JPS6245870B2 - - Google Patents
Info
- Publication number
- JPS6245870B2 JPS6245870B2 JP55019289A JP1928980A JPS6245870B2 JP S6245870 B2 JPS6245870 B2 JP S6245870B2 JP 55019289 A JP55019289 A JP 55019289A JP 1928980 A JP1928980 A JP 1928980A JP S6245870 B2 JPS6245870 B2 JP S6245870B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- group
- methoxy
- acetylergoline
- hydrogen atom
- 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
- 150000001875 compounds Chemical class 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- -1 (4'-phenylpiperazino)acetylergoline Chemical compound 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000002249 anxiolytic agent Substances 0.000 claims description 2
- 230000000949 anxiolytic effect Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 230000000701 neuroleptic effect Effects 0.000 claims 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 3
- 229940025084 amphetamine Drugs 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 230000002631 hypothermal effect Effects 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- UNEIHNMKASENIG-UHFFFAOYSA-N para-chlorophenylpiperazine Chemical compound C1=CC(Cl)=CC=C1N1CCNCC1 UNEIHNMKASENIG-UHFFFAOYSA-N 0.000 description 1
- MRDGZSKYFPGAKP-UHFFFAOYSA-N para-methoxyphenylpiperazine Chemical compound C1=CC(OC)=CC=C1N1CCNCC1 MRDGZSKYFPGAKP-UHFFFAOYSA-N 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000010825 rotarod performance test Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
-
- 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
- A61P25/20—Hypnotics; Sedatives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Anesthesiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は８β−アセチルエルゴリン誘導体、そ
の製造方法及び前記化合物を含有する製剤組成物
に関する。
本発明は、一般式：
〔式中Ｒは水素原子又はメチル基を表わし、
R1は水素原子又はメトキシ基を表わし、R2は未
置換フエニル基又はハロゲン及び低級アルコキシ
基から選ばれた置換分を有する置換フエニル基を
表わす〕で示される８β−アセチルエルゴリン誘
導体及びその製剤的認容性酸付加塩を提供する。
更に本発明は、上記定義のような一般式の８
β−アセチルエルゴリン誘導体の製造方法を提供
する。この方法は、８β−ブロムアセチル−６−
メチル−エルゴン、８β−ブロムアセチル−１，
６−ジメチル−エルゴリン、８β−ブロムアセチ
ル−６−メチル−10−メトキシ−エルゴリン又は
８β−ブロムアセチル−１，６−ジメチル−10−
メトキシ−エルゴリン（本出願に相当するベルギ
ー特許861480号明細書に記載）を一般式：
〔式中R2は上記のものを表わす〕で示される
求核剤と反応させることより成る。反応は、トリ
メチルアミン又は炭酸カリウムのような塩基の存
在又は塩基の不在で実施されうる。反応は、極性
又は非極性溶剤、例えばメタノール、エタノー
ル、アセトン、ジメチルホルムアミド又はクロロ
ホルム中で周囲温度から60℃の温度で１〜４時間
の間実施される。
生成物は、公知方法、例えばクロマトグラフイ
ー及び／又は結晶化によつて、遊離塩又は製剤的
認容性酸の塩として単離され、精製される。
本発明による化合物及びその製剤的認容性酸付
加塩は、有用な不安解消剤及び神経弛緩剤であ
る。
中枢鎮静薬理作用のプロフイールは、アーウイ
ン（lrwin）によるマウス行動の観察的評価（７
日の観察後に決定的急性毒性も指示する）〔アー
ウインS.：サイコフアーマコロジア
（Psychopharma cologia），Berl.，13，222，
1968〕及びアンフエタミン誘発中枢低体温に対す
る拮抗作用によつて得られる。本発明の化合物を
用いて得られた結果は表１に記載される。
アンフエタミン誘発中枢低体温に対する拮抗作
用に関しては〔ヤンセン（Janssen）P.A.J.，ニ
ーメゲールス（Niemegeers）C.J.E.，シエレケ
ンス（Schellekens）K.H.L.及びレーナエルツ
（Lenaerts）F.M.，Arzneimittel−Forsch.17，
（７），841，1967〕、該化合物が、ｄ−アンフエタ
ミン硫酸塩10mg／Kgの腹腔内注射の30分前に１〜
10mg／Kgの用量範囲で雄マウスに経口投与され
た。アンフエタミン投与の60分後に低体温の拮抗
作用が評価された。
また本発明による化合物は、筋肉弛緩（マウス
でのアーウイン試験）及び運動失調（ラツトでの
ロータロード（Rotarod）試験）の誘発の場合25
mg／Kgの経口用量まで不活性であることも判つ
た。
The present invention relates to 8β-acetylergoline derivatives, processes for their production, and pharmaceutical compositions containing said compounds. The present invention is based on the general formula: [In the formula, R represents a hydrogen atom or a methyl group,
R 1 represents a hydrogen atom or a methoxy group, and R 2 represents an unsubstituted phenyl group or a substituted phenyl group having a substituent selected from a halogen and a lower alkoxy group] and preparations thereof provides acid addition salts that are accommodating. Furthermore, the present invention provides 8 of the general formula as defined above.
