JPH08805B2 - New oxide derivative of NN-dimethylethylamine, method for producing the same, and pharmaceutical composition containing the same - Google Patents
New oxide derivative of NN-dimethylethylamine, method for producing the same, and pharmaceutical composition containing the sameInfo
- Publication number
- JPH08805B2 JPH08805B2 JP61246468A JP24646886A JPH08805B2 JP H08805 B2 JPH08805 B2 JP H08805B2 JP 61246468 A JP61246468 A JP 61246468A JP 24646886 A JP24646886 A JP 24646886A JP H08805 B2 JPH08805 B2 JP H08805B2
- Authority
- JP
- Japan
- Prior art keywords
- dimethylethylamine
- pharmaceutical composition
- same
- bisphenoxy
- producing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 150000003839 salts Chemical class 0.000 claims description 8
- QNMGHBMGNRQPNL-UHFFFAOYSA-N medifoxamine Chemical compound C=1C=CC=CC=1OC(CN(C)C)OC1=CC=CC=C1 QNMGHBMGNRQPNL-UHFFFAOYSA-N 0.000 claims description 7
- 150000001204 N-oxides Chemical class 0.000 claims description 5
- -1 inorganic acid salt Chemical class 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000001430 anti-depressive effect Effects 0.000 claims description 3
- 239000000935 antidepressant agent Substances 0.000 claims description 3
- 229940005513 antidepressants Drugs 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001451 organic peroxides Chemical class 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002631 hypothermal effect Effects 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 208000020401 Depressive disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960003123 medifoxamine Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- LOEMDEDKAHXRTN-UHFFFAOYSA-N 2-nitrobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1[N+]([O-])=O LOEMDEDKAHXRTN-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000005997 Calcium carbide Substances 0.000 description 1
- 208000027776 Extrapyramidal disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000012826 adjustment disease Diseases 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 208000018300 basal ganglia disease Diseases 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229940100242 glycol stearate Drugs 0.000 description 1
- GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical class O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- CLZWAWBPWVRRGI-UHFFFAOYSA-N tert-butyl 2-[2-[2-[2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-5-bromophenoxy]ethoxy]-4-methyl-n-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]anilino]acetate Chemical compound CC1=CC=C(N(CC(=O)OC(C)(C)C)CC(=O)OC(C)(C)C)C(OCCOC=2C(=CC=C(Br)C=2)N(CC(=O)OC(C)(C)C)CC(=O)OC(C)(C)C)=C1 CLZWAWBPWVRRGI-UHFFFAOYSA-N 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229960000317 yohimbine Drugs 0.000 description 1
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C291/00—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00
- C07C291/02—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds
- C07C291/04—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds containing amino-oxide bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 本発明はNN−ジメチルエチルアミンの新規な誘導体、
特にＮ−オキシドに関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention is a novel derivative of NN-dimethylethylamine,
In particular, it relates to N-oxide.
本発明は殊に、下記の式で表わされる2,2−ビスフェ
ノキシNN−ジメチルエチルアミンＮ−オキシドに関す
る。The invention particularly relates to 2,2-bisphenoxy NN-dimethylethylamine N-oxides of the formula:
本発明はまた、無機または有機酸、特にクロルヒドレ
ート、臭化ヒドレート、硫酸塩のような強酸と付加反応
したＮ−オキシドの塩に関する。 The invention also relates to salts of N-oxides which have been addition reacted with inorganic or organic acids, especially strong acids such as chlorohydrates, bromide hydrates, sulphates.
Ｎ−酸化2,2−ビスフェノキシNN−ジメチルエチルア
ミンは弱塩基であり、本質的には非還元性の強酸との塩
をもたらす。N-oxidized 2,2-bisphenoxy NN-dimethylethylamine is a weak base, providing salts with strong acids which are essentially non-reducing.
