of Vascular Dementia rate has the trend risen gradually, has a strong impact on work and the quality of life of the elderly, and brings heavy economy and mental burden to society and family.Therefore, VD to have become in current geriatrics and psychologic medicine field an important study hotspot.Vascular dementia is complicated due to pathogenesis, there is no the medicine that can block disease progression, and current clinical treatment is to improve brain blood circulation and brain metabolism, and it is main for strengthening brain nutrition.
In recent years, research both at home and abroad shows, the also frequent exception with cholinergic system while VD patients cerebral damage.VD patient's hippocampus ChAT positive neuron and fibre density lower, the ChAT activity decrease of different sites in brain, and the ACh concentration in VD Cerebrospinal Fluid in Patients is starkly lower than normal level, and the degree that its concentration reduces is proportionate with dull-witted severity; And cerebral ischemia can cause acetylcholine esterase active in brain to rise; Meanwhile, also find that some acetylcholinesterase depressant are as HuperzineA and Revastigmine, can protect the neuronal damage that ischemic causes, and the recovery of nerve injury and brain function after cerebral ischemia can be promoted.This shows that acetylcholinesterase depressant also can be used for the treatment of vascular dementia.
Alzheimer's disease (Alzheimer ' s disease, AD, senile dementia) be a kind of central nervous system degenerative disease damaged based on Progressive symmetric erythrokeratodermia cognitive disorder and memory, its sickness rate is in ascendant trend year by year, become the frequently-occurring disease being only second to cardiovascular diseases and cancer, rise to the 4th of the cause of death in developed countries such as America and Europes.According to WHO Report, global over-65s old man has 10% dysnoesia, and wherein 1/2nd dementia occur, more than 85 years old sickness rate nearly 50%.At present, China AD number of patients is more than 5,000,000, and this disease there is no effective treatment means at present, and along with the quickening of China's aging population process, this numeral will be more huge.Because AD clinical manifestation is that memory capability, orientation property, thinking and judgement go down, and activity of daily living reduces, even there is abnormal Behavioral and psychological symptom etc., make patient care difficulty larger, bring heavy burden to society and family, thus, novel senile dementia medicine is researched and developed significant.From the market requirement, " senile dementia report " prediction that world market research and strategist company complete recently, the global marketing volume to senile dementia medicine in 2015 will reach 10,000,000,000 dollars; In China, along with the rapid rising of senile dementia sickness rate, the market also rapid expansion of this kind of medicine.
AD belongs to the disease that many factors causes, pathogeny is complicated, so far also its pathogenesis is not illustrated completely, dissect after death and find cerebral amyloid sample senile plaque (Senile Plaques, SP) and neurofibrillary tangles (Neurofibrillary Tangles, NFT) be the histopathologic change of patient's AD most feature.In recent years, many investigators are devoted to from molecule and cell levels to disclose the pathogeny of AD, propose multiple hypothesis, as: the deposition, Protein tau Hyperphosphorylationof, inflammation, free-radical oxidn, metal ion imbalance etc. of cholinergic neuron damage, amyloid, therefore, the novel therapeutic approach developed for these pathogenesis and means, will be hopeful the state of an illness alleviating and improve AD patient.The medicine of effectively treating AD at present clinically mainly contains two classes: the cholinergic hypothesis that (1) causes cognitive function to be lacked of proper care based on neurotransmitter acetic acid choline deficiency, acetylcholinesterase depressant is adopted to improve second phthalein choline levels in patient's brain, as: Tacrine, Donepezil, Ravastigmine, Galantamine; (2) adopt
n-methyl-
d-aspartic acid (NMDA) acceptor inhibitor reduces glutaminate to the damage of neurocyte, as: Memantine Hydrochloride.But these medicines exist, and action target spot is single, toxic side effect is more, to the problem such as the long-term efficacy of AD patient is not good enough.Therefore, the active demand that research and development have novel mechanism of action, multiaction target spot, low toxic side effect AD medicine not only meet social senilization's process, and there are good market outlook.
Summary of the invention
The object of the invention is to disclose the novel isoflavones amino formate compounds of a class (
i) and pharmacy acceptable salt.
Another object of the present invention is to disclose this quasi-isoflavone amino formate compounds (
i) and the preparation method of pharmacy acceptable salt.
Another object of the present invention be openly to comprise this quasi-isoflavone amino formate compounds (
i) and the pharmaceutical composition of pharmacy acceptable salt.
Another object of the present invention be to disclose this quasi-isoflavone amino formate compounds (
i) and pharmacy acceptable salt preparing the purposes that treats and/or prevents in nervus retrogression relative disease medicine, include but not limited to the nerve degenerative diseases such as vascular dementia, Alzheimer's disease, parkinsonism, huntington disease, HIV related dementia disorders, multiple sclerosis, progressive lateral sclerosis disease, neuropathic pain, glaucoma.
Isoflavones amino formate compounds disclosed in this invention (
i) chemical structure of general formula be:
In formula:
arbe expressed as follows shown
(A)~
(F)middle any structural unit, n=1-2,
R
1and R
2represent H, C independently of one another
1~ C
12alkyl, C
1~ C
6fat alcohol radical or itself and C
1~ C
6ester, C that carboxylic acid is formed
1~ C
6carboxyl or itself and C
1~ C
6the ester that fatty alcohol is formed, benzyl or substituted benzyl, but R
1and R
2be asynchronously H; R
1nR
2also represent that Pyrrolidine ring, morpholine ring, piperidine ring, 4-benzyl piepridine ring, 4-substituted benzyl piperidine ring, piperazine ring, homopiperazine ring, 4-position are by C
1~ C
12the piperazine ring that alkyl replaces or homopiperazine ring, 4-position by benzyl or substituted benzyl the piperazine ring that replaces or homopiperazine ring; Above-mentioned term " substituted benzyl " refer to by phenyl ring by 1-4 to be selected from the group of lower group the benzyl that replaces: F, Cl, Br, I, C
1-4alkyl, C
1-4alkoxyl group, trifluoromethyl, trifluoromethoxy, nitro, amino, carboxyl, hydroxyl, cyano group, these substituting groups can at any possible position of phenyl ring; R
3represent H, C
1~ C
12alkyl, trifluoromethyl.
Isoflavones amino formate compounds disclosed in this invention (
i) prepare by following methods:
In formula: Ar, R
1, R
2identical with above-mentioned chemical structure of general formula with the definition of n.
Above-mentioned chemical equation give isoflavones amino formate compounds (
i) synthetic method, its concrete preparation method is described below:
With " phenolic compound " for starting raw material, under alkalescence and solvent condition, (work as R with carbamyl chlorine derivative or isocyanic ester respectively
1during=H) compounds condensation, can obtain corresponding isoflavones amino formate compounds (
i); Above-mentioned term " phenolic compound " refers to: genistein or derivatives thereof, soybean isoflavones or derivatives thereof; Wherein, reacting solvent for use is: ether, tetrahydrofuran (THF),
n,N-dimethyl formamide, dimethyl sulfoxide (DMSO), methylene dichloride, chloroform, C
3~ C
8aliphatic ketone, benzene, toluene, acetonitrile, pyridine or C
5~ C
8alkane, preferred solvent is:
n,N-dimethyl formamide, acetone, chloroform, acetonitrile, tetrahydrofuran (THF) or pyridine; React alkali used be basic metal or alkaline earth metal hydroxides, basic metal or alkaline earth metal carbonate, basic metal or alkali metal bicarbonates, trimethylamine class or quaternary ammonium bases (as: triethylamine, Tributylamine, trioctylamine, pyridine,
n-methylmorpholine,
n-methyl piperidine, triethylene diamine, TBAH), preferred bases is: sodium bicarbonate, salt of wormwood, potassium hydroxide, triethylamine or pyridine; Phenolic compound: carbamyl chlorine derivative or isocyanate ester compound: the molar feed ratio of alkali is 1.0:1.0 ~ 6.0:1.0 ~ 12.0, and preferred molar feed ratio is 1.0:1.0 ~ 4.5:1.0 ~ 9.0; Temperature of reaction is 0 ~ 130 DEG C, and preferable reaction temperature is room temperature ~ 80 DEG C; Condensation reaction time is 2 hours ~ 7 days, and the preferred reaction time is 3 ~ 24 hours.
According to the method described above gained isoflavones amino formate compounds (
i), work as R
1nR
2represent that piperazine ring, homopiperazine ring, 4-position are by C
1~ C
12the piperazine ring that alkyl replaces or homopiperazine ring, 4-position by benzyl or substituted benzyl the piperazine ring that replaces or homopiperazine ring time, amino owing to containing in this quasi-molecule, this amino is in alkalescence, can obtain acceptable salt on its pharmacology with any suitable acid by pharmaceutically conventional salifying method, described acid is: hydrochloric acid, Hydrogen bromide, nitric acid, sulfuric acid, phosphoric acid, C
1-6aliphatic carboxylic acid (as: formic acid, acetic acid, propionic acid etc.), oxalic acid, phenylformic acid, Whitfield's ointment, toxilic acid, fumaric acid, succsinic acid, tartrate, citric acid, C
1-6alkylsulphonic acid (as: methylsulphonic acid, ethylsulfonic acid etc.), camphorsulfonic acid, Phenylsulfonic acid or tosic acid; In the molecular structure of formed salt, isoflavones amino formate compounds (
i) with acid mol ratio be 1.0:1.0 ~ 3.0.
