JPH0443065B2 - - Google Patents
Info
- Publication number
- JPH0443065B2 JPH0443065B2 JP58086527A JP8652783A JPH0443065B2 JP H0443065 B2 JPH0443065 B2 JP H0443065B2 JP 58086527 A JP58086527 A JP 58086527A JP 8652783 A JP8652783 A JP 8652783A JP H0443065 B2 JPH0443065 B2 JP H0443065B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- blood pressure
- cyano
- compounds
- 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 - Lifetime
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Description
この発明は、２（1H）ピリジノン誘導体、その
製造法およびそれを含む医薬に関するものであ
る。
特に、この発明は、式（）
〔式中、
R1はシアノによりモノ置換もしくはジ置換さ
れたフエニル、
R2は水素または炭素原子数１ないし４のアル
キルである〕
で示される化合物の遊離形または塩
で示される化合物（以下、「この発明の化合物」
という）を提供するものである。
便宜上、この発明の化合物を式（）の互変異
性形で示すことにする。しかし、この発明は、例
えばイミノ形のようなあらゆる互変異性形を含む
ものである。
フエニル環はモノ置換されているのが好まし
い。モノ置換されている場合、置換基はパラ位に
存在するのが好ましい。ジ置換されている場合、
置換基はメタ位とパラ位に存在するのが好まし
い。
R2として好ましいのは炭素原子数１−４のア
ルキルである。
アルキルとして好ましいのは、炭素原子数１ま
たは２、特に１のものである。
この発明の化合物は、式（）
（式中、R1およびR2は上記の意味、Rxは脱離
基を示す）
で示される化合物を、式（）
で示される化合物と反応させることからなる方法
によつて製造することができる。
上記の方法は、同様な３−シアノまたは３−カ
ルバモイル−２（1H）−ピリジノン誘導体製造の
ための慣用方法によつて行なうことができる。
Rxは、ジ（低級）アルキルアミノ、特にジメチ
ルアミノまたはジエチルアミノのような、アセト
アミド化合物との閉環反応に慣用される基であつ
てよい。反応は、エタノールのような不活性溶媒
中で行なうのが好ましい。反応温度は、室温ない
し反応混合物の沸点附近が適当である。また、強
アルカリ性条件を用いるのが好ましい。
しかし、酸性媒体中、例えば酢酸の存在下でも
この反応を行なうことができる。
この発明の化合物は、公知の方法と同様にして
反応系から単離し精製することができる。
この発明の化合物は、遊離の形でも塩の形でも
存在し得る。遊離形は慣用方法により塩に変換す
ることができ、その逆も可能である。酸付加塩を
形成するために好適な酸には、塩酸、マロン酸、
ｐ−トルエンスルホン酸およびメタンスルホン酸
が含まれる。アニオン性塩を形成するために好適
な塩基には、水酸化ナトリウムおよびカリウムが
含まれる。アニオン塩の形の化合物は、通常イミ
ノール形が優勢である。
出発原料は公知の方法により得ることができ
る。式（）においてRxがジ（低級）アルキル
アミノ化合物は、例えば式（）
（式中、R1およびR2は上記の意味）
で示される対応化合物を、Ｎ，Ｎ−ジ（低級）ア
ルキルホルムアミド・ジ（低級）アルキルアセタ
ール、好ましくはＮ，Ｎ−ジメチルホルムアミ
ド・ジメチルまたはジエチルアセタールと反応さ
せることにより得ることができる。
式（）の化合物は、公知の方法にしたがつて
得ることができる。
個々の出発原料の製造法を特に記載しないもの
は、公知方法または上記と同様の方法によつて製
造することができる。
以下の実施例において、温度はすべて摂氏の度
を示し、未補正である。
実施例 １
５−（４−シアノフエニル）−１，２−ジヒドロ
−６−メチル−２−オキソピリジン−３−カル
ボニトリルの製造（上記方法の変法）。
シアン酢酸アミド6.2ｇをナトリウム1.14ｇと
無水エタノール200mlの新製した溶液に加える。
４−ジメチルアミノ−３−（４−シアノフエニル）
−３−ブテン−２−オン10.6ｇを加え、溶液を沸
点で５時間撹拌すると、標記化合物のナトリウム
塩がすぐに析出し始める。混合物を放冷し、結晶
性生成物を取し、エタノールおよびエーテルで
洗浄する。（ナトリウム塩；mp＞300℃）（遊離
体：mp＞300℃）。
出発原料の４−ジメチルアミノ−３−（４−シ
アノフエニル）−３−ブテン−２−オン〔bp
（0.005mmHg）＝155−160℃〕は、１−（４−シア
ノフエニル）−２−プロパノンを４，４−ジメチ
ルホルムアミド・ジメチルアセタールと80℃で１
時間加熱して得られる。
この発明の化合物は、薬理的効果を有する。
この発明の化合物は、標準的試験結果の示すと
ころによると、強心作用を有する。例えば、正常
緊張状態のニユマール（Numal）麻酔した犬に
対して約0.02mg／Kgないし約２mg／Kgを静脈内投
与すると、左心室の収縮力増加が認められる。
試験方法は次の通りである。
体重10ないし15Kgの各性の犬を用いる。麻酔剤
