JPS601184A - Furoindole compound - Google Patents
Furoindole compoundInfo
- Publication number
- JPS601184A JPS601184A JP58108230A JP10823083A JPS601184A JP S601184 A JPS601184 A JP S601184A JP 58108230 A JP58108230 A JP 58108230A JP 10823083 A JP10823083 A JP 10823083A JP S601184 A JPS601184 A JP S601184A
- Authority
- JP
- Japan
- Prior art keywords
- indole
- furo
- trifluoromethyl
- compound
- morpholinocarbonyl
- 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.)
- Pending
Links
- -1 Furoindole compound Chemical class 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 9
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 9
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 abstract description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract description 8
- 239000002253 acid Substances 0.000 abstract description 5
- 230000000202 analgesic effect Effects 0.000 abstract description 5
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
- 150000004820 halides Chemical class 0.000 abstract description 4
- 125000005843 halogen group Chemical group 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 2
- VEYWHOMQFPXREZ-UHFFFAOYSA-N morpholin-4-yl-[6-(trifluoromethyl)-4h-furo[3,2-b]indol-2-yl]methanone Chemical compound C=1C(C(F)(F)F)=CC=C(C=2O3)C=1NC=2C=C3C(=O)N1CCOCC1 VEYWHOMQFPXREZ-UHFFFAOYSA-N 0.000 abstract description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229940113118 carrageenan Drugs 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 239000012954 diazonium Substances 0.000 description 3
- 150000001989 diazonium salts Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- QQXQAEWRSVZPJM-UHFFFAOYSA-N ethyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1 QQXQAEWRSVZPJM-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- GUMVEYKDOAQLGN-UHFFFAOYSA-N 1h-indole-2-carbonyl chloride Chemical compound C1=CC=C2NC(C(=O)Cl)=CC2=C1 GUMVEYKDOAQLGN-UHFFFAOYSA-N 0.000 description 1
- HCUARRIEZVDMPT-UHFFFAOYSA-M 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)[O-])=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-M 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- ATXBGHLILIABGX-UHFFFAOYSA-N 2-nitro-4-(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O ATXBGHLILIABGX-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は鎮痛作用および抗炎症作用を有する新規な７０
インド一ル化合物に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention discloses a novel 70-glycerin compound having analgesic and anti-inflammatory effects.
Concerning indyl compounds.
さらに詳しくは、本発明は一般式
％式％
（式中、Ｒはアルキル基を示す）で表わされるフロイン
ドール化合物である。More specifically, the present invention is a Freundole compound represented by the general formula % (wherein R represents an alkyl group).
一般式１で表わされる化合物（以下、化合物Ｉと略称す
る）は、例えば次の方法で製造することができる。すな
わち、６−トリフルオロメチル−４Ｈ−フロ（５，２−
ｂ）インドール−２−カルボン酸エステルをＮａＯＨ、
ＫＯＨなどのアルカリで加水分解して対応するカルボン
酸とし、これを塩化チオニルなどによって対応する酸り
Ｃ１リドに変えた後、モルホリンを反応させて２−モル
ホリノカルボニル−６−トリフルオロメチル−４Ｈ−フ
ロ〔３゜２−ｂ〕インドールとする。The compound represented by General Formula 1 (hereinafter abbreviated as Compound I) can be produced, for example, by the following method. That is, 6-trifluoromethyl-4H-furo(5,2-
b) Indole-2-carboxylic acid ester with NaOH,
Hydrolyze with an alkali such as KOH to obtain the corresponding carboxylic acid, convert this into the corresponding acid C1 lid with thionyl chloride, and then react with morpholine to obtain 2-morpholinocarbonyl-6-trifluoromethyl-4H- Furo [3°2-b] shall be indole.