本発明に従う上記化合物は、2,2−ビスフェノキシNN
−ジメチルエチルアミンまたはその塩の１つに不活性溶
媒中で無機または有機過酸化物を作用させる方法により
生成される。この過酸化物はパーハイドロールであるこ
とが望ましい。これはまた、過酸化ターブチル等の過酸
化水素アルカノル、過酸化ヘキサフルオロアセトン等の
過酸化セトン、p.ニトロ過安息香酸またはＮ−塩化過安
息香酸等の過酸でもよい。The above compound according to the invention is 2,2-bisphenoxy NN
-Produced by the method of reacting dimethylethylamine or one of its salts with an inorganic or organic peroxide in an inert solvent. This peroxide is preferably perhydrol. It may also be a hydrogen peroxide alkanol such as terbutyl peroxide, a cetone peroxide such as hexafluoroacetone peroxide, a peracid such as p. Nitroperbenzoic acid or N-chloroperbenzoic acid.
反応媒質の溶媒はメタノール、エタノール等の不活性
溶媒、トルエンやキシレン等の芳香族炭化水素、あるい
はジメチルホルムアミドやジメチルアセトアミド等のNN
−２置換基アミドである。The solvent of the reaction medium is an inert solvent such as methanol or ethanol, an aromatic hydrocarbon such as toluene or xylene, or an NN such as dimethylformamide or dimethylacetamide.
-2 substituent amide.
2,2−ビスフェノキシNN−ジメチルエチルアミンＮ−
オキシドおよびその塩には、抗うつ薬としての性質があ
り（従来の薬物試験による）、レセルピンやアポモルヒ
ネの低体温化効果を抑制し、キオヒンビンの注入によっ
て誘発された集団致死量を高め、マウスを用いた極限試
験におけるマウスの絶望度を中和する。2,2-Bisphenoxy NN-Dimethylethylamine N-
Oxides and their salts have antidepressant properties (according to conventional drug tests), suppress the hypothermic effect of reserpine and apomorphine, increase the mass lethality induced by injection of chiohimbine, Neutralize the despair of mice in the limit test used.
抗うつ薬としての性質を備えているため、うつ状態、
退行期精神病、躁うつ状態、心因性や反応性うつ病の治
療の目的で人や動物の治療に用いられる。この化合物
は、毒性がほとんど無いため、治療の安全域は非常に大
きく、三環タイプの抗うつ薬との併用で現われる副作用
（口の乾燥、錐体外路障害）の心配なしに投与すること
ができる。Depressive state because of its properties as an antidepressant,
Used in the treatment of humans and animals for the treatment of regressive psychosis, manic depressive states, psychogenic and reactive depression. Since this compound has almost no toxicity, the safety margin of treatment is very large, and it can be administered without worrying about the side effects (dry mouth, extrapyramidal disorder) that appear in combination with tricyclic antidepressants. it can.
2,2−ビスフェノキシNN−ジメチルエチルアミンＮ−
オキシドの服用量は、患者の体重や年齢、治療上の注意
点、病状の継続期間、投与方法等に応じて大きく異な
る。2,2-Bisphenoxy NN-Dimethylethylamine N-
The dose of oxide varies greatly depending on the weight and age of the patient, precautions for treatment, duration of medical condition, administration method, and the like.
服用量は大人で１回につき0.05〜0.500gの間、１日に
つき0.1〜0.5gの間である。The dose is between 0.05 and 0.500 g per adult and between 0.1 and 0.5 g per day.
治療用の薬の投与の目的で、2,2−ビスフェノキシNN
−ジメチルアミンＮ−オキシドまたはその付加化合塩
は、薬剤組成物に調製される。この薬剤組成物は、薬理
学上受容されている無害で、不活性な賦形剤に配合また
は混合された形で上記Ｎ−オキシドあるいはその塩の一
つを含む。2,2-bisphenoxy NN for the purpose of administration of therapeutic drugs
-Dimethylamine N-oxide or its addition salt combination is prepared into a pharmaceutical composition. This pharmaceutical composition comprises one of the above-mentioned N-oxides or salts thereof in the form of being mixed or mixed with a pharmacologically acceptable, harmless and inert excipient.
