CN1240671C - N-<l- deoxyglucose alcoho1-1-radical> amino acid and producing process and use thereof - Google Patents

Abstract

The present invention relates to synthesis of N-(1-deoxyglucitol-1-base)-amino acid and pharmaceutical salt, and the purposes of N-(1-deoxyglucitol-1-base)-amino acid and pharmaceutical salt as oral heavy metal expulsion agents, particularly to the purposes of a composition of N-(1-deoxyglucitol-1-base)-amino acid and pharmaceutical salt as oral heavy metal expulsion agents.

Description

N-(1-deoxyglucose alcohol-1-yl)-amino acid and its production and use

Invention field

The present invention relates to N-(1-deoxyglucose alcohol-1-yl)-amino acid and salt that can be medicinal, synthetic method and N-(1-deoxyglucose alcohol-1-yl)-amino acid and salt that can be medicinal be as the purposes of oral row's heavy metal agent, further relates to the composition that contains N-(1-deoxyglucose alcohol-1-yl)-amino acid and salt that can the be medicinal purposes as the agent of oral row's heavy metal.

Background technology

The plumbous for a long time living environment of seriously polluting the mankind.Lead can cause lead poisoning in the human body inner accumulated.Saturnine process is slow, and toxicity is hidden, and is subtle.Though the intravital lead of people mainly from food, also can enter human body by respiratory tract through lead fume and lead dust.Except that organic lead (as tetraethyllead), aluminium and plumbiferous compound generally can not enter human body by complete skin.World Health Organization's report has 400 μ g lead to enter human body through food every day approximately, has 10 μ g lead to enter human body through water approximately, has 26 μ g lead to enter the people through urban air approximately.Along with the increase of accumulation in the human body, toxic reaction appears in body.

Lead is a kind of cumulative toxicity material, is easy to by gastrointestinal absorption.Enter the intravital plumbous part destruction blood of people blood red ball is decomposed, a part is diffused into whole body organ and tissue by blood, goes forward side by side into bone.The lead compound that is deposited in internal organs and the marrow is extremely slow by the speed of getting rid of in the body, forms chronic poisoning gradually.The early symptom of chronic lead poisoning be tired, lose the appetite, lose weight etc.In case chronic poisoning develops again, headache, tinnitus, visual disorder, miscarriage, anaemia, psychiatric disorder just can occur, early wait indefinitely.

Lead contamination is the most serious with the atmosphere Lead contamination.The atmosphere Lead contamination to other Lead contamination in the environment by way of producing fundamental role.The proportion of land pollutant is far longer than the proportion of air.The land pollutant that swims in the atmosphere is in the process of continuous decline.Sedimentation plumbous in the atmosphere can cause ground Lead contamination, waters Lead contamination and food Lead contamination again.Use contains lead salt agricultural chemicals (as lead arsenate) can cause vegetables, melon and fruit, soil and pollution of waterhead.Plumbiferous instrument, pipeline, when the container etc. that is coated with the material package quilt contacts with acidic food, plumbous leachable.Store battery and lead-based paint etc. can cause plumbous pollution to environment.

The lead tolerance of stipulating food such as sauce, soy sauce, vinegar, monosodium glutamate, salt, whole milk powder, wine, cold drink in China's food hygienic standard must not surpass 1mg/kg, and tinned pre-must not surpass 2mg/kg.World Health Organization's suggestion: order the adult temporarily and allow that weekly plumbous intake is 3mg.Normal people's blood lead is generally 15-40 μ g/100g.Blood lead belongs to normal circumstances below 40 μ g/100g.

Abroad the survey showed that in recent years, and blood lead 0.242-0.726 μ mol/L is to fetus, child and adult's health dangerous (Silbergeld EK.Environ, Health Perspect, 1990,89,49.).There are 300-400 ten thousand children in the u.s. department of health estimation U.S. because blood lead makes health be subjected to harm (Us Department of Health and HumanServices.The Nature and Extent of lend Poisoning in Children in theUnited States above 0.72 μ mol/L before 15 years, 1988,2,1.).U.S. CDC in 1991 proposes to prevent children ' s lead poisoning, must manage blood lead is reduced to 0.48 μ mol/L from 1.25 μ mol/L.Report newborn infant tire band blood leads such as Canadian Rhainds in 1993 meet or exceed 0.48 μ mol/L can influence the filial generation neurobehavioral grow (yellow good fortune is relaxed, " health research ", 1995,24,9-10).By being, plumbous toxicity problem causes the concern of countries in the world again.Seek lead discharging medicine efficient, that low toxicity has treatment and prophylactic effect and be still one of focus of the world of medicine's concern so far.