として、ニユマールを65mg／Kgの用量で静脈注射
する。動物を手術台上に仰臥位で固定する。通常
操作後、ヘパリン化したカテーテルをラジオロジ
−制御下に右頚動脈に沿い左心室に挿入し、圧力
の伝達をドーナー・メンブラン（グールド・スタ
ータムP23Gb）により記録する。血圧上昇を時間
の関数としてHSE−フイジオデイフアレンシエ
ーターで計算し記録する。左心室の血圧上昇は、
心臓の収縮力の指標となる。血圧差の大きさはmm
Hg／秒で示す。適当な体温（約36ないし37℃）
を一定に保つ。約40分間の対照期間後、試験物質
を大腿静脈に注射し、その記録または計算パラメ
ーターを観察する。
強心活性は、後負荷減退作用を伴なつている。
したがつて、上記麻酔犬試験において、約0.2
mg／Kgないし約２mg／Kgの静脈注射後に動脈血圧
と全末梢抵抗の減少が認められる。
動脈血圧の測定のために、ヘパリン化したカテ
ーテルをラジオロジー制御下に左頚動脈を経て大
動脈基部に挿入する。動脈血圧は、スタータム・
プレツシヤー・トランスデユーサーP23ACを用
い、収縮期および拡張期血圧を精密に求めて測定
する。平均動脈血圧は、拡張期血圧に幅
〔P(収縮期)−P(拡張期)〕の1/3を加えることによ
り計算する。
全末梢抵抗（PR）は、下式にしたがつて、ダ
イン・秒・cm-5の単位で求めた。
PR＝平均動脈血圧−左心室拡張期血圧／心拍出量×80
（心拍出量の測定は、ラジオロジー制御下に右
頚静脈に挿入したカテーテルを用い、熱希釈法に
したがつて行なう。）
さらに、この発明の化合物は、実施例１の化合
物が示すように、予期されない長期持続作用を有
し、予期されない程良好な耐容性を示す。例え
ば、頻脈は驚くほど僅かしか伴なわない。
この発明の化合物の毒性は、例えば実施例１の
化合物におけるLD50＞100mg／Kg（マウス）で示
されるように、低レベルである。
したがつて、この発明の化合物は特に強心薬と
して、例えば心不全の治療に有用である。
好ましい化合物は、実施例１の化合物である。
１日の指示用量は約10mgないし約500mgであり、
例えば経口投与により１日２ないし４回適当に分
割投与するか、または持効性製剤として投与す
る。１日用量の例は10mgないし100mgである。
この発明の化合物は、例えばジゴキシンに対す
る公知の基準と同様に投与することができる。
個々の化合物に対する適当な１日用量は、その相
対活性のような多数の要因によつて変る。例え
ば、実施例１の化合物の上記ニユマール麻酔犬に
おける試験結果をジゴキシンのそれと比較する
と、下記のような特性を有する。
The present invention relates to a 2(1H) pyridinone derivative, a method for producing the same, and a medicament containing the same. In particular, this invention uses the formula () [In the formula, R 1 is phenyl mono- or di-substituted with cyano, and R 2 is hydrogen or alkyl having 1 to 4 carbon atoms.] "Compound of this invention"
). For convenience, the compounds of this invention will be shown in their tautomeric form of formula (). However, the invention includes all tautomeric forms, such as the imino form. Preferably, the phenyl ring is monosubstituted. When monosubstituted, the substituent is preferably in the para position. If di-substituted,
Preferably, the substituents are present in the meta and para positions. Preferred as R 2 is alkyl having 1 to 4 carbon atoms. Preferred alkyls are those having 1 or 2, especially 1, carbon atom. The compound of this invention has the formula () (In the formula, R 1 and R 2 have the above meanings, and R x represents a leaving group.) A compound represented by the formula () It can be produced by a method consisting of reacting with a compound represented by: The above method can be carried out by similar conventional methods for preparing 3-cyano or 3-carbamoyl-2(1H)-pyridinone derivatives.