Pharmaceutical composition disclosed in this invention comprise treatment significant quantity one or more isoflavones amino formate compoundss (
i) or its pharmacy acceptable salt, this pharmaceutical composition can contain one or more pharmaceutically acceptable carrier or vehicle further.Described " treatment significant quantity " refer to cause investigator or doctor for tissue, the biology of system or animal or the medicine of medicine reaction or the amount of medicament; Described " composition " refers to the product by more than one materials or component being mixed; Described " pharmaceutically acceptable carrier " refers to pharmaceutically acceptable material, composition or carrier, as: liquid or solid weighting agent, thinner, vehicle, solvent or packing material, they carry or transport certain chemical substance.
Its desirable ratio of pharmaceutical composition provided by the present invention is, isoflavones amino formate compounds (
i) or its pharmacy acceptable salt account for gross weight than 50% ~ 99.5% as activeconstituents, rest part is for accounting for gross weight than less than 50%.
Isoflavones amino formate compounds disclosed in this invention (
i) and pharmacy acceptable salt carried out following bioactivity screening.
(1) cholinesterase inhibition
Reaction total volume is 4ml, include acetylthiocholine iodide 0.3mmol or sulfur iodide for BuCh 0.4mmol, 0.1 M pH7.4 sodium phosphate buffer 1ml, compound 0.1 ~ 0.5ml, the benefit that adds water comprises rear enzyme-added liquid measure to 4ml(), enzyme liquid 0.1 or 0.2ml is added after 5 minutes in 37 DEG C of insulations, 1ml 3% sodium laurylsulfonate (SDS) termination reaction is added after being incubated 8 minutes again, finally add two (3-carboxyl-4-nitro) phenyl disulfide (i.e. Ellman's reagent) solution colour developing of 1ml 0.2%, produce yellow 5-sulphur-2-nitrophenoxy acid negatively charged ion.Measure optical density(OD) with spectrophotometer in 440nm, all samples is all surveyed two-tube.Not add the mensuration pipe optical density(OD) of compound as 100%, compound determination pipe optical density(OD) compares with it, and the percentage of reduction is enzyme inhibition rate.Each compound is all made into 10
-5mol/L concentration carries out primary dcreening operation, and enzyme inhibition rate reaches more than 50% person and measures its IC
50; Select its enzyme inhibition rate of seven to nine concentration determinations of compound according to primary dcreening operation result, and carry out linear regression with the negative logarithm of this compound volumetric molar concentration and enzyme inhibition rate, volumetric molar concentration when trying to achieve 50% suppression is the IC of this compound
50value.
Measurement result shows, compound disclosed in this invention all has remarkable restraining effect to acetylcholinesterase, its IC
50be 0.01 μM ~ 100 μMs, and positive control medicine---the IC of Rivastigmine
50it is 3.71 μMs; Measurement result also shows compound disclosed in this invention to the inhibit activities of acetylcholinesterase far away higher than the inhibit activities to butyrylcholine esterase, illustrates that compound disclosed in this invention has selective inhibitory to acetylcholinesterase.
(2) compound is to H
2
o
2
the provide protection screening of the PC12 cell injury of induction
The DMEM nutrient solution of PC12 cell containing 10 % calf serums, with 1 × 10
5individual/mL density is inoculated on 96 well culture plates, and inoculation volume is 100 μ L/ holes, puts into subsequently containing 5% CO
237 DEG C of constant incubators in cultivate.Cultivate after 24 hours, (final concentration is 10 to add the compound of respective concentration in administration group
-5mol/L, 10
-6mol/L) 10 μ L/ holes, 2 hours (control group and damage group add 10 μ L/ hole PBS respectively, make its volume keep equal) of preincubate.PC12 cell incubation, after 2 hours, adds 100 μMs of H respectively in administration group and damage group
2o
2damage agent 10 μ L/ hole (control group adds 10 μ L/ hole PBS), after 30 minutes, the RPMI RPMI-1640 all changed into by the nutrient solution of each group without calf serum continues to put into constant incubator cultivation 24 hours, and nutrient solution volume is still 100 μ L/ holes.Continue cultivation after 24 hours, add 5 mg/mL MTT 100 μ L/ holes in each group, carry out viable cell dyeing.After 3 hours, add 100 % DMSO stop buffer 100 μ L/ holes in each group, fully dissolve mixing.The OD value of each group is measured under the wavelength of 490 nm.Test result repeats 3 times, and with Duncan ' s test method statistic, the numeric representation of each group is mean ± S.E.M., and with control group for 100%, administration group and damage class value represent with the per-cent of control group.
Measurement result shows, the PC12 cell injury of compound disclosed in this invention to hydrogen peroxide-induced all has provide protection in various degree.
Embodiment
Can be conducted further description the present invention by the following examples, but scope of the present invention is not limited to following embodiment.One of skill in the art can understand, and under the prerequisite not deviating from the spirit and scope of the present invention, can carry out various change and modification to the present invention.
embodiment 1
7,4 '-two (
n, N-formyl oxygen dimethylamino) preparation of-5-hydroxy-isoflavone (I-C-1)
Genistein (2.0 mmol), K is added in reaction flask
2cO
3(6.0 mmol) and
n,N-dimethyl formamide (20 ml), adds after stirring
n,N-dimethylcarbamyl chloride (6.0 mmol), stirring at room temperature is reacted 24 hours (reaction process TLC follows the tracks of); After reaction terminates, by reaction solution impouring deionized water, with 10%HCl aqueous solution regulator solution pH to acid, the off-white color solid that suction filtration is separated out, through purification by silica gel column chromatography (elutriant: methylene dichloride/acetone=30:1v/v), obtains buff powder solid, yield 60.0%, mp:202 ~ 203 DEG C
1h-NMR (400MHz, CDCl
3)
δ: 12.74 (s, 1H, 5-OH), 7.95 (s, 1H, 2-H), 7.53 (d,
j=8.8Hz, 2H, 2 ', 6 '-H), 7.21 (d,
j=8.8Hz, 2H, 3 ', 5 '-H), 6.82 (d,
j=2.0Hz, 1H, 6-H), 6.61 (d,
j=2.0Hz, 1H, 8-H), 3.11 (s, 6H, 2 × NCH
3), 3.04 (s, 6H, 2 × NCH
3), HR-TOFMS (+Q)
m/z: 413.1353 ([C
21h
20n
2o
7+ H]
+calculated value: 413.1349).
embodiment 2
7,4 '-two (
n-methyl-
n-ethylcarbamoyl oxygen base) preparation of-5-hydroxy-isoflavone (I-C-2)
Operating process, with embodiment 1, just will
n,N-dimethyl formamide acetonitrile substitutes, K
2cO
3substitute with triethylamine,
n,N-dimethylcarbamyl chloride is used
n-methyl-
n-ethylcarbamoyl chlorine substitutes, and obtains buff powder solid, yield 65.0%, mp:165 ~ 166 DEG C,
1h-NMR (400MHz, CDCl
3)
δ: 12.75 (s, 1H, 5-OH), 7.95 (s, 1H, 2-H), 7.53 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.21 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.83 (d,
j=1.6Hz, 1H, 6-H), 6.62 (d,
j=1.6Hz, 1H, 8-H), 3.40 ~ 3.52 (m, 4H, 2 × NCH
2), 3.09 (d,
j=4.4Hz, 3H, NCH
3), 3.01 (d,
j=4.4Hz, 3H, NCH
3), 1.19 ~ 1.27 (m, 6H, 2 × CH
3), HR-TOFMS (+Q)
m/z: 441.1655 ([C
23h
24n
2o
7+ H]
+calculated value: 441.1662).
embodiment 3
7,4 '-two (
n, N-diethylin methanoyl) preparation of-5-hydroxy-isoflavone (I-C-3)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride is used
n,N-diethylamino formyl chloride substitutes, and obtains buff powder solid, yield 61.5%, mp:114 ~ 116 DEG C,
1h-NMR (400MHz, CDCl
3)
δ: 12.74 (s, 1H, 5-OH), 7.94 (s, 1H, 2-H), 7.53 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.21 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.83 (d,
j=2.0Hz, 1H, 6-H), 6.61 (d,
j=2.0Hz, 1H, 8-H), 3.38 ~ 3.46 (m, 8H, 4 × NCH
2), 1.22 ~ 1.28 (m, 12H, 4 × NCH
3), HR-TOFMS (+Q)
m/z: 469.1972 ([C
25h
28n
2o
7+ H]
+calculated value: 469.1975).
embodiment 4
7,4 '-two (
n, N-diisopropylaminoethyl methanoyl) preparation of-5-hydroxy-isoflavone (I-C-4)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride is used
n,N-diisopropylaminoethyl formyl chloride substitutes, and obtains off-white powder solid, yield 53.8%, mp:150 ~ 151 DEG C,
1h-NMR (400MHz, CDCl
3)
δ: 12.75 (s, 1H, 5-OH), 7.94 (s, 1H, 2-H), 7.53 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.21 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.82 (d,
j=2.0Hz, 1H, 6-H), 6.61 (d,
j=2.0Hz, 1H, 8-H), 4.09 ~ 4.14 (m, 2H, 2 × NCH), 4.93 ~ 3.96 (m, 2H, 2 × NCH), 1.35 ~ 1.31 (m, 24H, 8 × CH
3), HR-TOFMS (+Q)
m/z: 525.2607 ([C
29h
36n
2o
7+ H]
+calculated value: 525.2601).
