JPS5970667A - 1,4-dihydropyridine derivative - Google Patents
1,4-dihydropyridine derivativeInfo
- Publication number
- JPS5970667A JPS5970667A JP57180616A JP18061682A JPS5970667A JP S5970667 A JPS5970667 A JP S5970667A JP 57180616 A JP57180616 A JP 57180616A JP 18061682 A JP18061682 A JP 18061682A JP S5970667 A JPS5970667 A JP S5970667A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- phosphorus
- compound expressed
- melting point
- 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
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- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は融点が196〜202℃である2、6−シメチ
ルー4−(3−ニトロフェニル)−1,4−ジヒドロピ
リジン−3,5−ジカルボン酸−3−(1−ベンジル−
3−ピペリジル)エステル−5−メチルエステルおよび
その塩に関する。Detailed Description of the Invention The present invention provides 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(1- benzyl
3-piperidyl) ester-5-methyl ester and its salt.
本化合物は血圧降下作用、冠血管拡張作用、末梢血管拡
張作用などを有し、血圧降下剤、血管拡張剤などの循環
器官用薬として有用な化合物である。This compound has antihypertensive effects, coronary vasodilatory effects, peripheral vasodilatory effects, etc., and is a useful compound as a circulatory organ drug such as an antihypertensive agent and a vasodilator.
以下に本発明の詳細な説明する。The present invention will be explained in detail below.
本化合物の製造工程の一例は吹の通りである。An example of the manufacturing process for the present compound is as follows.
目的化合物
化合物■は、化合物「とハロゲン化試薬(例えば、塩化
チオニル、三塩化リン、五塩化リン、オキシ塩化リン、
三臭化リン等)との反応によシ得られる。The target compound compound ■ is a combination of a compound "and a halogenating reagent (e.g., thionyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride,
It is obtained by reaction with phosphorus tribromide, etc.).
反応はジクロルメタン、クロロホルム、四塩化炭素、ク
ロルベンゼン等のノ・ロゲン化炭化水素類、ベンゼン、
トルエン等の芳香族炭化水素類、テトラヒドロフラン、
ジオキサン等のエーテル類、アセトニトリル、FbN−
ジメチルホルムアミド、ヘキサメチルホスホリックトリ
アミド等の非プロトン性極性溶媒、ピリジン、トリエチ
ルアミン等のアミン類の存在下または非存在下に行われ
るが、特に塩化チオニルをハロゲン化試薬として用い、
N、N−ジメチルホルムアミドまたはへキサメチルホス
ホリックトリアミドの存在下、上記の溶媒を併用または
併用せずして行われる。The reaction is carried out with dichloromethane, chloroform, carbon tetrachloride, chlorobenzene, etc., benzene,
Aromatic hydrocarbons such as toluene, tetrahydrofuran,
Ethers such as dioxane, acetonitrile, FbN-
It is carried out in the presence or absence of an aprotic polar solvent such as dimethylformamide or hexamethylphosphoric triamide, or an amine such as pyridine or triethylamine, but in particular using thionyl chloride as a halogenating reagent,
It is carried out in the presence of N,N-dimethylformamide or hexamethylphosphoric triamide, with or without the above-mentioned solvents.
カルボン酸と塩化チオニルのモル比は1.0 : 0.
8〜1.0:2.0の範囲、好ましくは!、0:0.9
〜1.0:1.2である。The molar ratio of carboxylic acid and thionyl chloride is 1.0:0.
A range of 8 to 1.0:2.0, preferably! ,0:0.9
~1.0:1.2.
塩化チオニルとN、N−ジメチルホルムアミド、または
へキサメチルホスホリックトリアミドのモル比は、1:
1〜1 : 100好壕しくは1:5〜1:50である
。The molar ratio of thionyl chloride and N,N-dimethylformamide or hexamethylphosphoric triamide is 1:
1 to 1:100 or preferably 1:5 to 1:50.
反応は一70℃〜100℃、好ましくは一20℃〜50
℃の温度で行われる。The reaction is carried out at -70°C to 100°C, preferably -20°C to 50°C.