R x may be a group customary for ring-closing reactions with acetamide compounds, such as di(lower)alkylamino, especially dimethylamino or diethylamino. Preferably, the reaction is carried out in an inert solvent such as ethanol. The reaction temperature is suitably between room temperature and around the boiling point of the reaction mixture. Further, it is preferable to use strongly alkaline conditions. However, the reaction can also be carried out in an acidic medium, for example in the presence of acetic acid. The compound of this invention can be isolated from the reaction system and purified in the same manner as known methods. The compounds of this invention can exist in free or salt form. The free form can be converted into the salt and vice versa by conventional methods. Suitable acids for forming acid addition salts include hydrochloric acid, malonic acid,
Includes p-toluenesulfonic acid and methanesulfonic acid. Suitable bases for forming anionic salts include sodium and potassium hydroxide. In the anionic salt form of the compound, the iminol form is usually predominant. Starting materials can be obtained by known methods. In the formula (), R x is a di(lower) alkylamino compound, for example, the formula () (In the formula, R 1 and R 2 have the above-mentioned meanings.) It can be obtained by reacting with diethyl acetal. The compound of formula () can be obtained according to known methods. If the manufacturing method of each starting material is not specifically described, it can be manufactured by a known method or a method similar to the above. In the examples below, all temperatures are given in degrees Celsius and are uncorrected. Example 1 Preparation of 5-(4-cyanophenyl)-1,2-dihydro-6-methyl-2-oxopyridine-3-carbonitrile (modification of the above process). Add 6.2 g of cyanacetamide to a fresh solution of 1.14 g of sodium and 200 ml of absolute ethanol.
4-dimethylamino-3-(4-cyanophenyl)
10.6 g of -3-buten-2-one are added and the solution is stirred at boiling point for 5 hours, whereupon the sodium salt of the title compound begins to precipitate out. The mixture is allowed to cool and the crystalline product is collected and washed with ethanol and ether. (sodium salt; mp>300°C) (educt: mp>300°C). Starting material 4-dimethylamino-3-(4-cyanophenyl)-3-buten-2-one [bp
(0.005mmHg) = 155-160℃] is 1-(4-cyanophenyl)-2-propanone with 4,4-dimethylformamide dimethyl acetal at 80℃.
