CN102229564A - 4-(7-chlorine-4aminoquinoline)-5,6,7,8-tetrahydro-alpha-naphthol derivatives, preparation method and application thereof - Google Patents
4-(7-chlorine-4aminoquinoline)-5,6,7,8-tetrahydro-alpha-naphthol derivatives, preparation method and application thereof Download PDFInfo
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- 0 *Cc1cc(Nc2c(ccc(Cl)c3)c3ncc2)c(CCCC2)c2c1O Chemical compound *Cc1cc(Nc2c(ccc(Cl)c3)c3ncc2)c(CCCC2)c2c1O 0.000 description 1
- BHPDJODNITVKPM-UHFFFAOYSA-N CC(C(C=C=[U])O)(N)[N]#C Chemical compound CC(C(C=C=[U])O)(N)[N]#C BHPDJODNITVKPM-UHFFFAOYSA-N 0.000 description 1
- HWVOBQPSGWIQHP-UHFFFAOYSA-N CC(C[N]#C)COC Chemical compound CC(C[N]#C)COC HWVOBQPSGWIQHP-UHFFFAOYSA-N 0.000 description 1
- OSPSUZJXBQPSCV-UHFFFAOYSA-N CCC(N)([N]#C)[O]#C Chemical compound CCC(N)([N]#C)[O]#C OSPSUZJXBQPSCV-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a class of 4-(7-chlorine-4aminoquinoline)-5,6,7,8-tetrahydro-alpha-naphthol derivatives, a preparation method and application thereof. As shown in the structural formula I of the compound provided by the invention, R is a straight chain or branched alkylamino radical containing 1-2 hydroxy and 3-4 carbon atoms, a straight chain or branched enamine group containing 3 carbon atoms, or substituted alkyl 5-6 nitrogen heterocyclic radical. Based on the medicament naphthoquine phosphate used in clinical practice, part of its side chain structure of terbufos amine group is modified to produce a new compound. It is proved through drug effect tests that the compound provided by the invention has a better anti-calamity activity and lower drug resistance and toxicity.
Description
Technical field
The present invention relates to 4-(7-chloro-4 quinolylamines)-5,6,7,8-tetrahydrochysene-naphthyl alcohol derivative and preparation method thereof and application.
Background technology
Malaria is to be a kind of communicable disease of broadcasting media with the mosquito.It is the widest popular in the world, a parasitosis that harm is maximum, also is one of sanitarian outstanding problem in the world today.According to 108 countries and regions of having an appointment, the WHO report whole world, nearly half population in the whole world is subjected to the harm of malaria, most areas, Africa on the south the Sahara, and Asia, Latin America, the Middle East and Europe also are affected.Wherein the whole year in 2008 2.74 hundred million clinical report case is just arranged, nearly million people's death is arranged, great majority are African children below 5 years old, die from this sick children's number up to 20% of death of child sum.Though people have developed the antimalarial agent of numerous species type,, cause many geographic plasmodiums resistance in various degree to occur along with the frequent use of these medicines.So the research and development low toxicity has no drug resistance and has prevention concurrently and the antimalarial drug of therapeutic action is very necessary.
Summary of the invention
The purpose of this invention is to provide a class 4-(7-chloro-4 quinolylamines)-5,6,7,8-tetrahydrochysene-naphthyl alcohol derivative and preparation method thereof.
The structural formula of 4-provided by the present invention (7-chloro-4 quinolylamines)-5,6,7,8-tetrahydrochysene-naphthyl alcohol derivative is suc as formula shown in the I:
Among the formula I, R contains 1～2 hydroxyl and has the 5-6 member heterocyclic ring containing nitrogen base that the straight or branched alkylamino radical of 3～4 carbon atoms, the straight or branched enamine base with 3 carbon atoms or alkyl replace.
Described R can further be selected from any one in the following radicals:
The pharmacy acceptable salt of compound shown in the formula I also belongs to protection scope of the present invention.The pharmacy acceptable salt that is applicable to this compound specifically can be phosphoric acid salt, hydrochloride, vitriol, nitrate, acetate, formate or maleate.