不活性な賦形剤は非経口、或いは、口腔、直腸、皮膚
を通じて投与するのに適するものである。例を挙げるな
ら、処理済または未処理の澱粉、セルロース、Ｏ−アル
キル化セルロース、炭化カルシウム、ステアリン酸マグ
ネシウムまたはタルク、水または生理食塩水、カカオバ
ターまたはステアリン酸ポリエチレングリコール、ベン
ジルアルコールまたはジメチルスルホキシド等の極性溶
媒がある。Inert excipients are those suitable for parenteral or buccal, rectal, and dermal administration. Examples include treated or untreated starch, cellulose, O-alkylated cellulose, calcium carbide, magnesium stearate or talc, water or saline, cocoa butter or polyethylene glycol stearate, benzyl alcohol or dimethyl sulfoxide. There are polar solvents.
薬剤組成物の調製は製薬技術における従来法に従って
行われる。特に、外被に包まれたあるいは包まれていな
い錠剤、糖衣錠剤、ゼラチン質のカプセル、カプセル、
点滴薬、注射用または飲み薬用溶液、座薬、経皮用溶液
の形態にすることができる。Preparation of the pharmaceutical composition is carried out according to conventional methods in the pharmaceutical art. In particular, tablets, sugar-coated tablets, gelatin capsules, capsules, with or without envelopes,
It can be in the form of drops, injectable or swallowable solutions, suppositories, transdermal solutions.
実施例 以下、本発明の実施例を示すが、本発明はこれに限定
されるものではない。Examples Hereinafter, examples of the present invention will be shown, but the present invention is not limited thereto.
実施例１ 2,2−ビスフェノキシNN−ジメチルエチルアミンＮ−
オキシドの製造。Example 1 2,2-Bisphenoxy NN-Dimethylethylamine N-
Oxide production.
臭素の入ったアンプル、温度計、冷却装置を備え、メ
タノール50ml中にNN−ジメチル−2,2ジフェノキシエタ
ンアミン5.15g（0.02M）を含む100mlのトリコールに、3
0％の過酸化水素水6mlを１滴ずつ加える。室温で30分間
撹拌した後、35℃に暖め、12時間この温度に保つ。Equipped with an ampoule containing bromine, a thermometer, and a cooling device, 100 ml of Tricol containing 5.15 g (0.02 M) of NN-dimethyl-2,2 diphenoxyethanamine in 50 ml of methanol was added to
Add 6 ml of 0% hydrogen peroxide drop by drop. After stirring for 30 minutes at room temperature, warm to 35 ° C and keep at this temperature for 12 hours.
メタノールは蒸発し、水はエタノールとの共沸混合物
として除去される。得られた油はエーテルに取り戻さ
れ、白色の固体が生成される。ろ化と乾燥の後、104℃
で融解するNN−ジメチル−2,2−ジフェノキシエタンア
ミンＮ−オキシド3.08gが得られる。Methanol evaporates and water is removed as an azeotrope with ethanol. The resulting oil is reconstituted in ether to produce a white solid. 104 ° C after filtering and drying
3.08 g of NN-dimethyl-2,2-diphenoxyethanamine N-oxide, which melts at.
収率:56.5％ Rf:0.14CHCL3/CH3OH 9/1 核磁気共鳴：（CDCl3）10H（m;6.8−7.3）;1H（t;6.
7）;2H（d;3.7）;6H（s;3.2） 核磁気共鳴（メジフォクスアミン）：（CDCl3）10H（m;
6.8−7.3）;1H（t;5.8）;2H（d;2.8）;6H（s;2.32） 実施例II 下記の通常の薬理試験１）〜５）を行って、本発明の
Ｎ−酸化2,2−ビスフェノキシＮ、Ｎ−ジメチルエチル
アミンと、2,2−ビズフェノキシＮ、Ｎ−ジメチルエチ
ルアミン（メジフォクスアミン）とを比較した。 Yield: 56.5% Rf: 0.14CHCL 3 / CH 3 OH 9/1 NMR: (CDCl 3) 10H (m ; 6.8-7.3); 1H (t; 6.