これに、一般式
％式％）
（式中、Ｒは前記と同意議、又はハロゲン原子を示す）
で表わされる酸ハライドを反応させて化合物Ｉを得るこ
とができる。In addition, the general formula % formula %) (in the formula, R represents the same agreement as above or a halogen atom)
Compound I can be obtained by reacting an acid halide represented by
Ｒで示されるアルキル基は直鎖または分枝鎖アルキル基
でアシ、代表的なものとして、メチル、エチル、フロヒ
ル、メチル、ペンチル、ヘキシル、ヘプチル、オクチル
、ノニル、デシル、テトラデシル、ヘキサデシル、イソ
プロピル、θθＣ−ブチル、ｔθｒｔ−メチル、イソペ
ンチル、’ｔｅｒｔ−ペンチル、１−エチルプロピル、
１−メチルヘキシル、２，４゜４−トリメチルペンチル
などの各基が挙げられる。The alkyl group represented by R is a linear or branched alkyl group, and typical examples include methyl, ethyl, fluoroyl, methyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, tetradecyl, hexadecyl, isopropyl, θθC-butyl, tθrt-methyl, isopentyl, 'tert-pentyl, 1-ethylpropyl,
Examples include groups such as 1-methylhexyl and 2,4°4-trimethylpentyl.
Ｘで示されるハロゲン原子はクロルまたはブロムである
。The halogen atom represented by X is chloro or bromine.
なお、６−トリフルオロメチル−４Ｈ−フロ〔３゜２−
ｂ：］］インドールー２−カルボン酸エステは、特開昭
５２−３０９６号に記載された方法によシ製造すること
ができる。すなわち、６−トリフルオロメチル−４Ｈ−
フロ（３，２−ｂ 〕〕インドールー２−カルボン酸エ
チルエステの製造について説明すると、４−トリフルオ
ロメチル−２−ニトロアニリンを亜硝酸ナトリウム／塩
酸でジアゾニウム塩とし、これにフランカルボン酸を塩
化第二銅存在下反応させて５−（２−ニトロ−４−トリ
フルオロメチルフェニル）−フランカルボン酸を得る。In addition, 6-trifluoromethyl-4H-furo[3゜2-
b:]] Indole-2-carboxylic acid ester can be produced by the method described in JP-A-52-3096. That is, 6-trifluoromethyl-4H-
To explain the production of furo(3,2-b)]indole-2-carboxylic acid ethyl ester, 4-trifluoromethyl-2-nitroaniline is made into a diazonium salt with sodium nitrite/hydrochloric acid, and furancarboxylic acid is added to the diazonium salt. The reaction is carried out in the presence of cupric acid to obtain 5-(2-nitro-4-trifluoromethylphenyl)-furancarboxylic acid.
５−（２−二トロー４− ） ＩＪフルオロメチルフェ
ニル）″−フランカルボン酸をエタノール／硫酸でエチ
ルエステルとした後、パラジウムカーボンを触媒とする
接触還元により５−（２−アミノ−４−トリフルオロメ
チルフェニル）−フランカルボン酸エチルエステルを得
る。これを再び亜硝酸ナトリウム／塩酸でジアゾニウム
塩とした後、アジ化ナトリウムを反応させて５−（２−
アジド−４−）！、ｌフルオロメチルフェニル）−フラ
ンカルボン酸エチルエステルヲ得、ジクロロベンゼン中
加熱閉環して６−トリフルオロメチル−４Ｈ−−ｙ ｏ
（５，２−ｂ ） インドール−２−カルボン酸エチ
ルエステルを得る。After converting 5-(2-nitro-4-)IJfluoromethylphenyl)''-furancarboxylic acid into ethyl ester with ethanol/sulfuric acid, 5-(2-amino-4-tri- Fluoromethylphenyl)-furancarboxylic acid ethyl ester is obtained. This is again made into a diazonium salt with sodium nitrite/hydrochloric acid, and then reacted with sodium azide to form 5-(2-
Azide-4-)! , lfluoromethylphenyl)-furancarboxylic acid ethyl ester was obtained, which was ring-closed by heating in dichlorobenzene to give 6-trifluoromethyl-4H--yo.
(5,2-b) Indole-2-carboxylic acid ethyl ester is obtained.
化合物■は優れた鎮痛作用および抗炎症作用を示す。以
下、実施例および試験例を挙げて本発明の詳細な説明す
る。Compound ■ exhibits excellent analgesic and anti-inflammatory effects. The present invention will be described in detail below with reference to Examples and Test Examples.
実施例 １
６−トリフルオロメチル−４Ｈ−７０（５，２−ｂ〕イ
ンドール−２−カルボン酸エチル（ｍ、ｐ。Example 1 Ethyl 6-trifluoromethyl-4H-70(5,2-b)indole-2-carboxylate (m, p.