The people takes in plumbous amount every day and is about 300 μ g from food and water, press digestive tube and absorb 10% calculating, and entering the intravital amount of people is 30 μ g; Lead tolerance is 2-5 μ g in the atmosphere, breathes 10m every day ³Air from lung's soakage, absorbs calculating, about 10-25 μ g by 50%.Both close and add up, and taking in plumbous amount every day altogether approximately is 40-50 μ g.Lead is introduced into blood after entering human body by gi tract and respiratory tract.The lead that enters blood is discharged with the urine excrement through kidney, digestive tube mostly.Another part in blood with phosphoric acid hydrogen lead, Phosphoric acid glycerol esters lead compound, protein lead compound or Pb ²⁺Attitude is circulated to whole body.Wherein there is the lead of 91-95% to be present in the bone, is 10 biological half-life with the plumbous form of insoluble tricresyl phosphate ³-10 ⁴My god.Have a small amount of lead to be stored in organs such as liver, spleen, brain and the cell, the transformation period is about 10-40 days.Therefore, bone has constituted the storage pool of human body lead, and blood and soft tissue have constituted the exchange pond of human body lead.Human body is after constantly taking in lead for a long time, and the lead in storage pool and the exchange pond keeps running balance.Under normal circumstances, contact after a certain amount of lead, when inlet and output do not produce harm when equating; If inlet is greater than output, then the amount of Plumbum absorption increases, and corresponding lead in urine output also increases, and does not occur but there is any toxicity symptom, and this kind situation is called Plumbum absorption; If absorbed dose is too much, concentration plumbous in blood and the soft tissue is increased to a certain degree, and lead just produces toxic side effect with susceptibility factor molecule (calmodulin, δ ALAD, chromatin combine the site) combination.Plumbous toxic side effect to blood system mainly shows two aspects red blood cell life span that suppress in the synthetic of oxyphorase and the shortening blood circulation.These influences finally cause the anaemia lead poisoning can suppress the antioxidase system, weaken the ability that body is removed oxyradical, and interior free yl is gathered.Lead poisoning can cause the OH of body inner accumulated, is the main initiator of lipid peroxidation.The content of lipid peroxide significantly raises in the workman's that contact the is plumbous red corpuscle, blood lead concentration and lipid peroxidation of erythrocyte membrane substrate concentration be proportionate (B M Speriewald, A RasCu, K H Schaller, OccpEnviron Med 1999,56,282-283; Zhaolong Gong and Hugh L.Evans.Toxicology and Applied Pharmacology, 1997,144,205-214; Adler AJ.Lead can effect the metabalish of oxygen freeradicals-in hibitsuperoxide dismutase activity.Trace Elem Med, 1993,10,93-96; Su Ya, Zhang Yumin, Cui Jinshan.Plumbous influence to rat red corpuscle and SOD.The Hygiene Toxicology magazine, 1994,8:50; Stohs S J.Bagchi D.Oxidative mechanisms in the toxicity ofmetal ion.Free Radical Bio Ind Med, 1995,18:321-336).Oxyradical not only causes cell injury by the peroxidation of polyunsaturated fatty acid in the microbial film, and can also cause cell injury by the degradation production of fat hydroperoxide.Lead poisoning can influence immune function of human body.Plumbous main passing through to CD ₃Cell (representing total T lymphocyte) and CD ₄The damage effect immune function of human body of cell.The degree of damage of human body cell immunity is relevant with the degree of Plumbum absorption.Plumbous all influential to central nervous system and peripheral nervous system.It is generally acknowledged that plumbous existence to neural toxic action and free radical has substantial connection (Stohs S J.Bagchi D.Oxidativemechanisms in the toxicity of metal ion.Free Radical Bio IndMed, 1995,18,321-336; Stocks J, Dorm andy Tl.The autoxidation ofhuman red cell lipids induced by hydrogen peroxide.Br J Haematoll, 1971,2095-111; Deuticke B, Heller RB, Haest CW.Progressiveoxidative membrane damage in erythrocytes after pulse treatment witht-butyllhydroperoxide.Biochem Biophys Acta, 1987,899,113-124; Lu Xinhua, Shen Guofang, Jin Xiwen.Analysis and discussion that plumbous operating worker free radical changes, radioimmunity magazine, 1997,10,242-243; Scape is great, Liu Shijie, anemia of lead poisoning Study and advance on mechanism, CHINESE JOURNAL OF INTERNAL MEDICINE, 1993,32,840-841; Jain SK.Inexternalizationof phosphatidyl-serine and phosphatidyl-ethanolamine in the membranebilayer and hypercoagulability by the lipid peroxidation of erythrocytes inrats.J Clin Invest, 1985,76-281; Lu Wei.Plumbous neurotoxicity mechanism, foreign medical science hygiology fascicle, 1995,22,341-343).Plumbous damage to genetic material shows as the fracturing effect, and free radical may be the important media of this fracturing effect.Crowd's monitoring shows that blood lead concentration and peripheral blood cells chromosome damage have obvious relation.Experiment confirm is arranged: when blood lead during in 250 μ g/L levels, karyomit(e) has impaired danger; When the blood lead value reaches 350～910 μ g/L, can cause that lead-exposed workers's peripheral blood lymphocyte SCE rate obviously increases ^[17], type mostly is chromatid gap, ruptures and part occurs.Morphological analysis shows that average micronucleus reaches the recall rate of wherein big micronucleus, many micronucleus to a large amount of professional lead-exposed workers's peripheral blood lymphocyte micronucleus, all exceed the professional contactee and the control group workman of benzene far away, very obvious (the Wang Guizhi of plumbous fracturing effect to human body chromosome is described, Liu Shuannian, Hou Yuchun etc., plumbous influence to rat cerebral cell lipid peroxidation and superoxide dismutase activity, the Hygiene Toxicology magazine, 1995,9,175; WHO.Environmental Health Criteria 3.LeadGeneva:WHO, 1997,12) DNA can cause the damage of various ways under the effect of free radical, and as the fracture of strand, crosslinked in proteic, DNA-egg matter is crosslinked etc.Many experiments show free radical have certain cause prominent property (Zhen Qiuchan, Zheng Qinglan, Zhuan Bijia etc., peripheral blood lymphocyte micronucleus form and hereditary effect relation plumbous, benzene, Chinese labour hygiene occupational illness magazine, 1990,8,284-285.).

Human adopt sequestrant treatment metal poisoning since nineteen forties.Traditional plumbous medicine that drives has EDTA, Ca-EDTA (CaEDTA), diethylamide penta acetate (DTPA), calcium calcium trisodium pentetate (CaDTPA), sodium ethylene diamine tetracetate calcium (EDTACa-Na).The tradition that with EDTACa-Na is representative is driven plumbous medicine energy and Pb ²⁺Chelating by glomerular filtration, is discharged by urine.In decades by the saturnine drug of first choice of many country's conduct treatments.Domestic animal experiment is verified, and EDTACa-Na can cause renal tubular necrosis, and the lethal report of injection CaEDTA-4g/d is also arranged clinically.Be that the tradition of representative is driven plumbous medicine digestive tube and absorbed slow with EDTACa-Na, poor selectivity with metal complex, can form stable chelate again with intravital trace element, also discharge the indispensable trace element of a large amount of human bodies (zinc, copper, manganese, iron etc.) in the time of lead discharging.Be that the tradition of representative is driven plumbous medicine and can not be passed cytolemma and enter cell internal abstraction and target cell bonded lead with EDTACa-Na, clinical application is restricted.Containing the plumbous medicine of driving of sulfydryl can form stable comple with entering intravital melts combine, can capture with body in sulfydryl enzyme bonded metal it is excreted, can recover repressed sulfydryl enzymic activity in the active body, thereby reach the toxicide purpose.The plumbous medicine of driving of sulfydryl that contains commonly used has D, L-dimercaptosuccinic acid (MSA), meso-2,3-dimercaptosuccinic acid (DMSA), D, L-2,3-dimercaptopropane sulphonate (DMPS), sodium dimercaptosuccinate (NaDMS), Trolovol (DPA) and N-N-acetylpenicillamine (NAPA).Sodium dimercaptosuccinate is the saturnine drug of first choice of treatment of China's wound usefulness.Sodium dimercaptosuccinate is nontoxic to kidney, and the urinary volume of trace metal increases seldom during the medication, general chronic lead poisoning is equated with CaEDTA with the curative effect of the saturnine colic of acute attack, and be saturnine clinically choice drug.Sodium dimercaptosuccinate can not permeate through cell membranes be brought into play lead-eliminating effect, can aggravate the absorption of human body to lead to a certain extent.DMSA can be oral, absorbs slowlyer, and it is slow to take effect, and has the acute saturnine colic patient of nausea and vomiting to be difficult to use.In addition, the micro-lead in many F﹠B can enter the water-soluble lead complex that gastral DMSA complexing becomes to be easy to absorb with oral, and the lead in the digestive tube is transferred in the blood.Reduce draining and the discharge of increase lead in urine naturally of excrement lead.DMSA is not suitable for the lead poisoning that is caused by the digestive tube absorption.Trolovol and N-N-acetylpenicillamine drive plumbous effect, can be oral, easily cause allergic reaction, and also discharge the mineral substance of needed by human such as a large amount of zinc, copper simultaneously in lead discharging.It is to be noted, the medicine that no matter contains sulfydryl still is that aminocarboxylic acid type medicine does not still have a kind of medicine and can effectively drive away brain lead (J.H.Gra Ziano, J.k Leong The Journal ofPharmacology and Experimental Thera Peuties Vol 206,3,696-700; OleAndersen, Chem.Rev, 1999,99,2683-2710; Landrigan PJ.Lead in themodern work place.Am J Public Health, 1990,80,907-908; ANGLE, C.R:Childhood lead poisoning and its treatment.Annu.Rev.Pharmacol.Toxicol.1993,32,409-434).Vitamins B ₁Be the integral part of auxilliary hydroxylase, can strengthen the activity of enzyme, the plumbous metabolism in vivo of influence.Supply with vitamins B as far as possible ₁Help to eliminate lead and downtrod enzymic activity is brought back to life.The scholar was also once arranged with the calf report of doing experiment, reference's vitamins B abroad ₁Can prevent that lead poisoning from occurring, can prevent lead simultaneously in a organized way, especially the deposition in liver, brain and the sciatic nerve in institute.In addition, vitamins C also can be accumulated by the interior lead of ameliorate body.The preventative vitamins C of throwing not only can effectively reduce Pb-B, can also significantly improve the learning capacity infringement due to plumbous the exposure.