embodiment 5
the preparation of 7,4 '-two (piperidines-1-methanoyl)-5-hydroxy-isoflavone (I-C-5)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride is used
n-piperidine formyl chlorine substitutes, and obtains white powder solid, yield 57.7%, mp:230 ~ 231 DEG C,
1h-NMR (400MHz, CDCl
3) δ: 12.74 (s, 1H, 5-OH), 7.95 (s, 1H, 2-H), 7.52 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.20 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.81 (d,
j=2.0Hz, 1H, 6-H), 6.60 (d,
j=2.0Hz, 1H, 8-H), 3.60 (brs, 4H, 2 × NCH
2), 3.53 (brs, 4H, 2 × NCH
2), 1.62 (m, 12H, 6 × CH
2), HR-TOFMS (+Q)
m/z: 493.1968 ([C
27h
28n
2o
7+ H]
+calculated value: 493.1975).
embodiment 6
7,4 '-two (
n-morpholine methanoyl) preparation of-5-hydroxy-isoflavone (I-C-6)
operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride is used
n-morpholine formyl chloride substitutes, and obtains white powder solid, yield 65.0%, mp:228 ~ 229 DEG C,
1h-NMR (400MHz, CDCl
3)
δ: 12.75 (s, 1H, 5-OH), 7.96 (s, 1H, 2-H), 7.53 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.21 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.82 (d,
j=2.0Hz, 1H, 6-H), 6.61 (d,
j=2.0Hz, 1H, 8-H), 3.76 (s, 8H, 4 × OCH
2), 3.68 (s, 4H, 2 × NCH
2), 3.59 (s, 4H, 2 × NCH
2), HR-TOFMS (+Q)
m/z: 497.1553 ([C
25h
24n
2o
9+ H]
+calculated value: 497.1560).
embodiment 7
7,4 '-two [
n-(4-methyl) piperazine methanoyl] preparation of-5-hydroxy-isoflavone (I-C-7)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride 4-methylpiperazine-1-formyl chloride hydrochloride substitutes, and obtains white powder solid, yield 52.5%, mp:223 ~ 225 DEG C,
1h-NMR (400MHz, CDCl
3)
δ: 12.74 (s, 1H, 5-OH), 7.95 (s, 1H, 2-H), 7.53 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.20 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.81 (d,
j=2.0Hz, 1H, 6-H), 6.61 (d,
j=2.0Hz, 1H, 8-H), 3.71 (brs, 4H, 2 × NCH
2), 3.62 (brs, 4H, 2 × NCH
2), 2.50 (brs, 8H, 4 × NCH
2), 2.37 (s, 6H, 2 × CH
3), HR-TOFMS (+Q)
m/z: 523.2194 ([C
27h
30n
4o
7+ H]
+calculated value: 523.2193).
embodiment 8
7,4 '-two [
n-(4-benzyl) piperazine methanoyl] preparation of-5-hydroxy-isoflavone (I-C-8)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride 4-benzyl diethylenediamine-1-formyl chloride hydrochloride substitutes, and obtains white powder solid, yield 67.8%, mp:213 ~ 215 DEG C,
1h-NMR (400MHz, CDCl
3)
δ: 12.74 (s, 1H, 5-OH), 7.95 (s, 1H, 2-H), 7.52 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.29 ~ 7.35 (m, 10H, Ar-H), 7.19 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.80 (d,
j=2.0Hz, 1H, 6-H), 6.60 (d,
j=2.0Hz, 1H, 8-H), 3.69 (s, 4H, 2 × NCH
2), 3.59 (s, 8H, 4 × NCH
2), 2.53 (s, 8H, 4 × NCH
2), HR-TOFMS (+Q)
m/z: 675.2814 ([C
39h
38n
4o
7+ H]
+calculated value: 675.2819).
embodiment 9
7,4 '-two (
n-Pyrrolidine methanoyl) preparation of-5-hydroxy-isoflavone (I-C-9)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride Pyrrolidine-1-formyl chloride substitutes, and obtains white powder solid, yield 60.5%, HR-TOFMS (+Q)
m/z: 465.1656 ([C
25h
24n
2o
7+ H]
+calculated value: 465.1662).
embodiment 10
7,4 '-two [
n-(4-benzyl) piperidine formyl oxygen base] preparation of-5-hydroxy-isoflavone (I-C-10)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride is used
n-(4-benzyl) piperidine formyl chlorine substitutes, and obtains white powder solid, yield 73.0%, HR-TOFMS (+Q)
m/z: 673.2916 ([C
41h
40n
2o
7+ H]
+calculated value: 673.2914).
embodiment 11
7,4 '-two [
n-(4-benzyl) homopiperazine methanoyl] preparation of-5-hydroxy-isoflavone (I-C-11)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride 4-benzyl homopiperazine-1-formyl chloride hydrochloride substitutes, and obtains white powder solid, yield 75.6%, HR-TOFMS (+Q)
m/z: 703.3140 ([C
41h
42n
4o
7+ H]
+calculated value: 703.3132).
embodiment 12
7,4 '-two [
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl] preparation of-5-hydroxy-isoflavone (I-C-12)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride 4-(2-methoxyl group) benzyl diethylenediamine-1-formyl chloride hydrochloride substitutes, and obtains white powder solid, yield 63.8%, HR-TOFMS (+Q)
m/z: 735.3028 ([C
41h
42n
4o
9+ H]
+calculated value: 735.3030).
embodiment 13
7,4 '-two [
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl] preparation of-5-hydroxy-isoflavone (I-C-13)
Operating process, with embodiment 1, just will
n,N-dimethylcarbamyl chloride 4-(2-trifluoromethoxy) benzyl diethylenediamine-1-formyl chloride hydrochloride substitutes, and obtains white powder solid, yield 70.5%, HR-TOFMS (+Q)
m/z: 843.2452 ([C
41h
36f
6n
4o
9+ H]
+calculated value: 843.2465).
embodiment 14
7,4 '-two (
n-propylamine methanoyl) preparation of-5-hydroxy-isoflavone (I-C-14)
Genistein (2.0 mmol), triethylamine (6.0 mmol) and tetrahydrofuran (THF) (20 ml) is added in reaction flask, add propylisocyanate (5.0 mmol) after stirring, 40 ~ 50 DEG C of insulated and stirred are reacted 6 hours (reaction process TLC monitors); After reaction terminates, remove solvent under reduced pressure, gained crude product, through column chromatography purification (elutriant: methylene dichloride/acetone=30:1v/v), obtains white powder solid, yield 76.0%, HR-TOFMS (+Q)
m/z: 441.1666 ([C
23h
24n
2o
7+ H]
+calculated value: 441.1662).
embodiment 15
7,4 '-two (
n-benzylamine methanoyl) preparation of-5-hydroxy-isoflavone (I-C-15)
Propylisocyanate benzyl isocyanate ester, with embodiment 14, just substitutes, obtains target compound, yield 72.6%, HR-TOFMS (+Q) by operating process
m/z: 537.1657 ([C
31h
24n
2o
7+ H]
+calculated value: 537.1662).
embodiment 16
7,4 '-two [
n-(ethyl acetate) methanoyl] preparation of-5-hydroxy-isoflavone (I-C-16)
Propylisocyanate 2-isocyanic acid ethyl acetate, with embodiment 14, just substitutes, obtains target compound, yield 70.0%, HR-TOFMS (+Q) by operating process
m/z: 529.1466 ([C
25h
24n
2o
11+ H]
+calculated value: 529.1458).