It is carried out at a temperature of °C.
次いで、得られた化合物■(単離しなくともよい)と化
合物■とを反応させることによシ目的化合物が得られる
。溶媒としては、化合物■から化合物■を製造する際に
使用された溶媒が用いられる。Next, the desired compound is obtained by reacting the obtained compound (1) (which does not need to be isolated) with compound (2). As the solvent, the solvent used in producing compound (2) from compound (1) is used.
反応は、化合物■と化合物■とのモル比1.0=0.8
〜1.0:2.0好ましくは1.0〜0.9〜1.0=
1.2の範囲で、−70℃〜100℃好ましくは一20
℃〜50℃の温度で行われる。The reaction takes place at a molar ratio of compound (1) and compound (2) of 1.0 = 0.8.
~1.0:2.0 preferably 1.0-0.9-1.0=
1.2 in the range of -70°C to 100°C, preferably -20°C
It is carried out at a temperature of 50°C to 50°C.
反応液中には、2.6−シメチルー4−(3−ニトロフ
ェニル)−1,4−ジヒドロピリジン−3,5−ジカル
ボン酸−3−(l−ベンジル−3−ピペリジル)エステ
ル−5−メチルエステルの融点196〜202°Cの化
合物(α体)と融点236〜242℃の化合物(β体)
との混合物が存在するので、目的化合物であるα体を単
離するのには次の如く行なう。In the reaction solution, 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(l-benzyl-3-piperidyl) ester-5-methyl ester A compound with a melting point of 196 to 202°C (α form) and a compound with a melting point of 236 to 242°C (β form)
Since a mixture of the α-form and the target compound exists, the α-isomer, which is the target compound, can be isolated as follows.
反応液を抽出、濃縮、カラムクロマトグラフィー等の通
常の操作の後、塩化水素ガス、または適当な溶媒に溶か
した塩化水素溶液を加えて塩酸塩とし、必要に応じてそ
の溶媒を除去した後、適当な単一または混合溶媒から分
別結晶を行えばα体が晶出し、β体は溶液中に残る。After the reaction solution is subjected to normal operations such as extraction, concentration, and column chromatography, hydrogen chloride gas or a hydrogen chloride solution dissolved in an appropriate solvent is added to form a hydrochloride salt, and after removing the solvent as necessary, If fractional crystallization is carried out from an appropriate single or mixed solvent, the α-isomer will crystallize and the β-isomer will remain in the solution.
分別結晶に適当な単一または混合溶媒としてハ、エタノ
ール、クロロホルム、エタノール−アセトン、クロロホ
ルム−アセトン、クロロホルム−エーテル、クロロホル
ム−酢酸エチル等があげられ、特にエタノール−アセト
ン、クロロホルム−アセトンの混合溶媒が好ましい。Suitable single or mixed solvents for fractional crystallization include ethanol, chloroform, ethanol-acetone, chloroform-acetone, chloroform-ether, chloroform-ethyl acetate, etc. Especially mixed solvents of ethanol-acetone and chloroform-acetone are used. preferable.
尚、出発原料である化合物…は、文献既知〔T。In addition, the starting material compound... is known from the literature [T.
Shibanuma e t al、、Chem、ph
arm、 Bull、 # 28 e2809(198
0))の化合物であり、次に示す反応式によって得られ
る。Shibanuma et al,, Chem, ph
arm, Bull, #28 e2809 (198
0)) and is obtained by the reaction formula shown below.
CH、oc 2T(。CH, oc 2T(.
しM 21JX+z tlB
化合物■
本化合物の塩としては、塩酸塩、臭化水素酸塩、りん、
代塩、硫酸塩などの無機酸塩、ぎ酸塩、酢酸塩、フマル
酸塩、マレイン酸塩、リンゴ酸塩などの有機酸塩があげ
られる。ShiM 21JX+z tlB Compound■ Salts of this compound include hydrochloride, hydrobromide, phosphorus,
Examples include inorganic acid salts such as substitute salts and sulfates, and organic acid salts such as formates, acetates, fumarates, maleates, and malates.