Diethyldithiocar bamic acid (DDC), tetraethyl-thiocarbamoyl dithionic acid salt compounds such as (TTD) are the novel eccritics of a class that grows up the eighties, drive row effect to Cd is better, lead is had certain effect, can form highly insoluble compound with lead and discharge through enteron aisle.But, DDC can form fat-soluble structure with lead, causes distribution more plumbous after the medication.

In recent years find that some albumen can form albumen-metal composite with metal and detoxifcation be arranged or prevent toxic effect.Metallothionein(MT) is rich in halfcystine, and sulfydryl is arranged, and can combine the nuclear inclusion body that forms plumbous albumen composition with lead, thereby reduces plumbous toxicity, quickens lead and excretes.The metallothionein(MT) drink of different concns all can quicken plumbous drainage in vivo, reduces lead concentration in tissue and the bone.

Lead poisoning has subclinical property to the infringement of body, exists in the past as far back as clinical symptom occurring.For fundamentally solving the lead poisoning of this subclinical property, require lead discharging medicine of new generation should have treatment and prevention dual function.The contriver notices, with endogenous sugar and amino acid combination, utilizes sugared poly-hydroxy characteristic to carry the complexing group and enters cell, and is plumbous with the sensitive molecule competition, can reach the toxin expelling effect.

Summary of the invention

An object of the present invention is to provide N-(1-deoxyglucose alcohol-1-yl)-amino acid novel cpd.N-of the present invention (1-deoxyglucose alcohol-1-yl)-amino acid whose chemical structure is shown in following general formula:

R is a hydrogen in general formula, replaces or non-substituted alkyl, and especially C1-C10 alkyl (as hydroxyalkyl) replaces or non-substituted aralkyl, replaces or non-substituted heterocycle group alkyl sulfhydryl group, sulfide group, amide group, acidic group, amido etc.

In preferred embodiments, the invention provides N-(1-deoxyglucose alcohol-1-the yl)-amino acid of general formula I:

R=H ,-CH3 ,-CH ₂OH ,-CH (OH) CH ₃,-CH ₂SH ,-CH ₂CH ₂SCH ₃,-CH (CH ₃) ₂,-CH ₂CH (CH ₃) ₂,-CH ₂COOH, indoles methylene radical ,-CH ₂CH (CH ₃) ₂,-CH ₂(CH ₃) CH ₂CH ₃,-CH ₂(C ₆H ₅), para hydroxybenzene methylene radical ,-CH ₂C (O) NH ₂,-CH ₂CH ₂C (O) NH ₂,-CH ₂CH ₂COOH ,-CH ₂CH ₂CH ₂CH ₂NH ₂,-CH ₂CH ₂CH ₂NHC (=NH) NH ₂Deng.

Another object of the present invention provides the preparation method of above-claimed cpd, comprise glucose and L-amino acid and alkali (for example 45-120 ℃, preferred 50-80 ℃) reaction under heating up, again with the reductive agent reduction, more further with acid-respons.

L-amino acid for example comprises glycine, L-L-Ala, L-Serine, L-Threonine, L-halfcystine, L-methionine(Met), L-Xie Ansuan, L-leucine, L-aspartic acid, L-tryptophane, the L-leucine, the L-leucine, the L-Isoleucine, L-phenylalanine, L-L-glutamic acid, altheine, L-glutaminate, L-arginine etc., or the amino acid whose derivative of these L-.

In the embodiment of the following stated, route according to Fig. 1, with glucose and L-amino acid (glycine, L-L-Ala, L-Serine, L-Threonine, L-halfcystine, L-methionine(Met), L-Xie Ansuan, L-leucine, L-aspartic acid, L-tryptophane etc.) warp and alkali reaction, with reductive agent reaction, more further with acid-respons.The first step in the synthetic route is to generate imines.This step reaction is dehydration, generates the water and the imines of equivalent in the reaction.This is a balanced reaction, and the product imine instability is easy to take place reversed reaction and decomposes back to become raw material.Reactant all is water miscible compound, is insoluble in organic solvent, and reaction has to react this in water makes this reaction usually carry out not exclusively, causes reaction yield not high.Because the imines instability that generates is so product imine is directly carried out next step reduction reaction without separation and purification.

The reductive agent that is fit to comprises the reductive agent that this area is commonly used, for example NaBH ₄, KBH ₄, xitix, mercaptan etc.Because the reason KBH of cost ₄It is comparative optimization.

The acid that is fit to comprises hydrochloric acid, sulfuric acid etc.