embodiment 17
Adopt the synthetic method that embodiment 1 ~ 16 is similar, just genistein is used soybean isoflavones respectively, 7-methoxyl group-5, 4 '-dihydroxy isoflavone, 4 '-methoxyl group-5, 7-dihydroxy isoflavone, 7-methoxyl group-4 '-hydroxy-isoflavone, 4 '-methoxyl group-7-hydroxyisoflavone is replaced, corresponding soybean isoflavones carbamate derivates can be obtained, 7-methylates genistein carbamate derivates, 4 '-methylate genistein carbamate derivates, 7-methylated soy isoflavones carbamate derivates or 4 '-methylated soy isoflavones carbamate derivates, its chemical structure warp
1hNMR and HR-TOFMS confirms, synthesized compound is as follows:
7,4 '-two (
n, N-formyl oxygen dimethylamino)-isoflavones (I-F-1)
Yield 77.0%, HR-TOFMS (+Q)
m/z: 397.1396 ([C
21h
20n
2o
6+ H]
+calculated value: 397.1400);
7,4 '-two (
n-methyl-
n-ethylcarbamoyl oxygen base)-isoflavones (I-F-2)
Yield 70.0%, HR-TOFMS (+Q)
m/z: 425.1710 ([C
23h
24n
2o
6+ H]
+calculated value: 425.1707);
7,4 '-two (
n, N-diethylin methanoyl)-isoflavones (I-F-3)
Yield 80.5%, HR-TOFMS (+Q)
m/z: 453.2026 ([C
25h
28n
2o
6+ H]
+calculated value: 453.2020);
7,4 '-two (
n, N-diisopropylaminoethyl methanoyl)-isoflavones (I-F-4)
Yield 58.6%, HR-TOFMS (+Q)
m/z: 509.2645 ([C
29h
36n
2o
6+ H]
+calculated value: 509.2646);
7,4 '-two (piperidines-1-methanoyl)-isoflavones (I-F-5)
Yield 69.5%, HR-TOFMS (+Q)
m/z: 477.2012 ([C
27h
28n
2o
6+ H]
+calculated value: 477.2020);
7,4 '-two (
n-morpholine methanoyl)-5-hydroxy-isoflavone (I-F-6)
Yield 73.0%, HR-TOFMS (+Q)
m/z: 481.1598 ([C
25h
24n
2o
8+ H]
+calculated value: 481.1605);
7,4 '-two [
n-(4-methyl) piperazine methanoyl]-isoflavones (I-F-7)
Yield 50.5%, HR-TOFMS (+Q)
m/z: 507.2244 ([C
27h
30n
4o
6+ H]
+calculated value: 507.2238);
7,4 '-two [
n-(4-benzyl) piperazine methanoyl]-isoflavones (I-F-8)
Yield 73.2%, HR-TOFMS (+Q)
m/z: 659.2862 ([C
39h
38n
4o
6+ H]
+calculated value: 659.2864);
7,4 '-two (
n-Pyrrolidine methanoyl)-isoflavones (I-F-9)
Yield 63.5%, HR-TOFMS (+Q)
m/z: 449.1708 ([C
25h
24n
2o
6+ H]
+calculated value: 449.1707);
7,4 '-two [
n-(4-benzyl) piperidine formyl oxygen base]-isoflavones (I-F-10)
Yield 86.0%, HR-TOFMS (+Q)
m/z: 657.2966 ([C
41h
40n
2o
6+ H]
+calculated value: 657.2959);
7,4 '-two [
n-(4-benzyl) homopiperazine methanoyl]-isoflavones (I-F-11)
Yield 78.8%, HR-TOFMS (+Q)
m/z: 687.3170 ([C
41h
42n
4o
6+ H]
+calculated value: 687.3177);
7,4 '-two [
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-isoflavones (I-F-12)
Yield 60.5%, HR-TOFMS (+Q)
m/z: 719.3072 ([C
41h
42n
4o
8+ H]
+calculated value: 719.3075);
7,4 '-two [
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-isoflavones (I-F-13)
Yield 67.0%, HR-TOFMS (+Q)
m/z: 827.2500 ([C
41h
36f
6n
4o
8+ H]
+calculated value: 827.2510);
7,4 '-two (
n-propylamine methanoyl)-isoflavones (I-F-14)
Yield 72.0%, HR-TOFMS (+Q)
m/z: 425.1709 ([C
23h
24n
2o
6+ H]
+calculated value: 425.1707);
7,4 '-two (
n-benzylamine methanoyl)-isoflavones (I-F-15)
Yield 75.5%, HR-TOFMS (+Q)
m/z: 521.1704 ([C
31h
24n
2o
6+ H]
+calculated value: 521.1707);
7,4 '-two [
n-(ethyl acetate) methanoyl]-isoflavones (I-F-16)
Yield 63.9%, HR-TOFMS (+Q)
m/z: 513.1509 ([C
25h
24n
2o
10+ H]
+calculated value: 513.1504);
7-methoxyl group-4 '-(
n, N-formyl oxygen dimethylamino)-5-hydroxyl-isoflavones (I-A-1)
Yield 85.0%, HR-TOFMS (+Q)
m/z: 356.1136 ([C
19h
17nO
6+ H]
+calculated value: 356.1134);
4 '-methoxyl group-7-(
n, N-formyl oxygen dimethylamino)-5-hydroxyl-isoflavones (I-B-1)
Yield 83.6%, HR-TOFMS (+Q)
m/z: 356.1130 ([C
19h
17nO
6+ H]
+calculated value: 356.1134);
7-methoxyl group-4 '-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5-hydroxyl-isoflavones (I-A-2)
Yield 92.3%, HR-TOFMS (+Q)
m/z: 370.1285 ([C
20h
19nO
6+ H]
+calculated value: 370.1291);
4 '-methoxyl group-7-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5-hydroxyl-isoflavones (I-B-2)
Yield 85.5%, HR-TOFMS (+Q)
m/z: 370.1288 ([C
20h
19nO
6+ H]
+calculated value: 370.1291);
7-methoxyl group-4 '-(
n, N-diethylin methanoyl)-5-hydroxyl-isoflavones (I-A-3)
Yield 88.5%, HR-TOFMS (+Q)
m/z: 384.1448 ([C
21h
21nO
6+ H]
+calculated value: 384.1447);
4 '-methoxyl group-7-(
n, N-diethylin methanoyl)-5-hydroxyl-isoflavones (I-B-3)
Yield 83.0%, HR-TOFMS (+Q)
m/z: 384.1443 ([C
21h
21nO
6+ H]
+calculated value: 384.1447);
7-methoxyl group-4 '-(
n, N-diisopropylaminoethyl methanoyl)-5-hydroxyl-isoflavones (I-A-4)
Yield 76.8%, HR-TOFMS (+Q)
m/z: 412.1770 ([C
23h
25nO
6+ H]
+calculated value: 412.1760).
'-methoxyl group-7-(
n, N-diisopropylaminoethyl methanoyl)-5-hydroxyl-isoflavones (I-B-4)
Yield 80.5%, HR-TOFMS (+Q)
m/z: 412.1758 ([C
23h
25nO
6+ H]
+calculated value: 412.1760);
7-methoxyl group-4 '-(piperidines-1-methanoyl)-5-hydroxyl-isoflavones (I-A-5)
Yield 70.5%, HR-TOFMS (+Q)
m/z: 396.1440 ([C
22h
21nO
6+ H]
+calculated value: 396.1447);
4 '-methoxyl group-7-(piperidines-1-methanoyl)-5-hydroxyl-isoflavones (I-B-5)
Yield 67.9%, HR-TOFMS (+Q)
m/z: 396.1446 ([C
22h
21nO
6+ H]
+calculated value: 396.1447);
7-methoxyl group-4 '-(
n-morpholine methanoyl)-5-hydroxyl-isoflavones (I-A-6)
Yield 65.0%, HR-TOFMS (+Q)
m/z: 398.1246 ([C
21h
19nO
7+ H]
+calculated value: 398.1240);
4 '-methoxyl group-7-(
n-morpholine methanoyl)-5-hydroxyl-isoflavones (I-B-6)
Yield 67.0%, HR-TOFMS (+Q)
m/z: 398.1234 ([C
21h
19nO
7+ H]
+calculated value: 398.1240);
7-methoxyl group-4 '-[
n-(4-methyl) piperazine methanoyl]-5-hydroxyl-isoflavones (I-A-7)
Yield 74.8%, HR-TOFMS (+Q)
m/z: 411.1550 ([C
22h
22n
2o
6+ H]
+calculated value: 411.1556);
4 '-methoxyl group-7-[
n-(4-methyl) piperazine methanoyl]-5-hydroxyl-isoflavones (I-B-7)
Yield 73.5%, HR-TOFMS (+Q)
m/z: 411.1554 ([C
22h
22n
2o
6+ H]
+calculated value: 411.1556);
7-methoxyl group-4 '-[
n-(4-benzyl) piperazine methanoyl]-5-hydroxyl-isoflavones (I-A-8)
Yield 83.0%, HR-TOFMS (+Q)
m/z: 487.1874 ([C
28h
26n
2o
6+ H]
+calculated value: 487.1869);
4 '-methoxyl group-7-[
n-(4-benzyl) piperazine methanoyl]-5-hydroxyl-isoflavones (I-B-8)
Yield 78.8%, HR-TOFMS (+Q)
m/z: 487.1863 ([C
28h
26n
2o
6+ H]
+calculated value: 487.1869);
7-methoxyl group-4 '-(
n-Pyrrolidine methanoyl)-5-hydroxyl-isoflavones (I-A-9)
Yield 60.0%, HR-TOFMS (+Q)
m/z: 382.1289 ([C
21h
19nO
6+ H]
+calculated value: 382.1291);
4 '-methoxyl group-7-(
n-Pyrrolidine methanoyl)-5-hydroxyl-isoflavones (I-B-9)
Yield 66.0%, HR-TOFMS (+Q)
m/z: 382.1280 ([C
21h
19nO
6+ H]
+calculated value: 382.1291);
7-methoxyl group-4 '-[
n-(4-benzyl) piperidine formyl oxygen base]-5-hydroxyl-isoflavones (I-A-10)
Yield 70.0%, HR-TOFMS (+Q)
m/z: 486.1908 ([C
29h
27nO
6+ H]
+calculated value: 486.1917);
4 '-methoxyl group-7-[
n-(4-benzyl) piperidine formyl oxygen base]-5-hydroxyl-isoflavones (I-B-10)
Yield 73.0%, HR-TOFMS (+Q)
m/z: 486.1912 ([C
29h
27nO
6+ H]
+calculated value: 486.1917);
7-methoxyl group-4 '-[
n-(4-benzyl) homopiperazine methanoyl]-5-hydroxyl-isoflavones (I-A-11)
Yield 60.8%, HR-TOFMS (+Q)
m/z: 501.2030 ([C
29h
28n
2o
6+ H]
+calculated value: 501.2026);
4 '-methoxyl group-7-[
n-(4-benzyl) homopiperazine methanoyl]-5-hydroxyl-isoflavones (I-B-11)
Yield 59.5%, HR-TOFMS (+Q)
m/z: 501.2025 ([C
29h
28n
2o
6+ H]
+calculated value: 501.2026);