The method of preparation I compound provided by the invention comprises the steps:
1) formula II compound and formula III compound are carried out back flow reaction in the mixed solvent of ethanol and water, obtain compound shown in the formula IV;
2) compound shown in the formula IV, formaldehyde and formula V compound are reacted in solvent, or the 5-6 member heterocyclic ring containing nitrogen compound of compound shown in the formula IV, formaldehyde and alkyl replacement is reacted in solvent, obtain compound shown in the formula I; Described solvent is the mixed solvent of ethanol or ethanol and water;
NH
2R
2
(formula V)
Among the formula V, R
2For containing 1～2 hydroxyl and having the straight or branched alkylamino radical of 3～4 carbon atoms or have the straight or branched enamine base of 3 carbon atoms.
Wherein, in the step 1), the mass ratio of described formula II compound and formula III compound is 1: (1～1.2); The volume ratio of ethanol and water is 1 in the described mixed solvent: (0.8～1.2); The time of described back flow reaction is 6～8 hours.
Step 2) in, the volume ratio of ethanol and water is (85-100) in the mixed solvent of described ethanol and water: (15-0); The temperature of described reaction is 60～84 ℃, and the time is 10-96 hour.
R among the described formula V
2Can further be selected from the following radicals any one:
The 5-6 member heterocyclic ring containing nitrogen compound that described alkyl replaces is the 4-methyl piperidine.
The method of the salt of preparation I compound comprises the steps: formula I compound is dissolved in the dehydrated alcohol, and to wherein adding organic acid or mineral acid reacts, promptly gets the salt of formula I compound.
Described organic acid can be formic acid, acetic acid or toxilic acid; Described mineral acid can be phosphoric acid, hydrochloric acid, sulfuric acid or nitric acid.
In order to obtain the product of purifying, also the salt that above-mentioned steps can be obtained places the aqueous ethanolic solution of 40%-95% to carry out recrystallization.
The present invention also provides the application of formula I compound or its pharmacy acceptable salt.
To be formula I compound or its pharmacy acceptable salt prevent and/or treat application in the malaria medicine in preparation in application provided by the present invention.
The present invention also protects a kind of medicine and a kind of pharmaceutical composition that prevents and/or treats malaria that prevents and/or treats malaria.
The activeconstituents of described medicine is formula I compound or its pharmacy acceptable salt.
Described pharmaceutical composition, its composition comprise formula I compound or its pharmacy acceptable salt, and pharmaceutically acceptable carrier.
Described carrier comprises thinner, vehicle, weighting agent, tackiness agent, wetting agent, disintegrating agent, absorption enhancer, tensio-active agent, absorption carrier, lubricant of pharmaceutical field routine etc.
The medicine that prevents and/or treats malaria with formula I compound or the preparation of its pharmacy acceptable salt can be made various ways such as injection liquid, tablet, pulvis, granule, capsule, oral liquid, paste, creme.The medicine of above-mentioned various formulations all can be according to the ordinary method preparation of pharmaceutical field.
The described pharmaceutical composition that prevents and/or treats malaria can import body such as muscle, intracutaneous, subcutaneous, vein, mucosal tissue by the method for injection, injection, collunarium, eye drip, infiltration, absorption, physics or chemistry mediation; Or mixed by other materials or wrap up the back and import body.
The present invention now is being applied to modify its tert-butyl amine base side chain part-structure, the new compound that obtains on the clinical medicine naphthoquine phosphate basis.Prove that by the test of pesticide effectiveness compound provided by the invention has better antimalarial active.
Description of drawings
Fig. 1 is the nucleus magnetic hydrogen spectrum figure of compound 1 in the table 1.
Fig. 2 is the nucleus magnetic hydrogen spectrum figure of compound 2 in the table 1.
Fig. 3 is the nucleus magnetic hydrogen spectrum figure of compound 3 in the table 1.
Fig. 4 is the nucleus magnetic hydrogen spectrum figure of compound 4 in the table 1.