(1-deoxyglucose alcohol-1-yl)-amino acid whose polarity is very big owing to product N-, can not adopt the method for conventional column chromatography to separate end product, the present invention adopts storng-acid cation exchange resin as separation means, N-(1-deoxyglucose alcohol-1-yl)-amino acid is separated recrystallization purifying with unreacted amino acid from reaction mixture.

Another object of the present invention provides the purposes of above-claimed cpd.The compound of mutual-through type of the present invention has carried out experimentation on animals.The result shows that the compound oral administration of the present invention administration compound that has of the present invention can obviously lower the lead content of accumulating in multiple internal organs of mouse and bone.Especially R=CH ₂CH ₂SCH ₃Compound of the present invention can obviously lower the lead content of accumulating in mouse brain.Lead content during treating in the blood of animal, ight soil and the urine obviously increases.Thereby the compound that has of the present invention has clear and definite plumbous decorporation ability.

With the blank group relatively, compound of the present invention does not have obvious influence to the content of the iron in the mouse kidney, copper, zinc, manganese and calcium, thereby compound of the present invention is optionally plumbous in the drive row kidney.

The Kunming mouse oral administration once gives compound dosage of the present invention up to the 3.2g/Kg body weight, none death of animal.Thereby compound of the present invention is a low toxicity compounds.In the experiment of short cadmium drive row, compound exhibits of the present invention same obvious treatment effect.

The constructional feature of compound of the present invention is to contain D-glucose glycosyl and various a-amino acid residue in the molecule.Compare with existing heavy metal decorporation medicine, they can be oral, and short heavy metal discharge capacity is strong, and selectivity is high and toxicity is low.

Compound of the present invention can be used for preparing oral decorporation heavy metal medicine, healthcare products and protective foods, described medicine, healthcare products and functional food contain the compound of the present invention of significant quantity, they can also contain this area excipient and additive commonly used, as Magnesium Stearate, Mierocrystalline cellulose, lactose, flavouring agent, sweeting agent etc.Can according to a conventional method compound of the present invention be made suitable oral dosage form.Under the situation of preparation food, compound of the present invention can directly be blended in the food, for example with the amount based on the 0.001-1wt% of food weight.The recommended oral dose of The compounds of this invention is the 5-100mg/kg body weight/day.Compound of the present invention further can be used for preparing medicine, healthcare products and the protective foods of oral lead discharging, and the medicine, healthcare products and the protective foods that are used to prepare decorporation cadmium, mercury, lead, antimony and arsenic.

Description of drawings

Fig. 1 is N-(1-deoxyglucose alcohol-1-yl)-amino acid whose synthetic route chart, and R is respectively H in a-j, CH ₃-,-CH ₂OH ,-CH ₂SH ,-CH ₂CH ₂SCH ₂,-CH (CH ₂) ₂,-CH ₂CH (CH ₂) C ₂H ₅,-CH ₂COOH, the indyl methyl.

One typical curve of instrument when Fig. 2 is the atomic absorption spectrophotometer measure sample.

Another typical curve of instrument when Fig. 3 is the atomic absorption spectrophotometer measure sample.

Embodiment

The invention will be further described below by embodiment.Should be pointed out that these embodiment only are illustrations of the present invention, should not be construed as limitation of the present invention.

Synthesizing of embodiment 1.N-(1-deoxidation-D-1-glucose alcohol radical)-L-aspartic acid (5a)

Sodium hydrate solid 0.40 gram (10mmol) is dissolved in the 3ml water, stirring at room, treat that solution returns to room temperature after, add aspartic acid 1.33g (10mmol), after the dissolving, add D-glucose 1.80g (10mmol), stirring at room is after the transparent clarification of solution, feed argon gas to reaction system, at 50 ℃-60 ℃ reaction 5h, solution colour becomes pale brown look, stops heating.After treating that temperature returns to room temperature, reactant transfer to wide-necked bottle, is added POTASSIUM BOROHYDRIDE 1.62g (30mmol) in batches, reaction 120h obtains yellow thick liquid.Reaction system is placed under the ice bath, drip concentrated hydrochloric acid, regulator solution pH 2-2.5, the adularescent solid is separated out.Suction filtration is removed white solid, and filtrate decompression adds dehydrated alcohol after concentrating and removing portion water again, leaves standstill the back suction filtration and removes the white solid of separating out, and filtrate decompression concentrates.Repeat aforesaid operations repeatedly, remove the white solid of separating out as far as possible.This filtrate is directly gone up strong acid cation exchange resin column, use earlier the distilled water wash-out, remove unreacted sugar component, use the N-methylmorpholine aqueous solution wash-out of 3%-5% again, collect the product component, remove the water in the product component, residue recrystallization (water-ethanol) obtains white solid 257mg (9%).Mp：171.3-172.6℃；[α] _D ²⁵°：-9.71°(C，2.06，H ₂O)。

Rf=0.06 (chloroform: methyl alcohol: water=1: 1: 0.2).IR(cm ^-1)：3569.01，3366.11，3233.11，2894.35，2367.61，1730.45，1617.20，1559.58，1397.39，1175.88，1087.37，826.83，676.25，610.82. ¹H NMR(500MHZ，D ₂O)：3.37(dd，J＝3.5Hz，J＝13Hz，1H，H ₁a)，3.28(dd，J＝9Hz，J＝13Hz，1H，H ₁b)，4.15(m，H ₂)，3.86(dd，J＝3Hz，J＝5Hz，H ₃)，3.81(dd，J＝3Hz，J＝12Hz，1H，H ₄)，3.75(m，1H，H ₅)，3.65(m，2H，H ₆)，4.03(dd，J＝5Hz，J＝7Hz，1H，H ₂’)，3.08(dd，J＝5Hz，J＝18Hz，1H，H ₃a’)，3.01(dd，J＝7Hz，J＝18Hz，1H，H ₃b’)FAB/MS：298[M+1] ^-

Synthesizing of embodiment 2.N-(1-deoxidation-D-1-glucose alcohol radical)-L-glycine (5b)

Sodium hydrate solid 1.20 grams (30mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add glycine 2.25g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol); stirring at room after the transparent clarification of solution, feeds argon shield to reaction system; be heated to 50-60 ℃ of reaction 5hr; solution colour becomes pale brown look, the temperature of reaction system is returned to room temperature and is transferred in the wide-necked bottle, adds POTASSIUM BOROHYDRIDE 4.86g (90mmol) in batches; reaction 5 obtains yellow thick liquid round the clock.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 1.148g (16%).R _f=0.2 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：181.9-182.4℃；[α] _D ^25°：-17.22(C，2.09，H ₂O)。IR(cm ^-1)：3531.62，3241.56，2962.72，2897.23，2365.02，1627.40，1560.93，1402.14，1377.90，1060.91，1036.80，848.01，690.87，578.62； ¹H NMR(500MHZ，D ₂O)：3.29(dd，J＝3.5Hz，J＝13Hz，1H，H ₁a)，3.21(dd，J＝9.5Hz，J＝13Hz，1H，H ₁b)，4.13(m，1H，H ₂)，3.83(m，1H，H ₃)，3.81(m，1H，H ₄)，3.76(m，1H，H ₅)，3.66(m，1H，2H，H ₆)；FAB/MS：240[M+1] ^-.