２２４〜２２５℃）２０２を１０％水酸化ナトリウム水
溶液１００−とアセトン１００−との混液に加え、室温
で１時間攪拌した。これを濃縮してアセトンを揮散させ
た後、塩酸酸性とし、析出した６−トリフルオロメチル
−４Ｈ−フロ（ｓ、 ２−ｂ）インドール−２−カルボ
ン酸１８７を得た。224-225°C) 202 was added to a mixture of 10% aqueous sodium hydroxide solution 100- and acetone 100- and stirred at room temperature for 1 hour. This was concentrated to volatilize the acetone, and then acidified with hydrochloric acid to obtain precipitated 6-trifluoromethyl-4H-furo(s, 2-b)indole-2-carboxylic acid 187.
これを良く乾燥後、ベンゼン２０〇−中に加え、塩化チ
オニル２０ｒｎｌを滴下して１時間加熱還流した。ベン
ゼンおよび過剰の塩化チオニルを留去、蒸発乾固し、６
−トリフルオロメチル−４Ｈ−７０（３，２−ｂ ）
インドール−２−カルボン酸クロリド１７２を得だ。こ
れをアセトン１００ｆｎｌとジクロルメタン１００ ｍ
ｌとの混液に溶解し、モルホリン１０２をジクロルメタ
ンｓｏｍｐに溶解した溶液に攪拌下滴下し、滴下終了後
、室温で６０分攪拌して水を加え、析出した結晶を渥取
、水洗し、アセトン−石油エーテルよシ再結晶して２−
モルホリノカルボニル−６−トリフルオロメチル−４Ｈ
−フロ（３，２−ｂ ）インドール１６ｆを得た。After thoroughly drying this, it was added to 200ml of benzene, 20ml of thionyl chloride was added dropwise, and the mixture was heated under reflux for 1 hour. Benzene and excess thionyl chloride were distilled off and evaporated to dryness.
-trifluoromethyl-4H-70(3,2-b)
Indole-2-carboxylic acid chloride 172 was obtained. Add this to 100fnl of acetone and 100ml of dichloromethane.
Morpholine 102 was dissolved in a mixture of dichloromethane somp and added dropwise under stirring to a solution of morpholine 102 dissolved in dichloromethane somp. After the dropwise addition was completed, the mixture was stirred at room temperature for 60 minutes, water was added, and the precipitated crystals were collected, washed with water, and acetone- Recrystallize from petroleum ether and 2-
Morpholinocarbonyl-6-trifluoromethyl-4H
-furo(3,2-b)indole 16f was obtained.
ｍ、ｐ、２’２１．５〜２２２．５℃
実施例 ２
実Ｍ例１で得だ２−モルホリノカルボニル−６−トリフ
ルオロメチル−４Ｈ−フロ（３，２−１） 、１イ／ド
ール３．ａ２をジメチルホルムアミド４０ｍ１に溶解し
た溶液を、水素化ナトリウム０．２３ ｆをジメチルホ
ルムアミド５−に懸濁しだ液に攪拌下滴下し、次いで、
アセチルクロリド０８ｆを滴下した後、室温で１時間攪
拌した。反応後、反応混液を水中に注ぎ、析出した結晶
をアセトンより再結晶して４−アセチル−２−モルホリ
ノカルボニル−６−ドリフルオロメチルーフｏ （３，
２−ｂ ）インドール（検体番号１）２．６７を得た。m, p, 2'21.5-222.5°C Example 2 2-morpholinocarbonyl-6-trifluoromethyl-4H-furo(3,2-1), 1I/dol obtained in Example 1 3. A solution of a2 dissolved in 40 ml of dimethylformamide was added dropwise to a suspension of 0.23 f of sodium hydride in 5-dimethylformamide under stirring, and then
After adding acetyl chloride 08f dropwise, the mixture was stirred at room temperature for 1 hour. After the reaction, the reaction mixture was poured into water, and the precipitated crystals were recrystallized from acetone to give 4-acetyl-2-morpholinocarbonyl-6-dolifluoromethylform (3,
2-b) Indole (sample number 1) 2.67 was obtained.