Fig. 5 is the nucleus magnetic hydrogen spectrum figure of compound 5 in the table 1.
Fig. 6 is the nucleus magnetic hydrogen spectrum figure of compound 6 in the table 1.
Fig. 7 is the nucleus magnetic hydrogen spectrum figure of compound 7 in the table 1.
Fig. 8 is the nucleus magnetic hydrogen spectrum figure of compound 8 in the table 1.
Fig. 9 is the nucleus magnetic hydrogen spectrum figure of compound 9 in the table 1.
Embodiment
The present invention will be described below by specific embodiment, but the present invention is not limited thereto.
Experimental technique described in the following embodiment if no special instructions, is ordinary method; Described reagent and biomaterial if no special instructions, all can obtain from commercial channels.
Step 1: get naphthyl alcohol 2g and be dissolved in the 40ml 7.8%NaOH aqueous solution, reacting by heating liquid to 90～95 ℃, controlled temperature also adds Ni-Al alloy 13g, question response fully after, the filtered while hot reaction solution adds hydrochloric acid after reducing to room temperature, transfers to pH=3～4.Use ethyl acetate extraction, evaporate to dryness with 60-90 ℃ of recrystallization of sherwood oil, filters, and drying gets 5,6,7,8-tetrahydrochysene-naphthyl alcohol, the 1.61g that weighs, productive rate 80%.
Step 2: get Sodium sulfanilate 2.64g heating and be dissolved in the distilled water, reaction solution is placed cold-trap, after waiting to separate out white crystal, add 1.02gNaNO
2The aqueous solution, 0～5 ℃ of controlled temperature drips 4.5ml hydrochloric acid, and after being added dropwise to complete, it is standby to continue to stir 30min.Get 5,6,7,8-tetrahydrochysene-naphthyl alcohol 2g is dissolved in the 17ml 17.4%NaOH solution, 0～5 ℃ of controlled temperature drips the above diazonium salt solution for preparing, after being added dropwise to complete, and stirring at room 1h, when being heated to 50～60 ℃, the powder 7g that takes a policy rapidly stops heating when being heated to 70 ℃, after stirring 2h under the room temperature, filter filter residue hydrochloric acid: water (2: 1, v/v) dissolving is filtered, and filter residue is used anhydrous alcohol solution again, filter, merging filtrate, evaporate to dryness promptly get formula II compound.
Step 3: 1.5g is dissolved in the 10ml distilled water with formula II compound, heating for dissolving; 1.5g is dissolved in the 10ml dehydrated alcohol heating for dissolving with formula III compound (4, the 7-dichloroquinoline).Merge two kinds of solution, add a small amount of tin protochloride, reflux 6～8h.Reacting liquor while hot is filtered, and filter residue washes repeatedly with distilled water and dehydrated alcohol.Filter residue is put in reflux 10min in 20% ammoniacal liquor again, filters, and filter residue is washed till neutrality with distilled water, is drying to obtain formula IV compound 2g, productive rate 81%.
Step 4: formula IV compound 0.41g, formaldehyde solution 0.1ml, isobutylamine alcohol 0.3g are dissolved in and add a small amount of tin protochloride in 40ml 95% ethanol, reflux, behind the 94h, evaporate to dryness with the method separation and purification of column chromatography, gets 2-(2-hydroxy-2-methyl Propylamino)-methylene radical-4-(7-chloro-4-quinoline amino)-5,6,7,8-tetrahydrochysene-naphthyl alcohol 0.15g, productive rate 28%.
Step 5: get 2-(2-hydroxy-2-methyl Propylamino)-methylene radical-4-(7-chloro-4-quinoline amino)-5,6,7,8-tetrahydrochysene-naphthyl alcohol, be dissolved in the dehydrated alcohol, add phosphoric acid adjustment pH=3 and promptly obtain 2-(2-hydroxy-2-methyl Propylamino)-methylene radical-4-(7-chloro-4-quinoline amino)-5,6,7,8-tetrahydrochysene-naphthyl alcohol phosphoric acid salt.