Synthesizing of embodiment 3.N-(1-deoxidation-D-1-glucose alcohol radical)-L-Serine (5c)

Sodium hydrate solid 1.20 grams (30mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add Serine 3.15g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol); stirring at room after the transparent clarification of solution, feeds argon shield to reaction system; be heated to 50-60 ℃ of reaction 5h; solution colour becomes pale brown look, the temperature of reaction system is returned to room temperature and is transferred in the wide-necked bottle, adds POTASSIUM BOROHYDRIDE 4.86g (90mmol) in batches; reaction carries out 5 round the clock, obtains yellow thick liquid.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 1.18g (14.7%).Rf=0.22 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：195.4-197.5℃；[α] _D ^25°：-11.94°(C，2.01，H ₂O)。IR(cm ^-1)：3221.93，2941.06，2900.56，1620.90，1564.84，1424.11，1336.53，1093.19，1040.23，705.85； ¹H NMR(500MHZ，D ₂O)：3.36(dd，J＝3Hz，J＝13Hz，1H，H ₁a)，3.25(dd，J＝10Hz，J＝13Hz，1H，H ₁b)，4.16(m，1H，H ₂)，3.83(dd，J＝1Hz，J＝3Hz，1H，H ₃)，3.80(d，J＝3Hz，1H，H ₄)，3.76(m，1H，H ₅)，3.66(m，2H，H ₆)，3.85(t，J＝2.5Hz，1H，H ₂’)，4.06(dd，J＝3.5Hz，J＝12.5Hz，1H，H ₃’)，3.99(dd，J＝5Hz，J＝12.5Hz，1H，H ₄’)FAB/MS：270[M+1] ^-.

Synthesizing of embodiment 4.N-(1-deoxidation-D-1-glucose alcohol radical)-L-Threonine (5d)

Sodium hydrate solid 1.20 grams (30mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add Threonine 3.57g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol); stirring at room after the transparent clarification of solution, feeds argon shield to reaction system; be heated to 50-60 ℃ of reaction 5h; solution colour becomes pale brown look, the temperature of reaction system is returned to room temperature and is transferred in the wide-necked bottle, adds POTASSIUM BOROHYDRIDE 4.86g (90mmol) in batches; reaction carries out 5 round the clock, obtains yellow thick liquid.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 2.07g (24.4%).R _f=0.15 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：195.4-196.6℃；{α] _D ^25°：-28.57°(C，2.10，H ₂O)。IR(cm ^-1)：3421.32，2975.37，2938.80，1612.18，1571.34，1415.43，1385.47，1083.60，1044.63，840.85，757.81，731.36； ¹HNMR(500MHZ，D ₂O)：3.30(dd，J＝3Hz，J＝13Hz，1H，H ₁a)，3.20(dd，J＝10Hz，J＝13Hz，1H，H ₁b)，4.15(m，1H，H ₂)，3.82(m，1H，H ₃)，3.80(m，1H，H ₄)，3.75(m，1H，H ₅)，3.64(m，2H，H ₆)，3.51(d，1H，H ₂’)，4.09(m，1H，H ₃’)，1.34(d，J＝3Hz，1H，H ₄’)；FAB/MS：284[M+1] ^-.

Synthesizing of embodiment 5.N-(1-deoxidation-D-1-glucose alcohol radical)-L-halfcystine (5e)

Sodium hydrate solid 2.40 grams (60mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add cysteine hydrochloride 4.72g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol); stirring at room after the transparent clarification of solution, feeds argon shield to reaction system; be heated to 50-60 ℃ of reaction 5h; solution colour becomes pale brown look, the temperature of reaction system is returned to room temperature and is transferred in the wide-necked bottle, adds POTASSIUM BOROHYDRIDE 4.86g (90mmol) in batches; reaction carries out 5 round the clock, obtains yellow thick liquid.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 865mg (10.2%).R _f=0.23 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：171-172.1℃；[α] _D ^25°：-8.74°(C，2.06，H ₂O)。IR(cm ^-1)：3274.87，2974.89，2935.68，1606.84，1567.15，1417.26，1391.26，1082.30，1035.79，695.19，631.88； ¹H NMR(500MHZ，D ₂O)：3.35(dd，J＝3Hz，J＝13Hz，1H，H ₁a)，3.24(dd，J＝9.5Hz，J＝13Hz，1H，H ₁b)，4.16(m，1H，H ₂)，3.86(dd，J＝3Hz，J＝4.5Hz，1H，H ₃)，3.81(dd，J＝3Hz，J＝12Hz，1H，H ₄)，3.76(m，1H，H ₅)，3.65(m，2H，H ₆)，3.97(t，J＝5Hz，1H，H ₂’)，3.15(dd，J＝18Hz，J＝5Hz，1H，H ₃’a)，3.08(dd，J＝18Hz，J＝5Hz，1H，H ₃’b)；FAB/MS：285[M+1] ^-.

Synthesizing of embodiment 6.N-(1-deoxidation-D-1-glucose alcohol radical)-L-methionine(Met) (5f)

Sodium hydrate solid 1.20 grams (30mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add methionine(Met) 4.47g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol), stirring at room is after the transparent clarification of solution; feed argon shield to reaction system; be heated to 50 to 60 ℃, reaction 5hr, solution colour becomes pale brown look; the temperature of reaction system is returned to room temperature and be transferred in the wide-necked bottle; add POTASSIUM BOROHYDRIDE 4.86g (90mmol), reaction carries out 5 round the clock, obtains yellow thick liquid in batches.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 1.992g (21.1%).R _f=0.43 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：197.5-198.9℃；[α] _D ^25°：-8.49°(C，2.12，H ₂O)。IR(cm ^-1)：3464.30，3431.33，3291.33，3116.84，2929.67，2340.33，1601.42，1553.70，1433.36，1397.98，1089.19，849.19，691.75； ¹H NMR(500MHZ，D ₂O)：3.28(dd，J＝3Hz，J＝13Hz，1H，H ₁a)，3.19(dd，J＝10Hz，J＝13Hz，1H，H ₁b)，4.12(m，1H，H ₂)，3.83(m，2H，H ₃ & H ₄)，3.76(m，1H，H ₅)，3.65(d，J＝6Hz，1H，H ₆a)，3.63(dd，J＝1.5Hz，J＝4Hz，1H，H ₆b)，3.81(t，J＝3Hz，1H，H ₂’)，2.65(m，2H，H ₃’)，2.19(q，J＝7Hz，2H，H ₄’)，2.13(s，3H，H ₅’)；FAB：314[M+1] ^-.