A method for producing a β-acetylergoline derivative is provided. This method uses 8β-bromoacetyl-6-
Methyl-ergon, 8β-bromoacetyl-1,
6-dimethyl-ergoline, 8β-bromoacetyl-6-methyl-10-methoxy-ergoline or 8β-bromoacetyl-1,6-dimethyl-10-
Methoxy-ergoline (described in Belgian Patent No. 861480 corresponding to this application) has the general formula: It consists of reacting with a nucleophile represented by the formula [wherein R 2 represents the above]. The reaction may be carried out in the presence or absence of a base such as trimethylamine or potassium carbonate. The reaction is carried out in a polar or non-polar solvent such as methanol, ethanol, acetone, dimethylformamide or chloroform at a temperature from ambient to 60° C. for a period of 1 to 4 hours. The products are isolated and purified as free salts or salts of pharmaceutically acceptable acids by known methods, such as chromatography and/or crystallization. The compounds according to the invention and their pharmaceutically acceptable acid addition salts are useful anxiolytics and neuroleptics. The profile of central sedative pharmacology was determined by observational evaluation of mouse behavior by lrwin (7).
Definitive acute toxicity is also indicated after a day of observation) [Irwin S.: Psychopharmacologia, Berl., 13, 222,
1968] and antagonism of amphetamine-induced central hypothermia. The results obtained using the compounds of the invention are listed in Table 1. Regarding the antagonism of amphetamine-induced central hypothermia [Janssen PAJ, Niemegeers CJE, Schellekens KHL and Lenaerts FM, Arzneimittel-Forsch.
(7), 841, 1967], the compound was administered from 1 to
It was administered orally to male mice at a dose range of 10 mg/Kg. Antagonism of hypothermia was assessed 60 minutes after amphetamine administration. The compounds according to the invention are also effective for inducing muscle relaxation (Irwin test in mice) and ataxia (Rotarod test in rats).
It was also found to be inactive up to oral doses of mg/Kg.
【表】
化合物の上記参照番号は以下の例で説明する。
次に実施例により本発明を説明する。
例 １
６−メチル−８β−（4′−フエニルピペラジ
ノ）−アセチルエルゴリン（355／1083）
８β−ブロムアセチル−６−メチル−エルゴリ
ン2.5ｇとＮ−フエニルピペラジン2.34ｇとのエ
タノール30ml中の溶液を室温で４時間放置した。
その溶液から真空で溶剤を蒸発させ、残留物をク
ロロホルムにとり、水洗した。このものから溶剤
を真空で蒸発させた後、残留物に、溶離剤として
クロロホルム：メタノール（容積で99：１）の混
合物を用いてシリカゲルのコラムによりクロマト
グラフイーを施す。同じ生成物を含有することを
示すフラクシヨンを集め、メタンスルホン酸
2molで処理する。生ずる塩をエタノールから結
晶化して６−メチル−８β−（4′−フエニル−ピ
ペラジノ）アセチルエルゴリンのビス−メタンス
ルホネート（mp219〜221℃）３ｇを得た。
例 ２
６−メチル−８β−〔4′−（ｐ−クロルフエニ
ル）−ピペラジノ〕−アセチルエルゴリン
（355／1084）
Ｎ−（ｐ−クロルフエニル）−ピペラジンを使用
するほかは例１と同様に操作して、表題の化合物
のビス−メタンスルホネート（mp.242〜244℃）
を60％の収率で得た。
例 ３
６−メチル−８β−〔4′−（ｐ−メトキシフエニ
ル）−ピペラジノ〕−アセチルエルゴリン
（355／1087）