次に本化合物の血μ降下作用を説明する。Next, the blood μ-lowering effect of this compound will be explained.
試験方法
雑種成犬(s−xsKp)をベンドパルビタール・ナト
リウムs o mgAg−の静脈内投与によシ麻酔した
。左太腿動脈にカニユーレを挿入し、圧カドランスジュ
ーサー(日本光電)によシ、血圧を測定してポリグラフ
に記録した。Test Method Adult mongrel dogs (s-xsKp) were anesthetized by intravenous administration of bendoparbital sodium somgAg. A cannula was inserted into the left femoral artery, and blood pressure was measured using a pressure cadence juicer (Nihon Kohden) and recorded on a polygraph.
その結果を第1表に示す。The results are shown in Table 1.
第1表
第1表に示したようにα体は投与後1分から明らかな血
圧降下作用を発現し、90分以上持続した。As shown in Table 1, the α form exerted a clear blood pressure lowering effect from 1 minute after administration and lasted for more than 90 minutes.
試験方法
雑犬(9−tsKp)をチオベンタール・ナトリウム麻
酔下左腎動脈を狭窄し、腎性高血圧犬を作成した。左頚
動脈から下行動脈内に挿入したポリエチレンカニユーレ
(頚背部に固定)を介し、無麻酔下、血圧変化を観照的
に測定した。Test method A mongrel dog (9-tsKp) was anesthetized with thiobental sodium and the left renal artery was constricted to create a dog with renal hypertension. Changes in blood pressure were measured visually without anesthesia via a polyethylene cannula (fixed to the back of the neck) inserted into the descending artery from the left carotid artery.
薬物ハ、o、a%カルボキシメチルセルロースに懸濁し
たものを体重I Kgあたり0.5rn1.経口投与用
チューブを用いて経口投与した。The drug was suspended in O, A% carboxymethylcellulose at a dose of 0.5rn1.0 per kg of body weight. It was administered orally using an oral administration tube.
その結果を第2表に示す。The results are shown in Table 2.
第2表
第2表(続き)
注)使用薬物;α体
本発明化合物は、その薬理作用にかんがみて、投与目的
に対する各種の製薬形態で使用可能であり、特に、錠剤
、散剤などの経口服用形態として用いるのが好ましい。Table 2 Table 2 (Continued) Note) Drugs used: α-form The compound of the present invention can be used in various pharmaceutical forms for the purpose of administration, in view of its pharmacological action. It is preferable to use it as a form.
錠剤の場合は一錠中に本発明化合物を5〜30%(w/
w)含有せしめればよい。その他の成分(担体)として
は通常用いられる賦形剤、崩壊剤、滑沢剤、結合剤、剤
皮剤等が用いられる。In the case of tablets, each tablet contains 5 to 30% (w/
w) It is sufficient if it is contained. Other components (carriers) include commonly used excipients, disintegrants, lubricants, binders, coating agents, and the like.
賦形剤としてはブドウ類、乳糖等、崩壊剤としてハテン
ブン、カルボキシメチルセルロースカルシウム等、滑沢
剤としてはステアリン酸マグネシウム、タルク等、結合
剤としては単シロップ、ポリビニルアルコール、ゼラチ
ン、ヒドロキシプ四ピルセルロース等、剤皮剤としては
分散剤と可塑剤があげられるが、分散剤としてハメチル
セルロース、エチルセルロース等、可塑剤としてはグリ
セリン、ポリエチレングリコール等が用いられる。また
結晶セルリースは崩壊、結合および賦形剤としての性質
をすべて有するものとして使用される。Excipients include grapes, lactose, etc. Disintegrants include Hatenbun, carboxymethyl cellulose calcium, etc. Lubricants include magnesium stearate, talc, etc. Binders include monosyrup, polyvinyl alcohol, gelatin, and hydroxypyl cellulose. Examples of coating agents include dispersants and plasticizers, and examples of dispersants include hamethyl cellulose and ethyl cellulose, and examples of plasticizers include glycerin and polyethylene glycol. Moreover, crystalline cellulose is used as having all the properties of disintegration, binding, and excipient.