Synthesizing of embodiment 7.N-(1-deoxidation-D-1-glucose alcohol radical)-L-leucine (5g)

Sodium hydrate solid 1.20 grams (30mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add leucine 3.93g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol); stirring at room after the transparent clarification of solution, feeds argon shield to reaction system; be heated to 50-60 ℃ of reaction 5hr; solution colour becomes pale brown look, the temperature of reaction system is returned to room temperature and is transferred in the wide-necked bottle, adds POTASSIUM BOROHYDRIDE 4.86g (90mmol) in batches; reaction carries out 5 round the clock, obtains yellow thick liquid.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 420mg (5%).R _f=0.62 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：207-208.3℃；[α] _D ^25°：-6.80°(C，2.06，H ₂O)。

IR(cm ^-1)：3364.86，3096.59，2962.29，2923.81，1615.50，1431.86，1373.94，1294.41，1082.86，1043.85，761.35，676.95； ¹H NMR(500MHZ，D ₂O)：3.26(dd，J＝3Hz，J＝13Hz，1H，H ₁a)，3.14(dd，J＝10Hz，J＝13Hz，1H，H ₁b)，4.01(m，1H，H ₂)，3.81(m，1H，H ₃)，3.80(m，1H，H ₄)，3.75(m，1H，H ₅)，3.63(m，2H，H ₆)，3.68(t，J＝6Hz，1H，H ₂’)，1.72(m，1H，H ₄’)，1.70(m，2H，H ₃’)，0.95(dd，J＝3Hz，J＝6Hz，6H，H ₅’)；FAB：295[M+1] ^-.

Synthesizing of embodiment 8.N-(1-deoxidation-D-1-glucose alcohol radical)-L-L-Ala (5h)

Sodium hydrate solid 0.40 gram (10mmol) is dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add L-Ala 0.89g (10mmol); after the dissolving; add D-glucose 1.80g (10mmol), stirring at room is after the transparent clarification of solution; feed argon shield to reaction system; be heated to 50 to 60 ℃, reaction 5hr, solution colour becomes pale brown look; the temperature of reaction system is returned to room temperature and be transferred in the wide-necked bottle; add POTASSIUM BOROHYDRIDE 2.72g (50mmol), reaction carries out 5 round the clock, obtains yellow thick liquid in batches.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 765mg (30%).

R _f=0.2 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：201.5-202.1℃；[α] _D ^25°：-14.00°(C，2.00，H ₂O)。IR(cm ^-1)：3419.57，3273.45，2973.11，2905.13，1621.50，1586.88，1423.75，1399.86，1082.98，1037.97，704.19，667.77；FAB/MS：254[M+1] ^-.

Synthesizing of embodiment 9.N-(1-deoxidation-D-1-glucose alcohol radical)-L-Xie Ansuan (5i)

Sodium hydrate solid 1.20 grams (30mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add Xie Ansuan 3.51g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol), stirring at room is after the transparent clarification of solution; feed argon shield to reaction system; be heated to 50 to 60 ℃, reaction 5hr, solution colour becomes pale brown look; the temperature of reaction system is returned to room temperature and be transferred in the wide-necked bottle; add POTASSIUM BOROHYDRIDE 2.72g (50mmol), reaction carries out 5 round the clock, obtains yellow thick liquid in batches.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 331mg (4%).

Rf=0.51 (chloroform: methyl alcohol: water=1: 1: 0.2).Mp：216-217℃；[α] _D ^25°：-3.96°(C，2.02，H ₂O)。

IR(cm ^-1)：3338.55，3186.43，2971.56，2939.73，2362.06，1603.39，1551.31，1420.64，1317.92，1080.40，1034.74，825.20，694.80，617.32； ¹H NMR(500MHZ，D ₂O)：3.27(dd，J＝3Hz，J＝13Hz，1H，H ₁a)，3.17(dd，J＝10Hz，J＝13Hz，1H，H ₁b)，4.13(m，1H，H ₂)，3.83(m，1H，H ₃)，3.82(m，H ₄)，3.74(m，H ₅)，3.64(m，2H，H ₆)，3.58(dd，J＝4.5Hz，J＝16Hz，1H，H ₂’)，2.26(m，1H，H ₃’)，1.05(dd，J＝7Hz，J＝16Hz，6H，H ₄’)；FAB/MS：282[M+1] ^-.

Synthesizing of embodiment 10.N-(1-deoxidation-D-1-glucose alcohol radical)-L-tryptophane (5j)

Sodium hydrate solid 1.20 grams (30mmol) are dissolved in the 3ml water; stirring at room; after treating that solution returns to room temperature; add tryptophane 6.12g (30mmol); after the dissolving; add D-glucose 5.40g (30mmol); stirring at room after the transparent clarification of solution, feeds argon shield to reaction system; be heated to 50-60 ℃ of reaction 5h; solution colour becomes pale brown look, the temperature of reaction system is returned to room temperature and is transferred in the wide-necked bottle, adds POTASSIUM BOROHYDRIDE 4.86g (50mmol) in batches; reaction carries out 5 round the clock, obtains yellow thick liquid.Post-treating method according to embodiment 1 carries out aftertreatment to reaction product, obtains white solid 1.335g (12.1%).

R _f=0.2 (chloroform: methyl alcohol: water=1: 1: 0.2).mp：205.5-207.0℃；[α] _D ^25°：+13.00°(C，2.00，DMSO)。IR(cm ^-1)：3407.12，3352.67，3094.81，2967.74，2916.26，1617.46，1399.95，1354.16，1080.33，1041.45，741.58，675.00，534.21；FAB/MS：369[M+1] ^-。

The preparation of embodiment 11.N-(1-deoxidation-D-1-glucose alcohol radical)-L-amidates

The compounds of this invention 0.1mmol with wait for example sodium hydroxide of alkali that mole can be medicinal, potassium hydroxide, basic aminoacids is arginine for example, Methionin waits the acid hydrochloric acid for example that mole can be medicinal, citric acid, and acidic amino acid aspartic acid for example, the L-glutamic acid reaction makes corresponding N-(1-deoxidation-D-1-glucose alcohol radical)-L-amidates, and yield is more than 95%.