ｍ、ｐ、 ’２１４〜２１５℃
実施例２と同様にして、２−モルホリノカルボニル−６
−トリフルオロメチル−４Ｈ−ノロ〔６゜２−ｂ〕イン
ドールと各種酸ハライド（Ｉｔ）を反応させ、以下の化
合物を得た。m, p, '214-215°C In the same manner as in Example 2, 2-morpholinocarbonyl-6
-Trifluoromethyl-4H-noro[6°2-b]indole and various acid halides (It) were reacted to obtain the following compounds.
検体番号 化 合 物 名
２ ２−モルホリノカルボニル−４−プ ７０ピオニル
−６−ドリフルオロメチ
ルーフロ（３，２−１） ）インドール（ｍ、ｐ＝ ２
１５〜２１７℃）
３ ４−ブチリル−２−モルホリノカル ８ボニル−６
−） ＩＪフルオロメチル−ソロ（５，２−１） 〕イ
ンドール
（ｍ、ｐ、’１７１．５〜１７２．５℃）４ ４−イン
ブチリル−２−モルホリノ ９カルボニル−６−ドリフ
ルオロメチ
ルーフロ（３，２−ｂ 〕インドール
（ｍ、’ｐ、１５６〜１５７℃）
５ ２−モルホリノカルボニル−４−バ １０レリル−
６−トリフルオロメチル−
フロ（３，２−ｂ）インドール
（ｍ、ｐ、 １４１〜１４２．５℃）
６ ４−ピバロイル−２−モルホリノ力 １１ルボニル
−６−トリフルオロメチル
−フロ［５，２−ｂ ］コインドー
ルｍ、ｐ、 １３８〜１３９℃）
４−ヘキサノイル−２−モルホリノ
カルボニル−６−ドリフルオロメチ
ルーフ（口（５，，２−１） コインドール（ｍ、ｐ、
９９〜１０２℃）
４−ヘプタノイル−２−モルホリノ
カルボニル−６−ドリフルオロメチ
ルーフロ（３，２−ｂ 〕インドール
（ｍ、ｐ、９０〜９２．５℃）
２−モルホリノカルボニル−４−オ
クタノイル−６−ドリフルオロメチ
ルーフロ（ｓ、 ２− ｂ ）インドール（ｍ、ｐ、８
９〜９０℃）
２−モルホリノカルボニル−４−ノ
ナノイル−６−ドリフルオロメチル
−フロ（、ｓ、 ２．− ｂ ：ｌインドール（ｍ、ｐ
、’＋ 、１４〜１１５℃）
２−モルホリノカルボニルｂ−４−（３゜ｓ、 ５−
トリメチルヘキサノイル）−６−ドリフルオロメチル−
フロ〔３゜
２−ｂ〕〕インドー
ルｍ、ｐ、１５７〜１５９５℃）
１２ ４−デカノイル−２−モルホリノカルボニル−６
−） ＩＪフルオロメチル−フロ（３，２−ｂ ）イン
ドール
（ｍ、ｐ、８６〜８９℃）
試験例１〔酢酸ライジング法による鎮痛作用〕体重２０
７前後の（ｌｄＹ系雄性マウス（１群１０匹）に０．７
％酢酸０．１７！／１０Ｆを腹腔内投与しライジング症
状を生じさせた。０．３％ＣＭＯ溶液に化合物１１ｏｍ
ｙ／Ｋｒを懸濁した液を酢酸投与３０分前に経口投与し
、酢酸投与１０分後から１０分間のライジングを調べ、
その抑制率をめた。Sample number Compound name 2 2-morpholinocarbonyl-4-70pionyl-6-dolifluoromethyl-furo(3,2-1)) indole (m, p=2
15-217°C) 3 4-Butyryl-2-morpholinocal 8bonyl-6
-) IJ fluoromethyl-solo (5,2-1)] indole (m, p, '171.5-172.5°C) 4 4-inbutyryl-2-morpholino 9 carbonyl-6-dolifluoromethyl-furo ( 3,2-b] indole (m, 'p, 156-157°C) 5 2-morpholinocarbonyl-4-ba 10 leryl-
6-Trifluoromethyl-furo(3,2-b)indole (m, p, 141-142.5°C) 6 4-pivaloyl-2-morpholinol 11 Rubonyl-6-trifluoromethyl-furo[5,2 -b ] Coindore m, p, 138-139°C) 4-hexanoyl-2-morpholinocarbonyl-6-dolifluoromethylfu (mouth (5,,2-1) Coindore (m, p,
99-102°C) 4-heptanoyl-2-morpholinocarbonyl-6-dolifluoromethyl-furo(3,2-b]indole (m, p, 90-92.5°C) 2-morpholinocarbonyl-4-octanoyl- 6-Dolifluoromethyl-furo(s, 2-b)indole(m,p,8
9-90°C) 2-morpholinocarbonyl-4-nonanoyl-6-dolifluoromethyl-furo(,s, 2.- b :l indole(m, p
, '+, 14-115°C) 2-morpholinocarbonyl b-4-(3°s, 5-
trimethylhexanoyl)-6-dolifluoromethyl-
Furo[3゜2-b]]indole m, p, 157-1595°C) 12 4-decanoyl-2-morpholinocarbonyl-6
-) IJ fluoromethyl-furo(3,2-b)indole (m, p, 86-89°C) Test Example 1 [Analgesic effect by acetic acid rising method] Body weight 20
Around 7 (0.7 for ldY male mice (10 mice per group)
% Acetic acid 0.17! /10F was administered intraperitoneally to induce writhing symptoms. Compound 11om in 0.3% CMO solution
A suspension of y/Kr was orally administered 30 minutes before acetic acid administration, and the rising was observed for 10 minutes from 10 minutes after acetic acid administration.
The suppression rate was improved.
試験例２〔カラゲニン浮腫法による抗炎症作用〕゛体重
１２０２前後のウィスター系雄性ラット（１群１０匹）
に化合物１１００■／Ｋｇを経口投与し、１時間後に０
．５％カラゲニンｌ １ ｄ／ラットを右後肢足踪下に
注射して、その足溶積を測定し、カラゲニン注射前の足
容積に対する浮腫率から面積法によシ抑制率を算出した
。Test Example 2 [Anti-inflammatory effect by carrageenan edema method] Male Wistar rats weighing around 1202 kg (10 rats per group)
1100 μg/Kg of the compound was orally administered to
．． 5% carrageenan l 1 d/rat was injected into the lower right hind paw, the paw volume was measured, and the inhibition rate was calculated by the area method from the edema rate relative to the paw volume before carrageenan injection.
試験例１および試験例２の結果を表２に示す。The results of Test Example 1 and Test Example 2 are shown in Table 2.
表２ 鎮痛効果および抗炎症作用
１ｔ・
試験例３〔急性毒性試験〕
体重的１００２のウィスター系雄性ラット６匹に、それ
ぞれ化合物１２００η／Ｋｇを経口投与した。その結果
、実施例により得られる化合物１のいずれを投与した場
合にも死亡例は見られなかった。Table 2 Analgesic effect and anti-inflammatory effect 1t Test Example 3 [Acute toxicity test] Six male Wistar rats weighing 1002 were each orally administered 1200 η/Kg of the compound. As a result, no deaths were observed when any of the compounds 1 obtained in the Examples were administered.
特許出願人 大正製薬株式会社 代理人 弁理士 北 川 富 造Patent applicant: Taisho Pharmaceutical Co., Ltd. Agent Patent Attorney Tomizo Kitagawa
Claims (1)
ドール化合物。(1) A Freundole compound represented by the general formula % (wherein R represents an alkyl group).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58108230A JPS601184A (en) | 1983-06-16 | 1983-06-16 | Furoindole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58108230A JPS601184A (en) | 1983-06-16 | 1983-06-16 | Furoindole compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS601184A true JPS601184A (en) | 1985-01-07 |
Family
ID=14479350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58108230A Pending JPS601184A (en) | 1983-06-16 | 1983-06-16 | Furoindole compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS601184A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2249686A (en) * | 1989-11-21 | 1992-05-13 | Furuno Electric Co | Radar equipment |
-
1983
- 1983-06-16 JP JP58108230A patent/JPS601184A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2249686A (en) * | 1989-11-21 | 1992-05-13 | Furuno Electric Co | Radar equipment |
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