7-methoxyl group-4 '-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones (I-A-12)
Yield 76.5%, HR-TOFMS (+Q)
m/z: 517.1968 ([C
29h
28n
2o
7+ H]
+calculated value: 517.1975);
4 '-methoxyl group-7-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones (I-B-12)
Yield 70.5%, HR-TOFMS (+Q)
m/z: 517.1966 ([C
29h
28n
2o
7+ H]
+calculated value: 517.1975);
7-methoxyl group-4 '-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones (I-A-13)
Yield 67.0%, HR-TOFMS (+Q)
m/z: 571.1690 ([C
29h
25f
3n
2o
7+ H]
+calculated value: 571.1692);
4 '-methoxyl group-7-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones (I-B-13)
Yield 70.0%, HR-TOFMS (+Q)
m/z: 571.1682 ([C
29h
25f
3n
2o
7+ H]
+calculated value: 571.1692);
7-methoxyl group-4 '-(
n-propylamine methanoyl)-5-hydroxyl-isoflavones (I-A-14)
Yield 56.8%, HR-TOFMS (+Q)
m/z: 370.1287 ([C
20h
19nO
6+ H]
+calculated value: 370.1291);
4 '-methoxyl group-7-(
n-propylamine methanoyl)-5-hydroxyl-isoflavones (I-B-14)
Yield 61.5%, HR-TOFMS (+Q)
m/z: 370.1285 ([C
20h
19nO
6+ H]
+calculated value: 370.1291);
7-methoxyl group-4 '-(
n-benzylamine methanoyl)-5-hydroxyl-isoflavones (I-A-15)
Yield 65.0%, HR-TOFMS (+Q)
m/z: 418.1289 ([C
24h
19nO
6+ H]
+calculated value: 418.1291);
4 '-methoxyl group-7-(
n-benzylamine methanoyl)-5-hydroxyl-isoflavones (I-B-15)
Yield 62.0%, HR-TOFMS (+Q)
m/z: 418.1282 ([C
24h
19nO
6+ H]
+calculated value: 418.1291);
7-methoxyl group-4 '-[
n-(ethyl acetate) methanoyl]-5-hydroxyl-isoflavones (I-A-16)
Yield 58.0%, HR-TOFMS (+Q)
m/z: 414.1185 ([C
21h
19nO
8+ H]
+calculated value: 414.1189);
4 '-methoxyl group-7-[
n-(ethyl acetate) methanoyl]-5-hydroxyl-isoflavones (I-B-16)
Yield 53.0%, HR-TOFMS (+Q)
m/z: 414.1180 ([C
21h
19nO
8+ H]
+calculated value: 414.1189);
7-methoxyl group-4 '-(
n, N-formyl oxygen dimethylamino)-isoflavones (I-D-1)
Yield 91.5%, HR-TOFMS (+Q)
m/z: 340.1176 ([C
19h
17nO
5+ H]
+calculated value: 340.1179);
4 '-methoxyl group-7-(
n, N-formyl oxygen dimethylamino)-isoflavones (I-E-1)
Yield 86.0%, HR-TOFMS (+Q)
m/z: 340.1182 ([C
19h
17nO
5+ H]
+calculated value: 340.1179);
7-methoxyl group-4 '-(
n-methyl-
n-ethylcarbamoyl oxygen base)-isoflavones (I-D-2)
Yield 90.0%, HR-TOFMS (+Q)
m/z: 354.1340 ([C
20h
19nO
5+ H]
+calculated value: 354.1336);
4 '-methoxyl group-7-(
n-methyl-
n-ethylcarbamoyl oxygen base)-isoflavones (I-E-2)
Yield 91.8%, HR-TOFMS (+Q)
m/z: 354.1335 ([C
20h
19nO
5+ H]
+calculated value: 354.1336);
7-methoxyl group-4 '-(
n, N-diethylin methanoyl)-isoflavones (I-D-3)
Yield 87.5%, HR-TOFMS (+Q)
m/z: 368.1490 ([C
21h
21nO
5+ H]
+calculated value: 368.1492);
4 '-methoxyl group-7-(
n, N-diethylin methanoyl)-isoflavones (I-E-3)
Yield 93.6%, HR-TOFMS (+Q)
m/z: 368.1498 ([C
21h
21nO
5+ H]
+calculated value: 368.1492).
methoxyl group-4 '-(
n, N-diisopropylaminoethyl methanoyl)-isoflavones (I-D-4)
Yield 80.0%, HR-TOFMS (+Q)
m/z: 396.1801 ([C
23h
25nO
5+ H]
+calculated value: 396.1805);
4 '-methoxyl group-7-(
n, N-diisopropylaminoethyl methanoyl)-isoflavones (I-E-4)
Yield 78.5%, HR-TOFMS (+Q)
m/z: 396.1800 ([C
23h
25nO
5+ H]
+calculated value: 396.1805);
7-methoxyl group-4 '-(piperidines-1-methanoyl)-isoflavones (I-D-5)
Yield 68.0%, HR-TOFMS (+Q)
m/z: 380.1483 ([C
22h
21nO
5+ H]
+calculated value: 380.1492);
4 '-methoxyl group-7-(piperidines-1-methanoyl)-isoflavones (I-E-5)
Yield 69.5%, HR-TOFMS (+Q)
m/z: 380.1486 ([C
22h
21nO
5+ H]
+calculated value: 380.1492);
7-methoxyl group-4 '-(
n-morpholine methanoyl)-isoflavones (I-D-6)
Yield 60.0%, HR-TOFMS (+Q)
m/z: 382.1288 ([C
21h
19nO
6+ H]
+calculated value: 382.1285);
4 '-methoxyl group-7-(
n-morpholine methanoyl)-isoflavones (I-E-6)
Yield 66.0%, HR-TOFMS (+Q)
m/z: 382.1280 ([C
21h
19nO
6+ H]
+calculated value: 382.1285);
7-methoxyl group-4 '-[
n-(4-methyl) piperazine methanoyl]-isoflavones (I-D-7)
Yield 80.5%, HR-TOFMS (+Q)
m/z: 395.1595 ([C
22h
22n
2o
5+ H]
+calculated value: 395.1601);
4 '-methoxyl group-7-[
n-(4-methyl) piperazine methanoyl]-isoflavones (I-E-7)
Yield 76.0%, HR-TOFMS (+Q)
m/z: 395.1592 ([C
22h
22n
2o
5+ H]
+calculated value: 395.1601);
7-methoxyl group-4 '-[
n-(4-benzyl) piperazine methanoyl]-isoflavones (I-D-8)
Yield 86.0%, HR-TOFMS (+Q)
m/z: 471.1920 ([C
28h
26n
2o
5+ H]
+calculated value: 471.1914);
4 '-methoxyl group-7-[
n-(4-benzyl) piperazine methanoyl]-isoflavones (I-E-8)
Yield 82.8%, HR-TOFMS (+Q)
m/z: 471.1912 ([C
28h
26n
2o
5+ H]
+calculated value: 471.1914);
7-methoxyl group-4 '-(
n-Pyrrolidine methanoyl)-isoflavones (I-D-9)
Yield 62.0%, HR-TOFMS (+Q)
m/z: 366.1335 ([C
21h
19nO
5+ H]
+calculated value: 366.1336);
4 '-methoxyl group-7-(
n-Pyrrolidine methanoyl)-isoflavones (I-E-9)
Yield 68.0%, HR-TOFMS (+Q)
m/z: 366.1330 ([C
21h
19nO
5+ H]
+calculated value: 366.1336);
7-methoxyl group-4 '-[
n-(4-benzyl) piperidine formyl oxygen base]-isoflavones (I-D-10)
Yield 73.0%, HR-TOFMS (+Q)
m/z: 470.1966 ([C
29h
27nO
5+ H]
+calculated value: 470.1962);
4 '-methoxyl group-7-[
n-(4-benzyl) piperidine formyl oxygen base]-isoflavones (I-E-10)
Yield 70.0%, HR-TOFMS (+Q)
m/z: 470.1956 ([C
29h
27nO
5+ H]
+calculated value: 470.1962);
7-methoxyl group-4 '-[
n-(4-benzyl) homopiperazine methanoyl]-isoflavones (I-D-11)
Yield 57.5%, HR-TOFMS (+Q)
m/z: 485.2060 ([C
29h
28n
2o
5+ H]
+calculated value: 485.2071);
4 '-methoxyl group-7-[
n-(4-benzyl) homopiperazine methanoyl]-isoflavones (I-E-11)
Yield 52.0%, HR-TOFMS (+Q)
m/z: 485.2065 ([C
29h
28n
2o
5+ H]
+calculated value: 485.2071);
7-methoxyl group-4 '-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-isoflavones (I-D-12)
Yield 78.3%, HR-TOFMS (+Q)
m/z: 501.2018 ([C
29h
28n
2o
6+ H]
+calculated value: 501.2020);
4 '-methoxyl group-7-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-isoflavones (I-E-12)
Yield 80.7%, HR-TOFMS (+Q)
m/z: 501.2010 ([C
29h
28n
2o
6+ H]
+calculated value: 501.2020);
7-methoxyl group-4 '-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-isoflavones (I-D-13)
Yield 69.0%, HR-TOFMS (+Q)
m/z: 555.1730 ([C
29h
25f
3n
2o
6+ H]
+calculated value: 555.1737);
4 '-methoxyl group-7-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-isoflavones (I-E-13)
Yield 66.0%, HR-TOFMS (+Q)
m/z: 555.1736 ([C
29h
25f
3n
2o
6+ H]
+calculated value: 555.1737);
7-methoxyl group-4 '-(
n-propylamine methanoyl)-isoflavones (I-D-14)
Yield 50.0%, HR-TOFMS (+Q)
m/z: 354.1336 ([C
20h
19nO
5+ H]
+calculated value: 354.1336);
4 '-methoxyl group-7-(
n-propylamine methanoyl)-isoflavones (I-E-14)
Yield 54.5%, HR-TOFMS (+Q)
m/z: 354.1332 ([C
20h
19nO
5+ H]
+calculated value: 354.1336);
7-methoxyl group-4 '-(
n-benzylamine methanoyl)-isoflavones (I-D-15)
Yield 67.5%, HR-TOFMS (+Q)
m/z: 402.1339 ([C
24h
19nO
5+ H]
+calculated value: 402.1336);
4 '-methoxyl group-7-(
n-benzylamine methanoyl)-isoflavones (I-E-15)
Yield 61.0%, HR-TOFMS (+Q)
m/z: 402.1345 ([C
24h
19nO
5+ H]
+calculated value: 402.1336);
7-methoxyl group-4 '-[
n-(ethyl acetate) methanoyl]-isoflavones (I-D-16)
Yield 64.5%, HR-TOFMS (+Q)
m/z: 398.1230 ([C
21h
19nO
7+ H]
+calculated value: 398.1234);
4 '-methoxyl group-7-[
n-(ethyl acetate) methanoyl]-isoflavones (I-E-16)
Yield 59.0%, HR-TOFMS (+Q)
m/z: 398.1227 ([C
21h
19nO
7+ H]
+calculated value: 398.1234).