7); 2H (d; 3.7); 6H (s; 3.2) Nuclear Magnetic Resonance (Medifoxamine): (CDCl 3 ) 10H (m;
6.8-7.3); 1H (t; 5.8); 2H (d; 2.8); 6H (s; 2.32) Example II The following usual pharmacological tests 1) to 5) were carried out to carry out the N-oxidation 2 of the present invention. 2,2-Bisphenoxy N, N-dimethylethylamine was compared with 2,2-bisphenoxy N, N-dimethylethylamine (medifoxamine).
１） 急性致死量試験。1) Acute lethal dose test.
２） レセルピン（Resperpine）をマウスに注射（100m
g/kg）した低温症試験。2) Resperpine was injected into mice (100m
g / kg) hypothermia test.
３） アボモルヒネをマウスに注射（50mg/kg、100mg/k
g）した低温症試験。3) Avomorphine was injected into mice (50mg / kg, 100mg / k
g) The hypothermia test.
４） ヨヒンビンをマウスに投与した時の毒性試験。4) Toxicity test when yohimbine was administered to mice.
５） マウスの絶望水泳試験。5) Despaired swimming test in mice.
結果は下記の表に示す。 The results are shown in the table below.
Claims (6)
フェキシＮ、Ｎ−ジメチルエチルアミン： 1. N-oxidized 2,2-bisphenoxy N, N-dimethylethylamine represented by the following formula:
の無機酸塩または有機酸塩。2. An inorganic acid salt or an organic acid salt of the N-oxide according to claim 1.
ルアミンまたはその塩を不活性溶媒中で無機または有機
過酸化物と反応させることを特徴とする下記の式で表わ
されるＮ−酸化2,2−ビスフェキシＮ、Ｎ−ジメチルエ
チルアミンの製造方法： 3. N-Oxide 2, represented by the following formula, which comprises reacting 2,2-bisphenoxy N, N-dimethylethylamine or a salt thereof with an inorganic or organic peroxide in an inert solvent. Method for producing 2-bisfoxy N, N-dimethylethylamine:
チルエチルアミンまたはその塩を有効量だけ薬理学上許
容される無毒で不活性な賦形剤と混合または配合したこ
とを特徴とする抗抑うつ病治療用医薬組成物。4. The following formula as an active ingredient: An antidepressant characterized by mixing or blending an effective amount of N-oxidized 2,2-bisphenoxy N, N-dimethylethylamine or a salt thereof represented by the following with a pharmacologically acceptable non-toxic and inactive excipient A pharmaceutical composition for treating a disease.
適した賦形剤である特許請求の範囲第４項に記載の医薬
組成物。5. The pharmaceutical composition according to claim 4, which is an excipient suitable for enteral, oral, rectal or transdermal administration.
gの間にある特許請求の範囲第４または５項に記載の医
薬組成物。6. An effective amount of 0.05g to 0.500 per dose
The pharmaceutical composition according to claim 4 or 5, which lies between g.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8515448A FR2588552B3 (en) | 1985-10-16 | 1985-10-16 | NOVEL OXIDE DERIVATIVE OF NN-DIMETHYL ETHYLAMINE, PROCESS FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
| FR8515448 | 1985-10-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6293269A JPS6293269A (en) | 1987-04-28 |
| JPH08805B2 true JPH08805B2 (en) | 1996-01-10 |
Family
ID=9323943
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61246468A Expired - Fee Related JPH08805B2 (en) | 1985-10-16 | 1986-10-16 | New oxide derivative of NN-dimethylethylamine, method for producing the same, and pharmaceutical composition containing the same |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPH08805B2 (en) |
| FR (1) | FR2588552B3 (en) |
-
1985
- 1985-10-16 FR FR8515448A patent/FR2588552B3/en not_active Expired
-
1986
- 1986-10-16 JP JP61246468A patent/JPH08805B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6293269A (en) | 1987-04-28 |
| FR2588552B3 (en) | 1987-12-31 |
| FR2588552A1 (en) | 1987-04-17 |
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|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |