JPS5951941B2 - carbostyril derivatives - Google Patents
carbostyril derivativesInfo
- Publication number
- JPS5951941B2 JPS5951941B2 JP52097185A JP9718577A JPS5951941B2 JP S5951941 B2 JPS5951941 B2 JP S5951941B2 JP 52097185 A JP52097185 A JP 52097185A JP 9718577 A JP9718577 A JP 9718577A JP S5951941 B2 JPS5951941 B2 JP S5951941B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- reaction
- sodium
- carbostyril derivatives
- production example
- 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
Links
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000005606 carbostyryl group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000007686 potassium Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- -1 sodium and potassium Chemical compound 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Description
【発明の詳細な説明】 本発明は新規なカルボスチリル誘導体に関する。[Detailed description of the invention] The present invention relates to novel carbostyril derivatives.
本発明の化合物は新規化合物であり、一般式〔式中Ｒは
低級アルキル基を、Ｘはハロゲン原子を、カルボス千リ
ル骨格の３、４位の結合は一重結合又は二重結合を示す
。The compound of the present invention is a novel compound, and has the general formula [wherein R represents a lower alkyl group, X represents a halogen atom, and the bonds at the 3rd and 4th positions of the carbosthylyl skeleton represent a single bond or a double bond.
〕で表わされる。該化合物は血小板凝集抑制作用、消炎
作用、血液中の脂質含有量特にコレステロール、ホスホ
リピド、トリグリセリド等の含有量を低下させる作用を
有し、血栓予防薬、消炎剤、動脈硬化症の治療及び予防
薬等として有用である。上記一般式〔１〕に於てＲで示
される低級アルキル基としては炭素数１〜４の直鎖もし
くは分枝状のアルキル基を挙げることができ、具体的に
はメチル、エチル、プロピル、イソプロピル、ブチル、
ｓｅｃ−ブチル基等を例示できる。]. The compound has platelet aggregation inhibiting action, anti-inflammatory action, and action of lowering the lipid content in the blood, especially the content of cholesterol, phospholipids, triglycerides, etc., and is used as a blood clot preventive agent, an anti-inflammatory agent, and an agent for treating and preventing arteriosclerosis. It is useful as such. The lower alkyl group represented by R in the above general formula [1] can include straight chain or branched alkyl groups having 1 to 4 carbon atoms, specifically methyl, ethyl, propyl, isopropyl. , butyl,
Examples include sec-butyl group.
またＸで示されるハロゲン原子としては具体的には塩素
原子、臭素原子、沃素原子及び弗素原子を挙げることが
できる。本発明化合物のうち代表的なものを以下に掲げ
る。Further, specific examples of the halogen atom represented by X include a chlorine atom, a bromine atom, an iodine atom, and a fluorine atom. Representative compounds of the present invention are listed below.
６−（３−エトキシカルボニルプロポキシ）−７−フロ
モー ３、４−ジヒドロカルボス千リル６−（３−ｓｅ
ｃ−ブトキシカルボニルプロポキシ）−７−フロモー
３、４−ジヒドロカルボスチリル６−（３−エトキシカ
ルボニルプロボキシ）−７−クロルカルボスチリル６−
（３−プロポキシカルボニルプロポキシ）一７−フロモ
ー ３、４−ジヒドロカルボス千リル６−（３−メトキ
シカルボニルプロポキシ）−７−クロルカルボス千リル
６−（３−ィソプロポキシカルボニルプロボキシ）−７
−フロロカルボスチリル本発明の化合物は橿々の方法で
製造されるが、その好ましい一例としては例えば下式に
示す如く一般式〔〕で表わされる公知のヒドロキシカル
ボスチリル誘導体に一般式〔〕で表わされる公知の〔ハ
ロゲノエステル誘導体を脱ハロゲン化水素反応させて製
造される。6-(3-ethoxycarbonylpropoxy)-7-furomo 3,4-dihydrocarbosthuryl 6-(3-se
c-butoxycarbonylpropoxy)-7-furomo
3,4-dihydrocarbostyryl 6-(3-ethoxycarbonylproboxy)-7-chlorocarbostyryl 6-
(3-propoxycarbonylpropoxy)-7-furomo 3,4-dihydrocarbosenyl 6-(3-methoxycarbonylpropoxy)-7-chlorocarbosenyl 6-(3-isopropoxycarbonylproboxy)-7
-Fluorocarbostyril The compound of the present invention can be produced by various methods, and a preferred example thereof is, for example, as shown in the following formula: It is produced by dehydrohalogenating a known halogenoester derivative.
（上式に於て、Ｘ１はハロゲン原子を示す。(In the above formula, X1 represents a halogen atom.
Ｒ及びＸは前記に同じ。）この脱ハロゲン化水素反応は
塩基性化合物を説ハロゲン化水素剤として用いて行なわ
れる０塩基性化合物としては公知のものを広く使用でき
、たとえば、水酸化ナトリウム、水酸化カリウム、炭酸
ナトリウム、炭酸カリウム、炭酸水素ナトリウム、炭酸
水素カリウム、炭酸銀などの無機塩基、ナトリウム、カ
リウムなどのアルカリ金属、ナトリウムメチラート、ナ
トリウムエチラートなどのアルコラード、トリエチルア
ミン、ピリジン、Ｎ，Ｎ−ジメチルアニリンなどの有機
塩基が挙げられる。R and X are the same as above. ) This dehydrohalogenation reaction is carried out using a basic compound as a hydrogen halide agent. A wide variety of known zero-basic compounds can be used, such as sodium hydroxide, potassium hydroxide, sodium carbonate, carbonate, etc. Inorganic bases such as potassium, sodium bicarbonate, potassium bicarbonate, silver carbonate, alkali metals such as sodium and potassium, alcoholades such as sodium methylate and sodium ethylate, organic bases such as triethylamine, pyridine, N,N-dimethylaniline, etc. can be mentioned.
該反応は無溶媒でもあるいは溶媒の存在下でも行なわれ
、溶媒としては反応に悪影響を与えない不活性のものが
すべて用いられ、たとえばメタノール、エタノール、プ
ロパノール、ブタノール、エチレングリコールなどのア
ルコール類、ジメチルエーテル、テトラヒドロフラン、
ジオキサン、モノグライム、ジグライムなどのエーテル
類、アセトン、メチルエチルケトンなどのケトン類、ベ
ンゼン、トルエン、キシレンなどの芳香族炭化水素類、
酢酸メチル、酢酸エチルなどのエステル類、Ｎ，Ｎ−ジ
メチルホルムアミド、ジメチルスルホキサイド、ヘキサ
メチルリン酸トリアミドなどの非プロトン性極性溶媒な
どが挙げられる。また該反応は沃化ナトリウム、沃化カ
リウムなどの金属沃化物の存在下に行なうのが有利であ
る。上記方法におけるヒドロキシカルボスチリル誘導体
〔〕とハロゲノエステル誘導体〔〕との使用割合はとく
に限定されず、広範囲の中から遺宜に選択されるが、通
常、前者に対して後者を等モル〜５倍モル、好ましくは
等モル〜２倍モル量にて用いるのが望ましい。The reaction is carried out without a solvent or in the presence of a solvent, and all inert solvents that do not adversely affect the reaction are used, such as alcohols such as methanol, ethanol, propanol, butanol, and ethylene glycol, and dimethyl ether. , tetrahydrofuran,
Ethers such as dioxane, monoglyme, and diglyme, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene, toluene, and xylene,
Examples include esters such as methyl acetate and ethyl acetate, aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric triamide. Further, the reaction is advantageously carried out in the presence of a metal iodide such as sodium iodide or potassium iodide. The ratio of the hydroxycarbostyryl derivative [] and the halogenoester derivative [] used in the above method is not particularly limited and may be selected from a wide range, but usually the latter is equal to or 5 times the amount of the former. It is desirable to use it in a molar amount, preferably in an equimolar to twice molar amount.
また、その反応温度もとくに限定されないが、通常、室
温〜２００℃、好ましくは５０〜１５０℃で行なわれる
。反応時間は通常１〜３０・時間、好ましくは１〜１５
時間であるＯ斯くして得られる本発明化合物は抽出、再
結晶、カラムクロマトグラフイ一、プリパラテイブ薄層
クロマトグラフイ一等の慣用手段により分離、精製され
る。Further, the reaction temperature is not particularly limited, but it is usually carried out at room temperature to 200°C, preferably 50 to 150°C. The reaction time is usually 1 to 30 hours, preferably 1 to 15 hours.
The compound of the present invention thus obtained is separated and purified by conventional means such as extraction, recrystallization, column chromatography, preparative thin layer chromatography, etc.
更に本発明化合物は下式に示す如く一般式〔〕で表わさ
れる公知のカルボスチリル誘導体を公知のハロゲン化剤
でハロゲン化することによつても製造される。Furthermore, the compound of the present invention can also be produced by halogenating a known carbostyryl derivative represented by the general formula [ ] with a known halogenating agent as shown below.