Ｎ−（ｐ−メトキシフエニル）−ピペラジンを使
用するほかは例１と同様に操作して表題の化合物
のビス−メタンスルホネート（mp.216〜218℃）
を65％の収率で得た。
例 ４
１，６−ジメチル−８β−〔4′−（ｐ−クロルフ
エニル）−ピペラジノ〕−アセチルエルゴリン
８β−ブロムアセチル−１，６−ジメチル−エ
ルゴリンを使用するほかは例２と同様に操作し
て、表題の化合物のビス−メタンスルホネート
（mp.256〜258℃）が60％の収率で得られた。
例 ５
６−メチル−10−メトキシ−８β−（4′−フエ
ニルピペラジノ）−アセチルエルゴリン
８β−ブロムアセチル−６−メチル−10−メト
キシ−エルゴリンを使用するほかは例１と同様に
操作して表題の化合物のビス−メタンスルホネー
トを70％の収率で得た。
例 ６
１，６−ジメチル−10−メトキシ−８β−
（4′−フエニルピペラジノ）−アセチルエルゴリ
ン
８β−ブロムアセチル−１，６−ジメチル−10
−メトキシ−エルゴリンを使用するほかは例１と
同様に操作して表題の化合物のビス−メタンスル
ホネートを67％の収率で得た。TABLE The above reference numbers for compounds are illustrated in the examples below. Next, the present invention will be explained with reference to examples. Example 1 6-Methyl-8β-(4′-phenylpiperazino)-acetylergoline (355/1083) Ethanol of 2.5 g of 8β-bromoacetyl-6-methyl-ergoline and 2.34 g of N-phenylpiperazine The solution in 30ml was left at room temperature for 4 hours.
The solution was evaporated in vacuo and the residue was taken up in chloroform and washed with water. After evaporation of the solvent from this in vacuo, the residue is chromatographed on a column of silica gel using a mixture of chloroform:methanol (99:1 by volume) as eluent. Collect the fractions shown to contain the same product and collect the methanesulfonic acid
Treat with 2mol. The resulting salt was crystallized from ethanol to yield 3 g of 6-methyl-8β-(4'-phenyl-piperazino)acetylergoline bis-methanesulfonate (mp 219-221°C). Example 2 6-Methyl-8β-[4'-(p-chlorophenyl)-piperazino]-acetylergoline (355/1084) Proceed as in Example 1 except that N-(p-chlorophenyl)-piperazine is used. bis-methanesulfonate of the title compound (mp. 242-244°C)
was obtained in 60% yield. Example 3 6-Methyl-8β-[4'-(p-methoxyphenyl)-piperazino]-acetylergoline (355/1087) Same as Example 1 except using N-(p-methoxyphenyl)-piperazine. Bis-methane sulfonate (mp.216-218℃) of the title compound was prepared in the same manner.
was obtained in 65% yield. Example 4 1,6-Dimethyl-8β-[4'-(p-chlorophenyl)-piperazino]-acetylergoline Proceed as in Example 2, except using 8β-bromoacetyl-1,6-dimethyl-ergoline. The bis-methane sulfonate (mp. 256-258°C) of the title compound was obtained in 60% yield. Example 5 6-Methyl-10-methoxy-8β-(4'-phenylpiperazino)-acetylergoline Same as Example 1 except using 8β-bromoacetyl-6-methyl-10-methoxy-ergoline. Operation gave the bis-methane sulfonate of the title compound in 70% yield. Example 6 1,6-dimethyl-10-methoxy-8β-
(4'-phenylpiperazino)-acetylergoline 8β-bromoacetyl-1,6-dimethyl-10
The bis-methanesulfonate of the title compound was obtained in a yield of 67% by the same procedure as in Example 1, except that -methoxy-ergoline was used.