The color of this compound, fusing point test result see Table I (numbering 2); Its nucleus magnetic hydrogen spectrum data, mass-spectrometric data see Table II.
The compound of numbering 3-9 only needs that the alcohol of the isobutylamine in the step 4 2-hydroxy-2-methyl propylamine is replaced with corresponding compounds and gets final product with reference to embodiment 1 preparation in the table 1.The color of compound, fusing point test result see Table I; Nucleus magnetic hydrogen spectrum data, mass-spectrometric data see Table II.
Step 1: get naphthyl alcohol 2g and be dissolved in the 40ml 7.8%NaOH aqueous solution, reacting by heating liquid to 90～95 ℃, controlled temperature also adds Ni-Al alloy 13g, question response fully after, the filtered while hot reaction solution adds hydrochloric acid after reducing to room temperature, transfers to pH=3～4.Use ethyl acetate extraction, evaporate to dryness with 60-90 ℃ of recrystallization of sherwood oil, filters, and drying gets 5,6,7,8-tetrahydrochysene-naphthyl alcohol, the 1.61g that weighs, productive rate 80%.
Step 2: get Sodium sulfanilate 2.64g heating and be dissolved in the distilled water, reaction solution is placed cold-trap, after waiting to separate out white crystal, add the 1.02gNaNO2 aqueous solution, 0～5 ℃ of controlled temperature drips 4.5ml hydrochloric acid, and after being added dropwise to complete, it is standby to continue to stir 30min.Get 5,6,7,8-tetrahydrochysene-naphthyl alcohol 2g is dissolved in the 17ml 17.4%NaOH solution, 0～5 ℃ of controlled temperature drips the above diazonium salt solution for preparing, after being added dropwise to complete, and stirring at room 1h, when being heated to 50～60 ℃, the powder 7g that takes a policy rapidly stops heating when being heated to 70 ℃, after stirring 2h under the room temperature, filter filter residue hydrochloric acid: water (2: 1, v/v) dissolving is filtered, and filter residue is used anhydrous alcohol solution again, filter, merging filtrate, evaporate to dryness had both got formula II compound.
Step 3: 1.5g is dissolved among the distilled water 10ml with formula II compound, and heating for dissolving is dissolved in formula III compound 1.5g among the dehydrated alcohol 10ml heating for dissolving.Merge solution, add a small amount of tin protochloride, reflux 6～8h.Reacting liquor while hot is filtered, and filter residue washes repeatedly with distilled water and dehydrated alcohol.Filter residue is put in reflux 10min in 20% ammoniacal liquor again, filters, and filter residue is washed till neutrality with distilled water, is drying to obtain formula IV compound 2g, productive rate 81%.
Step 4: formula IV compound 0.41g, formaldehyde solution 0.1ml, 4-methyl piperidine 0.4g are dissolved in and add a small amount of tin protochloride in 40ml 95% ethanol, reflux, behind the 10h, the refrigerator freeze overnight washes out the crystal after-filtration, and cold ethanol washes repeatedly, get 2-(4-methyl piperidine base)-methylene radical-4-(7-chloro-4-quinoline amino)-5,6,7,8-tetrahydrochysene-naphthyl alcohol 0.38g, productive rate 69%.
Step 5: get 2-(4-methyl piperidine base)-methylene radical-4-(7-chloro-4-quinoline amino)-5,6,7,8-tetrahydrochysene-naphthyl alcohol, be dissolved in the dehydrated alcohol, add phosphoric acid adjustment pH=3 and can obtain 2-(4-methyl piperidine base)-methylene radical-4-(7-chloro-4-quinoline amino)-5,6,7,8-tetrahydrochysene-naphthyl alcohol phosphoric acid salt.
The color of this compound, fusing point test result see Table I; Its nucleus magnetic hydrogen spectrum data, mass-spectrometric data see Table II.
The test of pesticide effectiveness of embodiment 3, compound
Pharmacodynamic experiment has adopted and had suppressed laboratory method in international 4 days.
Animal has adopted Switzerland to plant Kunming outbreeding system mouse, and is male, body weight 18～22g, 20 ± 2 ℃ of Animal House temperature, relative humidity 60～70%.