embodiment 18
7-(
n, N-formyl oxygen dimethylamino)-5,4 '-dihydroxyl-isoflavones (I-A-17) and 4 '-(
n, N-formyl oxygen dimethylamino) preparation of-5,7-dihydroxyl-isoflavones (I-B-17)
Genistein (2.0 mmol), KOH(2.0 mmol is added in reaction flask) and
n,N-dimethyl formamide (20 ml), adds after stirring
n,N-dimethylcarbamyl chloride (2.0 mmol), stirring at room temperature is reacted 12 hours (reaction process TLC follows the tracks of); After reaction terminates, by reaction solution impouring deionized water, with 10%HCl aqueous solution regulator solution pH to acid, the off-white color solid that suction filtration is separated out, through purification by silica gel column chromatography (elutriant: methylene dichloride/acetone=30:1v/v), respectively 7-(
n, N-formyl oxygen dimethylamino)-5,4 '-dihydroxyl-isoflavones, yield 45.0%, mp:>260 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.93 (s, 1H, 5-OH), 9.65 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.41 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 6.97 (d,
j=1.6Hz, 1H, 6-H), 6.84 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.65 (d,
j=1.6Hz, 1H, 8-H), 3.05 (s, 3H, NCH
3), 2.93 (s, 3H, NCH
3), HR-TOFMS (+Q)
m/z: 342.0972 ([C
18h
15nO
6+ H]
+calculated value: 342.0978); And 4 '-(
n, N-formyl oxygen dimethylamino)-5,7-dihydroxyl-isoflavones, yield 12.0%, mp:238 ~ 239 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.88 (s, 1H, 5-OH), 10.96 (s, 1H, 7-OH), 8.46 (s, 1H, 2-H), 7.57 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.19 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.42 (d,
j=2.0Hz, 1H, 6-H), 6.25 (d,
j=2.0Hz, 1H, 8-H), 3.06 (s, 3H, NCH
3), 2.93 (s, 3H, NCH
3), HR-TOFMS (+Q)
m/z: 342.0976 ([C
18h
15nO
6+ H]
+calculated value: 342.0978).
embodiment 19
Adopt synthetic method as similar in embodiment 18, just will
n,Nthe corresponding acyl chlorides of-dimethylcarbamyl chloride is replaced, and genistein soybean isoflavones is replaced, and can obtain mono-substituted genistein carbamate derivates and mono-substituted soybean isoflavones carbamate derivates, its chemical structure warp
1hNMR and HR-TOFMS confirms; Synthesized compound is as follows:
7-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5,4 '-dihydroxyl-isoflavones (I-A-18)
Yield 40.0%, mp:230 ~ 232 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.93 (s, 1H, 5-OH), 9.66 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.41 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 6.97 (d,
j=2.0Hz, 1H, 6-H), 6.84 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.65 (d,
j=2.0Hz, 1H, 8-H), 3.30 ~ 3.45 (m, 2H, NCH
2), 3.03 (s, 1/2NCH
3), 2.92 (s, 1/2NCH
3), 1.10 ~ 1.20 (m, 3H, CH
3), HR-TOFMS (+Q)
m/z: 356.1126 ([C
19h
17nO
6+ H]
+calculated value: 356.1134);
4 '-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5,7-dihydroxyl-isoflavones (I-B-18)
Yield 20.0%, mp:183 ~ 185 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.87 (s, 1H, 5-OH), 10.95 (s, 1H, 7-OH), 8.45 (s, 1H, 2-H), 7.57 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.19 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.42 (d,
j=2.0Hz, 1H, 6-H), 6.25 (d,
j=2.0Hz, 1H, 8-H), 3.30 ~ 3.45 (m, 2H, NCH
2), 3.04 (s, 1/2NCH
3), 2.91 (s, 1/2NCH
3), 1.09 ~ 1.21 (m, 3H, CH
3), HR-TOFMS (+Q)
m/z: 356.1137 ([C
19h
17nO
6+ H]
+calculated value: 356.1134);
7-(
n, N-diethylin methanoyl)-5,4 '-dihydroxyl-isoflavones (I-A-19)
Yield 49.0%, mp:196 ~ 198 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.93 (s, 1H, 5-OH), 9.65 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.41 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 6.97 (d,
j=2.0Hz, 1H, 6-H), 6.84 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.65 (d,
j=2.0Hz, 1H, 8-H), 3.41 (q,
j=6.8Hz, 2H, NCH
2), 3.32 (q,
j=6.8Hz, 2H, NCH
2), 1.20 (t,
j=6.8Hz, 3H, CH
3), 1.11 ~ 1.15 (t,
j=6.8Hz, 3H, CH
3), HR-TOFMS (+Q)
m/z: 370.1296 ([C
20h
19nO
6+ H]
+calculated value: 370.1291);
4 '-(
n, N-diethylin methanoyl)-5,7-dihydroxyl-isoflavones (I-B-19)
Yield 15.5%, mp:182 ~ 184 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.87 (s, 1H, 5-OH), 10.95 (s, 1H, 7-OH), 8.45 (s, 1H, 2-H), 7.57 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.19 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.42 (d,
j=2.0Hz, 1H, 6-H), 6.25 (d,
j=2.0Hz, 1H, 8-H), 3.40 (q,
j=6.8Hz, 2H, NCH
2), 3.33 (q,
j=6.8Hz, 2H, NCH
2), 1.21 (t,
j=6.8Hz, 3H, CH
3), 1.12 (t,
j=6.8Hz, 3H, CH
3), HR-TOFMS (+Q)
m/z: 370.1288 ([C
20h
19nO
6+ H]
+calculated value: 370.1291);
7-(
n, N-diisopropylaminoethyl methanoyl)-5,4 '-dihydroxyl-isoflavones (I-A-20)
Yield 41.0%, mp:224 ~ 225 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.94 (s, 1H, 5-OH), 9.65 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.41 (d,
j=8.8Hz, 2H, 2 ', 6 '-H), 6.94 (d,
j=2.0Hz, 1H, 6-H), 6.84 (d,
j=8.8Hz, 2H, 3 ', 5 '-H), 6.62 (d,
j=2.0Hz, 1H, 8-H), 4.00 (brs, 2H, 2 × NCH), 1.26 (brs, 12H, 4 × CH
3), HR-TOFMS (+Q)
m/z: 398.1596 ([C
22h
23nO
6+ H]
+calculated value: 398.1604);
4 '-(
n, N-diisopropylaminoethyl methanoyl)-5,7-dihydroxyl-isoflavones (I-B-20)
Yield 18.5%, mp:230 ~ 231 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.88 (s, 1H, 5-OH), 10.95 (s, 1H, 7-OH), 8.45 (s, 1H, 2-H), 7.57 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.17 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.42 (d,
j=2.0Hz, 1H, 6-H), 6.25 (d,
j=2.0Hz, 1H, 8-H), 4.00 (brs, 2H, 2 × NCH), 1.27 (brs, 12H, 4 × CH
3), HR-TOFMS (+Q)
m/z: 398.1597 ([C
22h
23nO
6+ H]
+calculated value: 398.1604);
7-(piperidines-1-methanoyl)-5,4 '-dihydroxyl-isoflavones (I-A-21)
Yield 48.0%, mp:232 ~ 233 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.93 (s, 1H, 5-OH), 9.65 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.41 (d
j=8.4Hz, 2H, 2 ', 6 '-H), 6.97 (d,
j=2.0Hz, 1H, 6-H), 6.84 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.66 (d,
j=2.0Hz, 1H, 8-H), 3.55 (s, 2H, NCH
2), 3.42 (s, 2H, NCH
2), 1.59 (brs, 6H, 3 × CH
2), HR-TOFMS (+Q)
m/z: 382.1288 ([C
21h
19nO
6+ H]
+calculated value: 382.1291);
4 '-(piperidines-1-methanoyl)-5,7-dihydroxyl-isoflavones (I-B-21)
Yield 20.0%, mp:216 ~ 217 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.87 (s, 1H, 5-OH), 10.95 (s, 1H, 7-OH), 8.46 (s, 1H, 2-H), 7.57 (d,