散剤の場合は本発明化合物を1〜20%(w/w )含
有せしめればよい。担体としてはブドウ糖、乳糖等の賦
形剤、ヒドロキシグロビルセルロース等の結合剤等が用
いられる。本発明化合物(α体)の雄ラット経口投与に
おけるLD、。In the case of a powder, the compound of the present invention may be contained in an amount of 1 to 20% (w/w). As carriers, excipients such as glucose and lactose, binders such as hydroxyglobil cellulose, etc. are used. LD in oral administration of the compound of the present invention (α form) to male rats.
は127吟勺である。投与量は成人(約60Ky)1日
あた#)t−10011Fの範囲が好ましい。is 127 gin. The dosage is preferably in the range of #) t-10011F per day for adults (approximately 60 Ky).
実施例1
2.6−シメチルー4−(3−ニトロフェニル)−1,
4−ジヒドロピリジン−3,5−ジカルボン酸モノメチ
ルエステルio、oorをジクロルメタンとN、N−ジ
メチルホルムアミドの混合溶媒(4: I V/V )
70 rnlにMl1mシ、水冷下ニ塩化チオニル2
.43 mlを加えた。1時間水冷攪拌後、1−ベンジ
ル−3−ヒドロキシピペリジン6.331を加え、さら
に水冷攪拌した。2,5時間反応後、該反応液を水10
0m1/、次いで食塩水100肩lで洗かし、ジクロル
メタン層を無水硫酸ナトリウムで乾燥後、減圧濃縮した
。その後、該濃縮液にアセトン100*/とエタノール
8alt#nえて、黄色の2.6−シメチルー4−(3
−ニトロフェニル)−’1.4−シヒドロヒリシンー3
,5−ジカルボン酸−3−(1−ベンジル−3−ピペリ
ジル)エステル−5−メチルエステル塩酸塩(α体)
7.57 tyを得だ。融点197−198℃(エタノ
ール)。Example 1 2.6-dimethyl-4-(3-nitrophenyl)-1,
4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester io, oor in a mixed solvent of dichloromethane and N,N-dimethylformamide (4: IV/V)
Add 1 m of ml to 70 rnl and add 2 ml of thionyl dichloride under water cooling.
.. 43 ml was added. After stirring under water cooling for 1 hour, 6.331 g of 1-benzyl-3-hydroxypiperidine was added, and the mixture was further stirred under water cooling. After reacting for 2.5 hours, the reaction solution was diluted with 10 ml of water.
The dichloromethane layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Then, acetone 100*/ and ethanol 8 alt#n were added to the concentrated solution, and yellow 2,6-dimethyl-4-(3
-nitrophenyl)-'1,4-cyhydrohyricin-3
, 5-dicarboxylic acid-3-(1-benzyl-3-piperidyl) ester-5-methyl ester hydrochloride (α form)
Got 7.57 ty. Melting point 197-198°C (ethanol).
またその結晶母液からβ体5.21fを得た。Further, β-isomer 5.21f was obtained from the crystal mother liquor.
融点239−240℃(エタノール−メタノール) α体の物性値を以下に示す。Melting point 239-240℃ (ethanol-methanol) The physical properties of the α-form are shown below.
IR(KBr、cmカニ1680.152511345
NMR(DMSO−δ) : 1.3−12 (4H,
broad、)、 2.33 (6H。IR (KBr, cm crab 1680.152511345
NMR (DMSO-δ): 1.3-12 (4H,
broad, ), 2.33 (6H.