Bai Shi plasmodium K173 strain has been adopted in the worm strain, and (reference: the subtractive cDNA library that Bai Shi plasmodium Artemisinin resistance is relevant makes up, Bei Zhuchun, Wang Jingyan, China's parasitology and parasitic disease magazine, Jun.2004, Vol.22, No.3:139-143), can obtain from Inst. of Epidemiology and Microbiology, Academy of Military Medical Sciences, PL.
The medicine preparation: the medicine after will weighing is in mortar, compound 1 and compound 9 need to add a little tween 80 and grind, compound 2-7 can be directly with dissolved in distilled water, become isometric(al) different concns (0.125 with distilled water diluting, 0.25,0.5,1.0,2.0mg/ml) aqueous suspensions, every mouse is irritated stomach 0.2ml at every turn.
Experimental technique is that inoculation day is D
0, every decimal abdominal cavity inoculation Bai Shi plasmodium K
173Strain 10
7Individual, behind the inoculation 30min, each dosage group gastric infusion, 4 days (D of successive administration
0～D
3), D
4It gets blood, smear counting plasmodium parasitic rate, and linear regression method calculates the ED of test-compound
50And ED
90, the results are shown in Table I.
Table I compound physico-chemical property and pharmacodynamic result
Annotate: naphthoquine phosphate ED
50=0.31mg/kg; ED
90=0.89mg/kg
Table II compound nucleus magnetic hydrogen spectrum, mass spectrum and compound title
Claims (10)
1. compound shown in the formula I or its pharmacy acceptable salt:
Among the formula I, R contains 1～2 hydroxyl and has the 5-6 member heterocyclic ring containing nitrogen base that the straight or branched alkylamino radical of 3～4 carbon atoms, the straight or branched enamine base with 3 carbon atoms or alkyl replace.
2. according to the described compound of claim 1 or its pharmacy acceptable salt, it is characterized in that: described R is selected from any one in the following radicals:
3. according to claim 1 or 2 described compounds or its pharmacy acceptable salt, it is characterized in that: described pharmacy acceptable salt is phosphoric acid salt, hydrochloride, vitriol, nitrate, acetate, formate or maleate.
4. prepare the method for the described compound of claim 1, comprise the steps:
1) formula II compound and formula III compound are carried out back flow reaction in the mixed solvent of ethanol and water, obtain compound shown in the formula IV;
2) compound shown in the formula IV, formaldehyde and formula V compound are reacted in solvent, or the 5-6 member heterocyclic ring containing nitrogen compound of compound shown in the formula IV, formaldehyde and alkyl replacement is reacted in solvent, obtain compound shown in the formula I; Described solvent is the mixed solvent of ethanol or ethanol and water;
NH
2R
2
(formula V)
Among the formula V, R
2For containing 1～2 hydroxyl and having the straight or branched alkylamino radical of 3～4 carbon atoms or have the straight or branched enamine base of 3 carbon atoms.
5. method according to claim 4 is characterized in that: in the step 1), the mass ratio of described formula II compound and formula III compound is 1: (1-1.2); The volume ratio of ethanol and water is 1 in the described mixed solvent: (0.8-1.2); The time of described back flow reaction is 6-8 hour; Step 2) in, the volume ratio of ethanol and water is (85-100) in the mixed solvent of described ethanol and water: (15-0), but water is not 0; The temperature of described reaction is 60-84 ℃, and the time is 10-96 hour.
6. according to claim 4 or 5 described methods, it is characterized in that: the R among the described formula V
2Be selected from the following radicals any one:
The 5-6 member heterocyclic ring containing nitrogen compound that described alkyl replaces is the 4-methyl piperidine.
7. the method for the salt of preparation claim 1 or 2 described compounds comprises the steps: claim 1 or 2 described compounds are dissolved in the dehydrated alcohol, and to wherein adding organic acid or mineral acid reacts, obtains the salt of claim 1 or 2 described compounds.