Obtained by heating for hours. The compounds of this invention have pharmacological effects. The compounds of this invention have cardiotonic effects as shown by standard test results. For example, when about 0.02 mg/Kg to about 2 mg/Kg is intravenously administered to a dog under Numal anesthesia in a normotonic state, an increase in the contractile force of the left ventricle is observed. The test method is as follows. Dogs of each sex weighing 10 to 15 kg are used. As an anesthetic, Nyumar is injected intravenously at a dose of 65 mg/Kg. Fix the animal in supine position on the operating table. After normal operation, a heparinized catheter is inserted under radiological control along the right carotid artery into the left ventricle, and pressure transmission is recorded through a Donner membrane (Gould Sturtum P23Gb). The increase in blood pressure as a function of time is calculated and recorded with an HSE-physiodifferentiator. Increased left ventricular blood pressure is
It is an indicator of the contractile force of the heart. The size of the blood pressure difference is mm
Expressed in Hg/sec. Appropriate body temperature (approximately 36 to 37℃)
keep constant. After a control period of approximately 40 minutes, the test substance is injected into the femoral vein and the recorded or calculated parameters are observed. Cardiac activity is accompanied by an afterload reducing effect.
Therefore, in the above anesthesia dog test, approximately 0.2
A decrease in arterial blood pressure and total peripheral resistance is observed after intravenous injection of mg/Kg to about 2 mg/Kg. For measurement of arterial blood pressure, a heparinized catheter is inserted under radiological control into the aortic root via the left carotid artery. Arterial blood pressure is statum
Accurately determine and measure systolic and diastolic blood pressure using a pressure transducer P23AC. Mean arterial blood pressure is calculated by adding 1/3 of the width [P ( systolic ) - P ( diastolic ) ] to the diastolic blood pressure. Total peripheral resistance (PR) was determined in units of dyne seconds cm -5 according to the formula below. PR = mean arterial blood pressure - left ventricular diastolic blood pressure / cardiac output x 80 (cardiac output was measured using a catheter inserted into the right jugular vein under radiology control and according to the thermodilution method. Furthermore, the compounds of this invention have an unexpectedly long-lasting action and are unexpectedly well tolerated, as shown by the compound of Example 1. For example, tachycardia is surprisingly rare. The toxicity of the compounds of this invention is at a low level, as shown for example by the LD 50 >100 mg/Kg (mouse) for the compound of Example 1. The compounds of this invention are therefore particularly useful as cardiotonic agents, for example in the treatment of heart failure. A preferred compound is the compound of Example 1. The recommended daily dose is about 10 mg to about 500 mg;
For example, the drug may be administered orally in divided doses 2 to 4 times a day, or as a sustained-release preparation. Examples of daily doses are 10 mg to 100 mg. The compounds of this invention can be administered analogously to known standards for digoxin, for example.
The appropriate daily dose for a particular compound will vary depending on a number of factors, such as its relative activity. For example, when the test results of the compound of Example 1 in the above-mentioned anonymous anesthetized dog are compared with those of digoxin, it has the following properties.
【表】
したがつて、この化合物は、ジゴキシンに対す
る公知の用量と同等またはそれより低い用量で投
与し得ることがわかる。
この発明の化合物は、遊離の形でも医薬上許容
される塩の形でも投与することができる。このよ
うな塩は遊離体と同じオーダーの活性を示し、慣
用方法により容易に製造される。この発明はま
た、この発明の化合物の遊離体または医薬上許容
される塩と、医薬用担体または希釈剤からなる医
薬組成物を提供する。このような組成物は、例え
ば溶液または錠剤の形にすることができる。溶液
製造のために、シクロデキストリン、例えばβ−
シクロデキストリンのような溶解剤または安定剤
を適宜加えることができる。It can therefore be seen that this compound can be administered at doses comparable to or lower than known doses for digoxin. The compounds of this invention can be administered in free form or in the form of pharmaceutically acceptable salts. Such salts exhibit activity on the same order of magnitude as the educt and are readily prepared by conventional methods. This invention also provides a pharmaceutical composition comprising a free form or a pharmaceutically acceptable salt of a compound of this invention and a pharmaceutical carrier or diluent. Such compositions can be in the form of solutions or tablets, for example. For solution preparation, cyclodextrins, e.g. β-
Solubilizers or stabilizers such as cyclodextrins can be added as appropriate.