s)、 2.7−3.4()L broad)*
L57(3L 8 )+4.40(2H* 8)14
.98(IHI S)15.20(IHy 8%7.3
−8.2 (9H+ m )* 9.47 (I H,
broad)計算値C%) 62.04 5.9
6 7.75特許出願人 (102)wJJ和醗酵工
業株式会社代表者 本 下 祝 部ハ’t:、1:i’
;::Nl:”B手続補正書
昭和58年1月2q日
1、事件の表示
昭和57年特許願第180616号
2、発明の名称
1.4−ジヒドロピリジン誘導体
3、補正をする者
事件との関係 特許出願人
郵便番号 100
住 所 東京都千代田区大手町−丁目6番1号名称
(102) VIJfI+醗酵工業株式会社(置:03
−201−7211内線2751 )代表者 木 下
祝 部7パ□・
1−9H+1
覧、゛、・1 、。s), 2.7-3.4()L broad)*
L57 (3L 8) + 4.40 (2H* 8) 14
.. 98 (IHI S) 15.20 (IHy 8% 7.3
-8.2 (9H+m)*9.47 (I H,
broad) Calculated value C%) 62.04 5.9
6 7.75 Patent Applicant (102) wJJ Wafunko Kogyo Co., Ltd. Representative Honshita Ikube H't:, 1:i'
;::Nl:” B Procedural Amendment January 2q, 1982 1, Description of the case 1982 Patent Application No. 180616 2, Title of the invention 1, 4-dihydropyridine derivative 3, Person making the amendment Related Patent applicant postal code 100 Address 6-1 Otemachi, Chiyoda-ku, Tokyo Name
(102) VIJfI+Hakko Kogyo Co., Ltd. (Location: 03
-201-7211 extension 2751) Representative Kinoshita
Celebration Part 7 Part □・1-9H+1 View, ゛,・1,.
4、補正の対象 、、+:
、、T、、、5:、7/明細奸の特許請求の範囲および
発明の詳細な説明の(閘
[別紙の辿り1
+21 明#ll1it第1 N下9 行「本発明は
融点が」を
「本発明は塩酸塩の融点が−lに訂正する。4. Target of correction ,,+:
,,T,,,5:,7/Specific claims and detailed description of the invention "The present invention corrects the melting point of the hydrochloride to -1.
(3)同書@4頁6行 11.0〜0.9」をrt、o:o、9」に訂正する。(3) Same book @ page 4, line 6 11.0-0.9" is corrected to rt, o:o, 9".
(4)同書¥J4頁下4行−第5頁1行[反応液を抽出
、濃縮、カラムクロマトグラフィー等の通常の操作の後
、塩化水素ガス、または適当な溶媒に溶かした塩化水素
溶液を加えて塩酸塩とし、必要に応じてその溶媒を除去
した後、適当な単一−1を
「反応液を抽出、濃縮等の通常の操作の後、適当な単一
」に訂正する。(4) Ibid.¥J, page 4, bottom line 4 - page 5, line 1 In addition, after converting into a hydrochloride salt and removing the solvent if necessary, correct the appropriate single-1 to ``After the reaction solution is subjected to normal operations such as extraction and concentration, an appropriate single''.
(5)同市゛第6頁下1および2行の間に次の文章を加
入する。(5) Add the following sentence between the first and second lines of the bottom of page 6 of the city.
「薬物は、ポリエチレングリコール400に溶解して、
体重I KPあたりQ、’1mlを上腕静脈よシ投与し
た。」
特許請求の範囲
塩酸塩の融点が196〜202℃である2、6−シメチ
ルー4−(3−ニトロフェニル)−1,4−ジヒドロピ
リジン−3,5−ジカルボン酸−3−(1−ベンジル−
3−ピペリジル)エステル−5−メチルエステルおよび
その塩っ
手続補正書
昭和58年2月22日
特許庁長官 殿
1、事件の表示
昭和57年特許願第180616号
2、発明の名称
1、4〜ジヒドロピリジン誘導体
3、補正をする者
事件との関係 特許出願人
郵便番号 100
住 所 東京都千代田区大手町−丁目6番1号名称 (
102)協和醗酵工業株式会社(置 : 03−201
−7211内線2751)明細書の発明の詳細な説明の
欄 。"The drug is dissolved in polyethylene glycol 400,
1 ml of Q per body weight I KP was administered into the brachial vein. ” Claims 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-(1-benzyl-
3-Piperidyl) ester-5-methyl ester and its salts Procedural amendment February 22, 1980 Commissioner of the Japan Patent Office 1. Indication of the case 1980 Patent Application No. 180616 2. Title of the invention 1, 4- Dihydropyridine Derivatives 3, Relationship with the Person Making Amendment Case Patent Applicant Postal Code 100 Address 6-1 Otemachi-chome, Chiyoda-ku, Tokyo Name (
102) Kyowa Hakko Kogyo Co., Ltd. (Location: 03-201
-7211 extension 2751) Detailed description of the invention in the specification.