8. each described compound or its pharmacy acceptable salt prevent and/or treat application in the malaria medicine in preparation among the claim 1-3.
9. medicine that prevents and/or treats malaria, its activeconstituents is each described compound or its pharmacy acceptable salt among the claim 1-3.
10. a pharmaceutical composition that prevents and/or treats malaria comprises each described compound or its pharmacy acceptable salt among the claim 1-3, and pharmaceutically acceptable carrier.
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| CN2011101008986A CN102229564A (en) | 2011-04-21 | 2011-04-21 | 4-(7-chlorine-4aminoquinoline)-5,6,7,8-tetrahydro-alpha-naphthol derivatives, preparation method and application thereof |
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| CN2011101008986A CN102229564A (en) | 2011-04-21 | 2011-04-21 | 4-(7-chlorine-4aminoquinoline)-5,6,7,8-tetrahydro-alpha-naphthol derivatives, preparation method and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232444A (en) * | 2013-04-18 | 2013-08-07 | 中国人民解放军军事医学科学院微生物流行病研究所 | Naphthoquine derivatives, and preparation and application thereof |
| CN105085505A (en) * | 2014-05-07 | 2015-11-25 | 昆明制药集团股份有限公司 | Novel preparation process for naphthoquine salt |
| CN111265527A (en) * | 2020-03-05 | 2020-06-12 | 中国人民解放军军事科学院军事医学研究院 | Application of naphthoquine and pharmaceutically acceptable salt thereof in preparation of anti-coronavirus medicines |
| CN112409254A (en) * | 2020-12-08 | 2021-02-26 | 重庆康乐制药有限公司 | Preparation method of naphthoquine phosphate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3948920A (en) * | 1971-10-19 | 1976-04-06 | Aktiebolaget Astra | New anti-malarial agents |
| CN1093356A (en) * | 1993-04-06 | 1994-10-12 | 中国人民解放军军事医学科学院微生物流行病研究所 | The preparation method of naphthol quinic salts |
-
2011
- 2011-04-21 CN CN2011101008986A patent/CN102229564A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3948920A (en) * | 1971-10-19 | 1976-04-06 | Aktiebolaget Astra | New anti-malarial agents |
| CN1093356A (en) * | 1993-04-06 | 1994-10-12 | 中国人民解放军军事医学科学院微生物流行病研究所 | The preparation method of naphthol quinic salts |
Non-Patent Citations (2)
| Title |
|---|
| 《J.Med.Chem.》 19871231 Stephen J. Kesten,et al. Synthesis and Antimalarial Effects of 4-[( 7-Chloro-4-quinolinyl)amino]-2-[diethy1amino)methyl]-6-alkylphenols and Their N-Oxides 906-911 1-10 第30卷, 第5期 * |
| 《医药工业》 19851231 张洪北等 2-二烷氨甲基-4-杂环氨基-5,6,7,8-四氢萘酚衍生物的合成及抗疟活性 8(56)-12(60) 1-10 第16卷, 第2期 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232444A (en) * | 2013-04-18 | 2013-08-07 | 中国人民解放军军事医学科学院微生物流行病研究所 | Naphthoquine derivatives, and preparation and application thereof |
| CN103232444B (en) * | 2013-04-18 | 2015-07-22 | 中国人民解放军军事医学科学院微生物流行病研究所 | Naphthoquine derivatives, and preparation and application thereof |
| CN105085505A (en) * | 2014-05-07 | 2015-11-25 | 昆明制药集团股份有限公司 | Novel preparation process for naphthoquine salt |
| CN105085505B (en) * | 2014-05-07 | 2018-03-13 | 昆药集团股份有限公司 | A kind of naphthol quinic salts new preparation process |
| CN111265527A (en) * | 2020-03-05 | 2020-06-12 | 中国人民解放军军事科学院军事医学研究院 | Application of naphthoquine and pharmaceutically acceptable salt thereof in preparation of anti-coronavirus medicines |
| CN112409254A (en) * | 2020-12-08 | 2021-02-26 | 重庆康乐制药有限公司 | Preparation method of naphthoquine phosphate |
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