j=8.8Hz, 2H, 2 ', 6 '-H), 7.18 (d,
j=8.8Hz, 2H, 3 ', 5 '-H), 6.42 (d,
j=2.0Hz, 1H, 6-H), 6.25 (d,
j=2.0Hz, 1H, 8-H), 3.56 (brs, 2H, NCH
2), 3.41 (brs, 2H, NCH
2), 1.56 ~ 1.59 (m, 6H, 3 × CH
2), HR-TOFMS (+Q)
m/z: 382.1283 ([C
21h
19nO
6+ H]
+calculated value: 382.1291);
7-(
n-morpholine methanoyl)-5,4 '-dihydroxyl-isoflavones (I-A-22)
Yield 51.0%, mp:221 ~ 223 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.94 (s, 1H, 5-OH), 9.65 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.41 (d
j=8.4Hz, 2H, 2 ', 6 '-H), 7.01 (d,
j=2.0Hz, 1H, 6-H), 6.84 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.70 (d,
j=2.0Hz, 1H, 8-H), 3.65 ~ 3.67 (m, 4H, 2 × OCH
2), 3.59 (brs, 2H, NCH
2), 3.44 (brs, 2H, NCH
2), HR-TOFMS (+Q)
m/z: 384.1078 ([C
20h
17nO
7+ H]
+calculated value: 384.1083);
4 '-(
n-morpholine methanoyl)-5,7-dihydroxyl-isoflavones (I-B-22)
Yield 14.8%, mp:243 ~ 244 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.87 (s, 1H, 5-OH), 10.96 (s, 1H, 7-OH), 8.46 (s, 1H, 2-H), 7.58 (d,
j=8.8Hz, 2H, 2 ', 6 '-H), 7.21 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.42 (d,
j=2.0Hz, 1H, 6-H), 6.25 (d,
j=2.0Hz, 1H, 8-H), 3.60 ~ 3.66 (m, 4H, 2 × OCH
2), 3.43 (brs, 2H, NCH
2), 3.35 (brs, 2H, NCH
2), HR-TOFMS (+Q)
m/z: 384.1081 ([C
20h
17nO
7+ H]
+calculated value: 384.1083);
7-[
n-(4-methyl) piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones (I-A-23)
Yield 47.8%, mp:207 ~ 209 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.93 (s, 1H, 5-OH), 9.65 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.40 (d
j=8.4Hz, 2H, 2 ', 6 '-H), 6.99 (d,
j=1.6Hz, 1H, 6-H), 6.84 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.67 (d,
j=1.6Hz, 1H, 8-H), 3.59 (brs, 2H, NCH
2), 3.45 (brs, 2H, NCH
2), 2.40 (brs, 4H, 2 × NCH2), 2.25 (s, 3H, NCH
3), HR-TOFMS (+Q)
m/z: 397.1398 ([C
21h
20n
2o
6+ H]
+calculated value: 397.1400);
4 '-[
n-(4-methyl) piperazine methanoyl]-5,7-dihydroxyl-isoflavones hydrochloride (I-B-23)
Yield 17.2%, mp:>260 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.85 (s, 1H, 5-OH), 11.10 (brs, 1H, HCl), 11.06 (s, 1H, 7-OH), 8.47 (s, 1H, 2-H), 7.60 (d,
j=8.4Hz, 2H, 2 ', 6 '-H), 7.24 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.45 (d,
j=2.0Hz, 1H, 6-H), 6.27 (d,
j=2.0Hz, 1H, 8-H), 4.13 ~ 4.28 (m, 2H, NCH
2), 3.14 ~ 3.44 (m, 6H, 3 × NCH
2), 2.80 (s, 3H, NCH
3), HR-TOFMS (+Q)
m/z: 397.1406 ([C
21h
20n
2o
6+ H]
+calculated value: 397.1400);
7-[
n-(4-benzyl) piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones (I-A-24)
Yield 43.1%, mp:178 ~ 180 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.93 (s, 1H, 5-OH), 9.65 (s, 1H, 4 '-OH), 8.50 (s, 1H, 2-H), 7.40 (d
j=8.4Hz, 2H, 2 ', 6 '-H), 7.27 ~ 7.37 (m, 5H, Ar-H), 6.98 (d,
j=1.6Hz, 1H, 6-H), 6.84 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.67 (d,
j=1.6Hz, 1H, 8-H), 3.59 (brs, 2H, NCH
2), 3.53 (s, 2H, NCH
2), 3.45 (brs, 2H, NCH
2), 2.44 (brs, 4H, 2 × NCH
2), HR-TOFMS (+Q)
m/z: 473.1720 ([C
27h
24n
2o
6+ H]
+calculated value: 473.1713);
4 '-[
n-(4-benzyl) piperazine methanoyl]-5,7-dihydroxyl-isoflavones hydrochloride (I-B-24)
Yield 18.2%, mp:>260 DEG C,
1h-NMR (400MHz, DMSO-d
6)
δ: 12.85 (s, 1H, 5-OH), 11.39 (s, 1H, HCl), 11.05 (s, 1H, 7-OH), 8.47 (s, 1H, 2-H), 7.63 ~ 7.64 (m, 2H, Ar-H), 7.60 (d
j=8.4Hz, 2H, 2 ', 6 '-H), 7.47 ~ 7.49 (m, 3H, Ar-H), 7.23 (d,
j=8.4Hz, 2H, 3 ', 5 '-H), 6.45 (d,
j=2.0Hz, 1H, 6-H), 6.27 (d,
j=2.0Hz, 1H, 8-H), 4.12 ~ 4.38 (m, 4H, 2 × NCH
2), 3.35 ~ 3.60 (m, 4H, 3 × NCH
2), 3.17 (brs, 2H, NCH
2), HR-TOFMS (+Q)
m/z: 473.1715 ([C
27h
24n
2o
6+ H]
+calculated value: 473.1713);
7-(
n-Pyrrolidine methanoyl)-5,4 '-dihydroxyl-isoflavones (I-A-25)
Yield 42.9%, HR-TOFMS (+Q)
m/z: 368.1132 ([C
20h
17nO
6+ H]
+calculated value: 368.1134);
4 '-(
n-Pyrrolidine methanoyl)-5,7-dihydroxyl-isoflavones (I-B-25)
Yield 16.5%, HR-TOFMS (+Q)
m/z: 368.1126 ([C
20h
17nO
6+ H]
+calculated value: 368.1134);
7-[
n-(4-benzyl) piperidine formyl oxygen base]-5,4 '-dihydroxyl-isoflavones (I-A-26)
Yield 38.8%, HR-TOFMS (+Q)
m/z: 472.1754 ([C
28h
25nO
6+ H]
+calculated value: 472.1760);
4 '-[
n-(4-benzyl) piperidine formyl oxygen base]-5,7-dihydroxyl-isoflavones (I-B-26)
Yield 15.3%, HR-TOFMS (+Q)
m/z: 472.1750 ([C
28h
25nO
6+ H]
+calculated value: 472.1760);
7-[
n-(4-benzyl) homopiperazine methanoyl]-5,4 '-dihydroxyl-isoflavones (I-A-27)
Yield 43.0%, HR-TOFMS (+Q)
m/z: 487.1867 ([C
28h
26n
2o
6+ H]
+calculated value: 487.1869);
4 '-[
n-(4-benzyl) homopiperazine methanoyl]-5,7-dihydroxyl-isoflavones (I-B-27)
Yield 12.8%, HR-TOFMS (+Q)
m/z: 487.1863 ([C
28h
26n
2o
6+ H]
+calculated value: 487.1869);
7-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones (I-A-28)
Yield 55.0%, HR-TOFMS (+Q)
m/z: 503.1815 ([C
28h
26n
2o
7+ H]
+calculated value: 503.1818);
4 '-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5,7-dihydroxyl-isoflavones (I-B-28)
Yield 15.0%, HR-TOFMS (+Q)
m/z: 503.1822 ([C
28h
26n
2o
7+ H]
+calculated value: 503.1818);
7-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones (I-A-29)
Yield 47.0%, HR-TOFMS (+Q)
m/z: 557.1538 ([C
28h
23f
3n
2o
7+ H]
+calculated value: 557.1536);
4 '-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5,7-dihydroxyl-isoflavones (I-B-29)
Yield 20.0%, HR-TOFMS (+Q)
m/z: 557.1530 ([C
28h
23f
3n
2o
7+ H]
+calculated value: 557.1536);
7-(
n-propylamine methanoyl)-5,4 '-dihydroxyl-isoflavones (I-A-30)
Yield 43.7%, HR-TOFMS (+Q)
m/z: 356.1134 ([C
19h
17nO
6+ H]
+calculated value: 356.1134);
4 '-(
n-propylamine methanoyl)-5,7-dihydroxyl-isoflavones (I-B-30)
Yield 17.0%, HR-TOFMS (+Q)
m/z: 356.1128 ([C
19h
17nO
6+ H]
+calculated value: 356.1134);
7-(
n-benzylamine methanoyl)-5,4 '-dihydroxyl-isoflavones (I-A-31)
Yield 49.0%, HR-TOFMS (+Q)
m/z: 404.1139 ([C
23h
17nO
6+ H]
+calculated value: 404.1134);
4 '-(
n-benzylamine methanoyl)-5,7-dihydroxyl-isoflavones (I-B-31)
Yield 22.5%, HR-TOFMS (+Q)
m/z: 404.1124 ([C
23h
17nO
6+ H]
+calculated value: 404.1134);
7-[
n-(ethyl acetate) methanoyl]-5,4 '-dihydroxyl-isoflavones (I-A-32)
Yield 41.5%, HR-TOFMS (+Q)
m/z: 400.1026 ([C
20h
17nO
8+ H]
+calculated value: 400.1032);
4 '-[
n-(ethyl acetate) methanoyl]-5,7-dihydroxyl-isoflavones (I-B-32)
Yield 13.0%, HR-TOFMS (+Q)
m/z: 400.1030 ([C
20h
17nO
8+ H]
+calculated value: 400.1032).