Claims (1)
れたフエニル、 R2は水素または炭素原子数１ないし４のアル
キルである〕 で示される化合物の遊離形または塩。 ２ ５−（４−シアノフエニル）−１，２−ジヒド
ロ−６−メチル−２−オキソピリジン−３−カル
ボニトリルの遊離形または塩である、特許請求の
範囲第１項記載の化合物。 ３ 式（） 〔式中、 R1はシアノによりモノ置換もしくはジ置換さ
れたフエニル、 R2は水素または炭素原子数１ないし４のアル
キルである〕 で示される化合物の遊離形 または医薬上許容される塩を有効成分として含
む、強心剤。 ４ 式（） （式中、R1およびR2は後記の意味、Rxは脱離
基を示す） で示される化合物を、式（） で示される化合物と反応させることからなる、 式（） 〔式中、 R1はシアノによりモノ置換もしくはジ置換さ
れたフエニル、 R2は水素または炭素原子数１ないし４のアル
キルである〕 で示される化合物の製造法。[Claims] 1 Formula () A free form or salt of a compound represented by the following formula: wherein R 1 is phenyl mono- or di-substituted with cyano, and R 2 is hydrogen or C 1 -C 4 alkyl. 2. The compound according to claim 1, which is the free form or salt of 5-(4-cyanophenyl)-1,2-dihydro-6-methyl-2-oxopyridine-3-carbonitrile. 3 formula () [In the formula, R 1 is phenyl mono- or di-substituted with cyano, and R 2 is hydrogen or alkyl having 1 to 4 carbon atoms.] Contains a cardiotonic agent as an ingredient. 4 formula () (In the formula, R 1 and R 2 have the meanings given below, and R x represents a leaving group.) A compound represented by the formula () consisting of reacting with a compound represented by the formula () [In the formula, R 1 is phenyl mono- or di-substituted with cyano, and R 2 is hydrogen or alkyl having 1 to 4 carbon atoms].
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH308782 | 1982-05-18 | ||
| CH3087/82-6 | 1982-05-18 | ||
| CH3091/82-8 | 1982-05-18 | ||
| CH837/83-4 | 1983-02-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58213759A JPS58213759A (en) | 1983-12-12 |
| JPH0443065B2 true JPH0443065B2 (en) | 1992-07-15 |
Family
ID=4248332
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58086527A Granted JPS58213759A (en) | 1982-05-18 | 1983-05-17 | 2(1h)-pyridinone derivative, manufacture and medicine |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS58213759A (en) |
| BE (1) | BE896678A (en) |
| ZA (1) | ZA833584B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0200024B1 (en) | 1985-04-30 | 1992-07-01 | ARZNEIMITTELWERK DRESDEN GmbH | 3-cyano-pyridines, process for their preparation and their pharmaceutical use |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1507957A (en) * | 1975-03-25 | 1978-04-19 | Byk Gulden Lomberg Chem Fab | Nitrofuryl-pyrazole derivatives methods for producing them and medicaments comprising them |
| ZA807267B (en) * | 1979-11-26 | 1981-11-25 | Sterling Drug Inc | 5-(pyridinyl)-2(1h)-pyridinones,useful as cardiotonic agents and their preparation |
| US4271168A (en) * | 1979-12-26 | 1981-06-02 | Sterling Drug Inc. | Selected 3-acylamino-5-[4(or 3)-pyridinyl]-2(1H)-pyridinones |
| ZA821818B (en) * | 1981-03-30 | 1983-02-23 | Sterling Drug Inc | 3-amino-5-(substituted)-2 (1h)-pyridinones and 3-cyano compounds useful as cardiotonics and preparation thereof |
-
1983
- 1983-05-06 BE BE1/10783A patent/BE896678A/en not_active IP Right Cessation
- 1983-05-17 JP JP58086527A patent/JPS58213759A/en active Granted
- 1983-05-18 ZA ZA833584A patent/ZA833584B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA833584B (en) | 1984-12-24 |
| JPS58213759A (en) | 1983-12-12 |
| BE896678A (en) | 1983-11-07 |
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