Claims (1)
R1は水素原子又はメトキシ基を表わし、R2は未
置換フエニル基又はハロゲン及び低級アルコキシ
基から選ばれた置換分を有する置換フエニル基を
表わす〕で示される８β−アセチルエルゴリン誘
導体又はその製剤的認容性酸付加塩。 ２ ６−メチル−８β−（4′−フエニルピペラジ
ノ）−アセチルエルゴリンである特許請求の範囲
第１項記載の化合物。 ３ ６−メチル−８β−〔4′−（ｐ−クロルフエニ
ル）−ピペラジノ〕−アセチルエルゴリンである特
許請求の範囲第１項記載の化合物。 ４ ６−メチル−８β−〔4′−（ｐ−メトシキフエ
ニル）−ピペラジノ〕−アセチルエルゴリンである
特許請求の範囲第１項記載の化合物。 ５ １，６−ジメチル−８β−〔4′−（ｐ−クロル
フエニル）−ピペラジノ〕−アセチルエルゴリンで
ある特許請求の範囲第１項記載の化合物。 ６ ６−メチル−10−メトキシ−８β−（4′−フ
エニルピペラジノ）−アセチルエルゴリンである
特許請求の範囲第１項記載の化合物。 ７ １，６−ジメチル−10−メトキシ−８β−
（4′−フエニルピペラジノ）アセチルエルゴリン
である特許請求の範囲第１項記載の化合物。 ８ 一般式： 〔式中Ｒは水素原子又はメチル基を表わし、
R1は水素原子又はメトキシ基を表わし、R2は未
置換フエニル基又はハロゲン及び低級アルコキシ
基から選ばれた置換分を有する置換フエニル基を
表わす〕で示される８β−アセチルエルゴリン誘
導体を製造するに当たり、８β−ブロムアセチル
−６−メチル−エルゴリン、８β−ブロムアセチ
ル−１，６−ジメチル−エルゴリン、８β−ブロ
ムアセチル−６−メチル−10−メトキシ−エルゴ
リン又は８β−ブロムアセチル−１，６−ジメチ
ル−10−メトキシ−エルゴリンを溶剤中で周囲温
度から60℃までの温度で１〜６時間の間一般式
： 〔式中R2は前記のものを表わす〕で示される
求核剤と反応させることを特徴とする前記８β−
アセチルエルゴリン誘導体の製造方法。 ９ 反応を塩基の存在で実施する特許請求の範囲
第８項記載の方法。 １０ 塩基がトリメチルアミン又は炭酸カリウム
である特許請求の範囲第９項記載の方法。 １１ 溶剤がメタノール、エタノール、アセト
ン、ジメチルホルムアミド又はクロロホルムであ
る特許請求の範囲第８項から第１０項までのいづ
れか１項記載の方法。 １２ 一般式： 〔式中Ｒは水素原子又はメチル基を表わし、
R1は水素原子又はメトキシ基を表わし、R2は未
置換フエニル基又はハロゲン及び低級アルコキシ
基から選ばれた置換分を有する置換フエニル基を
表わす〕で示される８β−アセチルエルゴリン誘
導体又はその製剤的認容性酸付加塩を含有する不
安解消及び神経弛緩作用を有する製剤組成物。[Claims] 1. General formula: [In the formula, R represents a hydrogen atom or a methyl group,
R 1 represents a hydrogen atom or a methoxy group, R 2 represents an unsubstituted phenyl group or a substituted phenyl group having a substituent selected from halogen and lower alkoxy group] or a preparation thereof Acceptable acid addition salts. 2. The compound according to claim 1, which is 6-methyl-8β-(4'-phenylpiperazino)-acetylergoline. 3. The compound according to claim 1, which is 6-methyl-8β-[4'-(p-chlorophenyl)-piperazino]-acetylergoline. 4. The compound according to claim 1, which is 6-methyl-8β-[4'-(p-methoxyphenyl)-piperazino]-acetylergoline. 5. The compound according to claim 1, which is 1,6-dimethyl-8β-[4'-(p-chlorophenyl)-piperazino]-acetylergoline. 6. The compound according to claim 1, which is 6-methyl-10-methoxy-8β-(4'-phenylpiperazino)-acetylergoline. 7 1,6-dimethyl-10-methoxy-8β-
The compound according to claim 1, which is (4'-phenylpiperazino)acetylergoline. 8 General formula: [In the formula, R represents a hydrogen atom or a methyl group,
R 1 represents a hydrogen atom or a methoxy group, R 2 represents an unsubstituted phenyl group or a substituted phenyl group having a substituent selected from halogen and lower alkoxy group] 8β-bromoacetyl-6-methyl-ergoline, 8β-bromoacetyl-1,6-dimethyl-ergoline, 8β-bromoacetyl-6-methyl-10-methoxy-ergoline or 8β-bromoacetyl-1,6- Dimethyl-10-methoxy-ergoline in a solvent at temperatures from ambient to 60°C for 1 to 6 hours with the general formula: The 8β-
A method for producing an acetyl ergoline derivative. 9. The method according to claim 8, wherein the reaction is carried out in the presence of a base. 10. The method according to claim 9, wherein the base is trimethylamine or potassium carbonate. 11. The method according to any one of claims 8 to 10, wherein the solvent is methanol, ethanol, acetone, dimethylformamide or chloroform. 12 General formula: [In the formula, R represents a hydrogen atom or a methyl group,