embodiment 20
logical method prepared by amino formate compounds (I) and sour salify
Add in reaction flask amino formate compounds (
i) (R
1nR
2for piperazine ring, homopiperazine ring, 4-position are by C
1~ C
12the piperazine ring that alkyl replaces or homopiperazine ring, 4-position by benzyl or substituted benzyl the piperazine ring that replaces or homopiperazine ring) 2.0 mmol and acetone 50 ml, the acid of 6.0 mmol is added after stirring, temperature rising reflux stirring reaction 20 minutes, room temperature is cooled to after reaction terminates, filter separate out solid, obtain amino formate compounds (
i) salt, its chemical structure warp
1h NMR and ESI-MS confirms.
Claims (4)
1. a quasi-isoflavone amino formate compounds, is characterized in that this compounds is selected from: 7,4 '-two (
n, N-formyl oxygen dimethylamino)-5-hydroxy-isoflavone, 7,4 '-two (
n-methyl-
n-ethylcarbamoyl oxygen base)-5-hydroxy-isoflavone, 7,4 '-two (
n, N-diethylin methanoyl)-5-hydroxy-isoflavone, 7,4 '-two (
n, N-diisopropylaminoethyl methanoyl)-5-hydroxy-isoflavone, 7,4 '-two (piperidines-1-methanoyl)-5-hydroxy-isoflavone, 7,4 '-two (
n-morpholine methanoyl)-5-hydroxy-isoflavone, 7,4 '-two [
n-(4-methyl) piperazine methanoyl]-5-hydroxy-isoflavone, 7,4 '-two [
n-(4-benzyl) piperazine methanoyl]-5-hydroxy-isoflavone, 7,4 '-two (
n-Pyrrolidine methanoyl)-5-hydroxy-isoflavone, 7,4 '-two [
n-(4-benzyl) piperidine formyl oxygen base]-5-hydroxy-isoflavone, 7,4 '-two [
n-(4-benzyl) homopiperazine methanoyl]-5-hydroxy-isoflavone, 7,4 '-two [
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5-hydroxy-isoflavone, 7,4 '-two [
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5-hydroxy-isoflavone, 7,4 '-two (
n-propylamine methanoyl)-5-hydroxy-isoflavone, 7,4 '-two (
n-benzylamine methanoyl)-5-hydroxy-isoflavone, 7,4 '-two [
n-(ethyl acetate) methanoyl]-5-hydroxy-isoflavone, 7,4 '-two (
n-morpholine methanoyl)-5-hydroxy-isoflavone, 7-methoxyl group-4 '-(
n, N-formyl oxygen dimethylamino)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n, N-formyl oxygen dimethylamino)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(
n, N-diethylin methanoyl)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n, N-diethylin methanoyl)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(
n, N-diisopropylaminoethyl methanoyl)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n, N-diisopropylaminoethyl methanoyl)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(piperidines-1-methanoyl)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(piperidines-1-methanoyl)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(
n-morpholine methanoyl)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n-morpholine methanoyl)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-[
n-(4-methyl) piperazine methanoyl]-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-[
n-(4-methyl) piperazine methanoyl]-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-[
n-(4-benzyl) piperazine methanoyl]-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-[
n-(4-benzyl) piperazine methanoyl]-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(
n-Pyrrolidine methanoyl)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n-Pyrrolidine methanoyl)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-[
n-(4-benzyl) piperidine formyl oxygen base]-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-[
n-(4-benzyl) piperidine formyl oxygen base]-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-[
n-(4-benzyl) homopiperazine methanoyl]-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-[
n-(4-benzyl) homopiperazine methanoyl]-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(
n-propylamine methanoyl)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n-propylamine methanoyl)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-(
n-benzylamine methanoyl)-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-(
n-benzylamine methanoyl)-5-hydroxyl-isoflavones, 7-methoxyl group-4 '-[
n-(ethyl acetate) methanoyl]-5-hydroxyl-isoflavones, 4 '-methoxyl group-7-[
n-(ethyl acetate) methanoyl]-5-hydroxyl-isoflavones, 7-(
n, N-formyl oxygen dimethylamino)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n, N-formyl oxygen dimethylamino)-5,7-dihydroxyl-isoflavones, 7-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n-methyl-
n-ethylcarbamoyl oxygen base)-5,7-dihydroxyl-isoflavones, 7-(
n, N-diethylin methanoyl)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n, N-diethylin methanoyl)-5,7-dihydroxyl-isoflavones, 7-(
n, N-diisopropylaminoethyl methanoyl)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n, N-diisopropylaminoethyl methanoyl)-5,7-dihydroxyl-isoflavones, 7-(piperidines-1-methanoyl)-5,4 '-dihydroxyl-isoflavones, 4 '-(piperidines-1-methanoyl)-5,7-dihydroxyl-isoflavones, 7-(
n-morpholine methanoyl)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n-morpholine methanoyl)-5,7-dihydroxyl-isoflavones, 7-[
n-(4-methyl) piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones, 4 '-[
n-(4-methyl) piperazine methanoyl]-5,7-dihydroxyl-isoflavones hydrochloride, 7-[
n-(4-benzyl) piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones, 4 '-[
n-(4-benzyl) piperazine methanoyl]-5,7-dihydroxyl-isoflavones hydrochloride, 7-(
n-Pyrrolidine methanoyl)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n-Pyrrolidine methanoyl)-5,7-dihydroxyl-isoflavones, 7-[
n-(4-benzyl) piperidine formyl oxygen base]-5,4 '-dihydroxyl-isoflavones, 4 '-[
n-(4-benzyl) piperidine formyl oxygen base]-5,7-dihydroxyl-isoflavones, 7-[
n-(4-benzyl) homopiperazine methanoyl]-5,4 '-dihydroxyl-isoflavones, 4 '-[
n-(4-benzyl) homopiperazine methanoyl]-5,7-dihydroxyl-isoflavones, 7-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones, 4 '-[
n-[4-(2-methoxyl group) benzyl] piperazine methanoyl]-5,7-dihydroxyl-isoflavones, 7-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5,4 '-dihydroxyl-isoflavones, 4 '-[
n-[4-(2-trifluoromethoxy) benzyl] piperazine methanoyl]-5,7-dihydroxyl-isoflavones, 7-(
n-propylamine methanoyl)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n-propylamine methanoyl)-5,7-dihydroxyl-isoflavones, 7-(
n-benzylamine methanoyl)-5,4 '-dihydroxyl-isoflavones, 4 '-(
n-benzylamine methanoyl)-5,7-dihydroxyl-isoflavones, 7-[
n-(ethyl acetate) methanoyl]-5,4 '-dihydroxyl-isoflavones, 4 '-[
n-(ethyl acetate) methanoyl]-5,7-dihydroxyl-isoflavones.
2. a pharmaceutical composition, comprises one or more arbitrary isoflavones amino formate compoundss as claimed in claim 1 for the treatment of significant quantity.
3. pharmaceutical composition as claimed in claim 2, is characterized in that this pharmaceutical composition further containing one or more pharmaceutically acceptable carrier or vehicle.
4. the purposes of isoflavones amino formate compounds arbitrarily as claimed in claim 1 in preparation and/or prevention nervus retrogression relative disease medicine.
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| CN104095849B (en) * | 2013-04-02 | 2019-01-01 | 中国医学科学院药物研究所 | The multiple target effect and its improvement learning and memory purposes of one isoflavone derivative |
| CA2965449C (en) * | 2014-10-27 | 2020-11-10 | Cellix Bio Private Limited | Three component salts of fumaric acid monomethyl ester with piperazine or ethylene diamine for the treatment of multiple sclerosis |
| CN106924246A (en) * | 2015-12-31 | 2017-07-07 | 中国医学科学院药物研究所 | Isoflavonoid prevents or treats the purposes of nerve degenerative diseases |
| CN108299367B (en) * | 2018-01-26 | 2022-04-12 | 南阳师范学院 | Celery aglycone carbamate compound, preparation method and application thereof |
| CN108586411A (en) * | 2018-01-26 | 2018-09-28 | 南阳师范学院 | A kind of naringenin carbamate compound, preparation method and application |
| CN115322198A (en) * | 2022-06-13 | 2022-11-11 | 上海工程技术大学 | Pharmaceutical compound based on quinolizidine derivatives and preparation method and application thereof |
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