Embodiment 12. preparation of compositions

The compounds of this invention 150mg, Magnesium Stearate 10mg, lactose 200mg, starch 140mg tablet producing technology routinely makes tablet.

Embodiment 13. determinations of activity

Laboratory animal: healthy ICR male mice, body weight 18-25g.Contaminating mode: be made into lead acetate water solution with deionized water, concentration is Pb (CH ₃COO) ₂3H ₂O8.2mg/kg.Abdominal injection (20g needs 0.2ml) was injected 7 days continuously, after the 48h, laboratory animal was divided into 10 groups at random, 10 every group at interval.Administering mode: all animals are stopping the 48hr start injection administration afterwards of contaminating, positive controls and administration group are all by 0.4mmol/kg (being dissolved in the 0.2ml deionized water) abdominal injection, blank group abdominal injection 0.9% physiological saline, set group is as follows: Pb and 0.9%saline; Pb and DL-PA; Pb and 5a; Pb and 5b; Pb and 5c; Pb and 5d; Pb and 5e; Pb and 5f; Pb and 5g; Pb and 5h; Pb and 5i; Pb and 5j; Pb and 5k; Sample collection: after the administration every day 2hr, begin to collect urine within the mouse 3-4hr; Administration was collected stool in mice in second day as fecal sample the day before yesterday.Continue 5 days, every day 1 group of mouse urine, excrement respectively as a sample.After the last administration 24hr, mouse is taken off neck put to death, observe internal organ and change, separation is also taken out liver, kidney, left side femur and brain as sample.Sample process: all biological specimens are all used HNO ₃: HCLO ₄(3: 1) are nitrated on hot plate to be occurred to the adularescent solid, with the high purity water dissolving and be transferred to constant volume in the volumetric flask, with the plumbous content of Varian spectr AA40 atomic absorption spectrophotometer (graphite furnace method).Data processing: since each when using the atomic absorption spectrophotometer measure sample state of instrument inconsistent, thereby all want the configuration standard curve during each measure sample, here list the part of standards curve, as table 1 and Fig. 2 and table 2 and shown in Figure 3, sincerely with example.

Table 1

C(ug/ml)	0.05	0.10	0.15	0.20	0.25
						ABS	0.190	0.490	0.663	0.922	1.089

Table 2

C(ug/ml)	0.05	0.10	0.15	0.20	0.25
						ABS	0.173	0.367	0.711	0.928	1.083

With atomic absorption spectrophotometer institute test sample in this plumbous concentration carry out data processing, calculate lead content in every gram sample (urine is lead content in per 0.5 milliliter of sample), carry out variance analysis, and administration group and blank group and positive controls be compared as follows:

Lead content in table 1. mouse tissue (X ± SE ug/g)

Group	Bone lead content (ug/g)	Brain lead content (ug/g)	Kidney lead content (ug/g)	Liver lead content (ug/g)	Excrement lead content (ug/g)	Lead content in urine (ug/ml)
							NS	55.203±5.429	2.392±0.385	8.442±2.794	9.960±1.500	9.173±2.638	0.853±0.151
DL-PA	45.410±6.171	1.135±0.349	5.991±1.412	2.825±1.253	11.482±2.795	0.534±0.053
							5h	45.867±7.764 c	1.215±0.116 c	4.946±1.495 b	12.688±1.453 c	17.320±2.525 ce	1.209±0.224 af
5g	63.249±7.129	1.973±0.235 b	7.984±2.345	11.208±2.033	10.304±1.016 a	1.110±0.323 e
							5f	45.011±7.623 c	0.963±0.103 c	6.099±0.852 a	7.179±0.551 c	11.314±1.752 a	1.316±0.201 bf
5j	55.659±5.406	1.928±0.288 b	6.819±1.094	10.379±1.261	11.240±1.872 a	1.518±0.316 bf
							5b	41.565±8.776 cd	1.185±0.174 c	6.093±1.938	6.783±0.856 c	12.420±0.803 b	1.429±0.230 bf
5e	25.798±4.376 cf	1.113±0.130 c	2.974±0.465 ce	10.803±1.120	17.320±2.525	1.602±0.263 bf
							5a	61.105±8.148	2.187±0.257	7.538±1.705	10.875±1.427	10.875±1.427	0.966±0.165 e
5d	47.311±9.446 b	1.168±0.154 c	6.307±1.131 a	7.661±1.205 ac	12.930±0.851	1.268±0.274 ae
							5c	57.672±4.245	1.944±0.162 b	7.676±0.757	9.439±1.005	10.214±1.705	0.946±0.354
5i	57.476±4.649	2.647±0.458	7.981±0.901 a	11.919±1.762	16.277±1.723	1.171±0.316 ce

Annotate: n=15; A) compare p＜0.05 with the physiological saline group; B) compare p＜0.01 with the physiological saline group; C). compare p＜0.001 with the physiological saline group; D). compare p＜0.05 with the DL-PA group; E) compare p＜0.01 with the DL-PA group; F: compare with the DL-PA group, p＜0.001, (n=10).

Behind the drug treatment, content plumbous in brain, bone, the kidney significantly descends, compound 5h, and 5d, 5e, 5f and 5g have good lead discharging activity, present significant difference with the contrast of physiological saline group.Compare the same lead discharging activity that demonstrates of compound 5f with the DL-PA group with 5e.The content of the lead in the ight soil of administration group and the urine obviously will be higher than the physiological saline group, and the content of the excrement lead of the same compound 5g with 5e and 5a group presents significant difference than the lead content height in the positive controls.All target compounds corresponding group the lead content in urine significance be higher than the corresponding lead content in urine of organizing of positive drug institute.Illustrate that this compounds can promote drainage plumbous in the body, the favourable and intravital lead of removing reduces plumbous toxic side effect.

Compound of the present invention is to the lead discharging effect of the tissue of mouse and organ and inequality, but demonstrates certain selectivity, and is the same with 5e, compound 5g, and 5f, 5h and 5d not only have the effect of good drive row brain lead, also demonstrate the activity with drive row kidney lead.The same with 5e, compound 5g, 5f, 5h and 5d have the effect of good drive row bone lead.In identical histoorgan, the effect of target compound also has nothing in common with each other.The structure that these results all are derived from them has difference, and different structures has caused different physico-chemical properties, thereby has produced different biologic activity.The lead discharging result of different histoorgans is discussed below.