本発明化合物の製造例を以下に掲げる。Production examples of the compounds of the present invention are listed below.
製造例 １
ジメチルホルムアミド５０−に７ープロモ一６−ヒドロ
キシ−３，４−ジヒドロカルボス千リル２．４３ｆ！、
エチル−γ−ブロモブチレート２．３５ｙ及び炭酸カリ
ウム１．６５９を加えて６０〜７０℃にて３時間攪拌す
る。Production Example 1 2.43 f of 7-promo-6-hydroxy-3,4-dihydrocarbos thuryl in 50-dimethylformamide! ,
Add 2.35 y of ethyl-γ-bromobutyrate and 1.659 y of potassium carbonate, and stir at 60 to 70°C for 3 hours.
冷後反応液を飽和食塩水３００ｍ１に注ぎ、析出晶を戸
取し水洗する。得られた粗結晶を酢酸エチルから再結晶
して無色無定形晶の６−（３−エトキシカルボニルプロ
ポキシ）ーJメ[プロモ一３，４−ジヒドロカルボスチリ
ル２，９９を得る。融点１４５〜１４７℃
製造例 ２
製造例１と同様にして６−（３−エトキシカルボニルプ
ロポキシ）−Jメ[プロモカルボスチリルを得る。After cooling, the reaction solution was poured into 300 ml of saturated brine, and the precipitated crystals were taken out and washed with water. The obtained crude crystals are recrystallized from ethyl acetate to obtain colorless amorphous crystals of 6-(3-ethoxycarbonylpropoxy)-J-promo-3,4-dihydrocarbostyryl 2,99. Melting point: 145-147°C Production Example 2 In the same manner as in Production Example 1, 6-(3-ethoxycarbonylpropoxy)-J-promocarbostyryl is obtained.
無色板状晶（再結晶溶媒：メタノール）、融点１８２．
５〜１８４℃。製造例 ３
製造例１と同様にして６−（３−プロポキシカルボニル
プロポキシ）−Jメ[プロモ一３，４−ジヒドロカルボス
チリルを得る。Colorless plate crystals (recrystallization solvent: methanol), melting point 182.
5-184℃. Production Example 3 In the same manner as in Production Example 1, 6-(3-propoxycarbonylpropoxy)-J-promo-3,4-dihydrocarbostyryl is obtained.
無色無定形晶（再結晶溶媒：エタノール）、融点１３６
〜１３７．５℃製造例 ４クロロホルム７０ＴＩＬＩに
６−（３−エトキシカルボニルプロポキシ）−３，４−
ジヒドロカルボスチリル２．７７９を加えて溶解させ、
３５〜４５℃に保ちつつ攪拌下臭素１．６ｆ！を含むク
ロロホルム１０ｍ１溶液を７５分を要して滴下する。Colorless amorphous crystal (recrystallization solvent: ethanol), melting point 136
~137.5℃ Production example 4 Chloroform 70TILI to 6-(3-ethoxycarbonylpropoxy)-3,4-
Add and dissolve 2.779 dihydrocarbostyril,
Bromine 1.6f while stirring while keeping at 35~45℃! A solution of 10 ml of chloroform containing the solution was added dropwise over a period of 75 minutes.
Claims (1)
ルボスチリル骨格の３，４位の結合は一重結合又は二重
結合を示す。 〕で表わされるカルボスチリル誘導体。[Claims] 1 General formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, R is a lower alkyl group, Indicates a double bond. ] A carbostyryl derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52097185A JPS5951941B2 (en) | 1977-08-12 | 1977-08-12 | carbostyril derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52097185A JPS5951941B2 (en) | 1977-08-12 | 1977-08-12 | carbostyril derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5432481A JPS5432481A (en) | 1979-03-09 |
| JPS5951941B2 true JPS5951941B2 (en) | 1984-12-17 |
Family
ID=14185514
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52097185A Expired JPS5951941B2 (en) | 1977-08-12 | 1977-08-12 | carbostyril derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5951941B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58131571A (en) * | 1982-01-14 | 1983-08-05 | Victor Co Of Japan Ltd | Detection of speed of hall motor |
| DE102008022221A1 (en) | 2008-05-06 | 2009-11-12 | Universität des Saarlandes | Inhibitors of human aldosterone synthase CYP11B2 |
| US8541404B2 (en) | 2009-11-09 | 2013-09-24 | Elexopharm Gmbh | Inhibitors of the human aldosterone synthase CYP11B2 |
-
1977
- 1977-08-12 JP JP52097185A patent/JPS5951941B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5432481A (en) | 1979-03-09 |
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