R 1 represents a hydrogen atom or a methoxy group, R 2 represents an unsubstituted phenyl group or a substituted phenyl group having a substituent selected from halogen and lower alkoxy group] or a preparation thereof A pharmaceutical composition having anxiolytic and neuroleptic effects, which contains an acid addition salt that is acceptable to humans.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7906023 | 1979-02-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55113779A JPS55113779A (en) | 1980-09-02 |
| JPS6245870B2 true JPS6245870B2 (en) | 1987-09-29 |
Family
ID=10503318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1928980A Granted JPS55113779A (en) | 1979-02-20 | 1980-02-20 | 8 betaaacetylergoline derivative*its manufacture*medicine composition containing it and having antidepressive and neuroleptic activity |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS55113779A (en) |
| BE (1) | BE879822A (en) |
| DE (1) | DE3000901A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2550477B2 (en) * | 1994-05-27 | 1996-11-06 | 株式会社オーケープリント | Memory device component mounting plate and memory unit |
| WO2019215791A1 (en) | 2018-05-07 | 2019-11-14 | 株式会社ニューロシューティカルズ | Medical tube position confirmation system |
| WO2020059087A1 (en) | 2018-09-20 | 2020-03-26 | 株式会社ニューロシューティカルズ | Medical tube position confirmation system |
| WO2021084700A1 (en) | 2019-10-31 | 2021-05-06 | 株式会社ニューロシューティカルズ | Medical tube position confirmation system |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8501078D0 (en) * | 1985-01-16 | 1985-02-20 | Erba Farmitalia | Piperazin-1-yl-ergo-line derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6818658A (en) * | 1968-01-18 | 1969-07-22 | ||
| GB1580448A (en) * | 1976-12-06 | 1980-12-03 | Farmaceutici Italia | 8 -acetyl-6-methyl-ergoline i derivatives |
-
1979
- 1979-11-05 BE BE0/197964A patent/BE879822A/en not_active IP Right Cessation
-
1980
- 1980-01-11 DE DE19803000901 patent/DE3000901A1/en not_active Withdrawn
- 1980-02-20 JP JP1928980A patent/JPS55113779A/en active Granted
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2550477B2 (en) * | 1994-05-27 | 1996-11-06 | 株式会社オーケープリント | Memory device component mounting plate and memory unit |
| WO2019215791A1 (en) | 2018-05-07 | 2019-11-14 | 株式会社ニューロシューティカルズ | Medical tube position confirmation system |
| WO2020059087A1 (en) | 2018-09-20 | 2020-03-26 | 株式会社ニューロシューティカルズ | Medical tube position confirmation system |
| WO2021084700A1 (en) | 2019-10-31 | 2021-05-06 | 株式会社ニューロシューティカルズ | Medical tube position confirmation system |
| EP4052692A1 (en) | 2019-10-31 | 2022-09-07 | Otsuka Pharmaceutical Factory, Inc. | Medical tube position confirmation system |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55113779A (en) | 1980-09-02 |
| DE3000901A1 (en) | 1980-08-28 |
| BE879822A (en) | 1980-03-03 |
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