Bone is a storage vault plumbous in the human body, and entering that the intravital lead of people has more than 90% is to be stored in the bone with phosphatic form.They can enter target organs such as liver, kidney, brain and produce toxic side effect through blood along with the carrying out of internal metabolism process.The content that effectively reduces bone lead will help the reduction of integral level plumbous in the human body.In the administration group, the same with 5e, 5g, 5f and 5h have certain expulsion action for bone lead.Say that on the whole these three compounds belong to fat-soluble bigger compound in target compound, their lead discharging activity is better than fat-soluble little compound.5g and 5i, 5h and 5b, 5d compares with 5c, the structural similitude of the former with the latter, just the former amino acid side chain is longer than the latter's amino acid side chain, makes the fat-soluble stronger of compound of the present invention, and this has also increased the ability of compound permeates cell membranes of the present invention, make compound of the present invention can in cell, compete the lead in the chelating born of the same parents, promote discharge plumbous in the cell.

Plumbous very big to neural damage harm, especially intelligence growth and the neurobehavioral harm to children is very big.Developing country is because industrial pollution and living environment condition are poor, and problem is particularly outstanding.At present, this problem has caused concern.At present, still not having medicine can address this problem pointedly.By pharmacological evaluation, find to have in the compound of the present invention some to have the effect of good drive row brain lead.

The same with 5e, compound 5h, 5f, 5b and 5d have the pharmacologically active of good drive row brain lead.They can make the brain lead content reduce nearly 50%.In general, compound 5h, 5f, 5b and 5d are than 5a, and the liposoluble of 5c and 5i is big, their drive row brain lead more effective; The latter's is fat-soluble less, and the effect of drive row brain lead is relatively poor.5h and 5g, 5f and 5e, 5b and 5a, four groups of compounds of 5d and 5c are compared, and the former lead discharging activity is proportionate with the fat-soluble of them greater than the latter.Fat-soluble big compound is easier to pass hemato encephalic barrier, can with the aluminium chelating in the brain, promote brain aluminium to discharge.

Lead can cause acute plumbous ephrosis and Chronic lead ephrosis.Two ekalead ephrosis all can produce damage to proximal convoluted tubule by renal cells, cause the proximal convoluted tubule dysfunction.The present invention estimates the plumbous activity of the drive row kidney of compound of the present invention.The same with 5e, compound 5h, 5f, 5b and 5d have certain lead discharging activity.5h, 5b and 5d are than 5g, and 5a and 5c demonstrate lead discharging activity preferably.This can sum up equally with in they relative big fat-soluble permeates cell membranes that causes being easy to, plumbous with the sensitive molecule competition in the born of the same parents, promote discharge plumbous in the cell.

Liver is the main metabolic organ of human body, during plumbous too high levels, can produce infringement to the eubolism of whole human body in the liver.In time the excessive lead of removing in the liver is very necessary.In compound of the present invention, 5f, 5b and 5d have the drive row activity to excessive lead in the liver.

To the comparison that lead content carried out in ight soil and the urine, compound of the present invention as can be seen all makes excrement content plumbous and lead in urine increase.Compound promoted of the present invention has been described plumbous to excrete with ight soil through digestive tube in body.After compound of the present invention and the plumbous chelating, a plurality of hydroxyls of introducing in the inner complex molecule, carboxyl and the amino polarity of molecule that makes increase, and increase the bile excretion rate, enter duodenum through bile excretion, excrete with ight soil at last.Chemical combination 5h of the present invention, 5b and 5d are than 5g, and 5a and 5c can promote lead to drain by digestive tube better.The former fat-soluble is better than the latter, behind the abdominal injection, is easy to enter the histoorgan cell, enters circulation of blood with post-absorption, and through liver, bile excretion excretes with ight soil.

Renal excretion is a drug disposition excretory main path, also is the main path of getting rid of heavy metal.Evaluation to compound of the present invention shows that compound of the present invention all obviously increases the content of urine aluminium, has promoted plumbous discharge from urinary system.Compound of the present invention has very big polarity, absorbs easily to enter blood, forms high polar inner complex with the blood lead chelating, makes uriniferous tubules heavily absorb reduction, has promoted plumbous drainage.

The excrement of administration mouse content plumbous and lead in urine being compared, can see the content of the content of excrement lead apparently higher than lead in urine, approximately is its 15 to 20 times.Can discuss when discharging body accumulation plumbous effectively for compound of the present invention, most of plumbous by bile excretion, small portion is plumbous to be drained through urinary system.This situation has reduced the lead load of kidney, has also reduced the re-absorbed probability of uriniferous tubules simultaneously, plays a very good protection for kidney.

Claims (6)

1, the N-of general formula I (1-deoxyglucose alcohol-1-yl)-amino-acid compound:

R=-CH wherein ₂OH ,-CH ₂CH ₂SCH ₃,-CH (CH ₃) ₂,-CH ₂CH (CH ₃) ₂,-CH ₂COOH, indoles methylene radical ,-CH ₂CH (CH ₃) ₂,-CH ₂(CH ₃) CH ₂CH ₃, the para hydroxybenzene methylene radical ,-CH ₂C (O) NH ₂,-CH ₂CH ₂C (O) NH ₂,-CH ₂CH ₂COOH ,-CH ₂CH ₂CH ₂CH ₂NH ₂Or-CH ₂CH ₂CH ₂NHC (=NH) NH ₂

2, the purposes of the compound of general formula I in preparation row heavy metal medicine,

Wherein R=H ,-CH ₃,-CH ₂OH ,-CH (OH) CH ₃,-CH ₂CH ₂SCH ₃,-CH (CH ₃) ₂,-CH ₂CH (CH ₃) ₂,-CH ₂COOH, indoles methylene radical ,-CH ₂CH (CH ₃) ₂,-CH ₂(CH ₃) CH ₂CH ₃,-CH ₂(C ₆H ₅), the para hydroxybenzene methylene radical ,-CH ₂C (O) NH ₂,-CH ₂CH ₂C (O) NH ₂,-CH ₂CH ₂COOH ,-CH ₂CH ₂CH ₂CH ₂NH ₂Or-CH ₂CH ₂CH ₂NHC (=NH) NH ₂

3, purposes as claimed in claim 2, wherein heavy metal is cadmium, mercury, lead, antimony or arsenic or their arbitrary combination.

4, purposes as claimed in claim 3, wherein heavy metal is plumbous.

5, the row's heavy metal pharmaceutical composition that contains claim 1 compound of significant quantity.

6, the healthcare products or the food that contain claim 1 compound of significant quantity.

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