5、補正の内容 (1) 明細書第4頁13行 「の融点」を「の塩酸塩の融点」に訂正する。5. Contents of correction (1) Page 4, line 13 of the specification Correct "melting point of" to "melting point of hydrochloride of".
−→F 続ン市 I]三 Y翳
1ノj1和58年9月t6臼
特S7庁長h゛1〜
1 事件の表示
1!(和57)口、胃1期1第180616号2 発明
の名称
1、/l−ジヒド[]ピリジン誘導体
3 補正をηる石
事ftどの関係 1gJ r出願人
郵便番舅 100
fJ所 東Qil千代田区人千町−J目6番1号名称
<102)協和醗酵工業株式会社(]]1川−:03−
201−7211内線27!11>5 補正の内容
i ) ITJJlrnm第12L412行INM1
<(DMSO−6) Jをf N M R(DtvlS
O−(16,δ)jに訂正り°る。-→F Zokuin City I] 3 Y 1 no j 1 September 1958 t 6 Usutoku S7 Director h゛ 1 ~ 1 Incident display 1! (Japanese 57) Mouth, Stomach 1 Period 1 No. 180616 2 Name of the invention 1, /l-dihydro[]pyridine derivative 3 Correlation between amendments 1gJ r Applicant postal code 100 fJ Office Higashi Qil Chiyoda Ward Sencho - J number 6 number 1 name
<102) Kyowa Hakko Kogyo Co., Ltd. (]] Ichikawa-:03-
201-7211 extension 27!11>5 Correction details i) ITJJlrnm line 12L412 INM1
<(DMSO-6) J f N M R (DtvlS
Correct it to O-(16, δ)j.
2) 同書第′12貞14行
15、20 (1N、 s )JをI’5.20(11
−1,broad ) Jに訂正りる。2) Same book No. 12, line 14, 15, 20 (1N, s) J to I'5.20 (11
-1, broad) Corrected to J.
Claims (1)
(3−ニトロフェニル)−1,4−ジヒドロピリジ、/
−3,5−ジカルボン酸−3−(1−イソシル−3−
ピペリジル)エステル−5−メチルエステルおよびその
塩。2,6-dimethyl-4- having a melting point of 196-202°C
(3-nitrophenyl)-1,4-dihydropyridi, /
-3,5-dicarboxylic acid-3-(1-isosyl-3-
piperidyl) ester-5-methyl ester and its salts.
Priority Applications (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57180616A JPS5970667A (en) | 1982-10-15 | 1982-10-15 | 1,4-dihydropyridine derivative |
EP19830109968 EP0106275B1 (en) | 1982-10-15 | 1983-10-05 | 1,4-dihydropyridine derivatives |
AU19898/83A AU557175B2 (en) | 1982-10-15 | 1983-10-05 | 2,6-dimethyl-4-(3-nitro phenyl)-1,4-dihydro pyridine-3,5- dicarboxylic acid esters |
AT83109968T ATE61579T1 (en) | 1982-10-15 | 1983-10-05 | 1,4-DIHYDROPYRIDINE DERIVATIVES. |
DE8383109968T DE3382204D1 (en) | 1982-10-15 | 1983-10-05 | 1,4-DIHYDROPYRIDINE DERIVATIVES. |
ES526441A ES526441A0 (en) | 1982-10-15 | 1983-10-13 | A PROCEDURE FOR PRODUCING 2,6-DIMETHYL-4- (3NITROPHENIL) -1,4-DIHIDROPIRIDIN 3,5-DICARBOXILATO DE 1, BENCIL-3-PIPERIDILO AND METHYL AND ITS HYDROCHLORIDE. |
MX199109A MX156034A (en) | 1982-10-15 | 1983-10-14 | PROCEDURE FOR PREPARING 3-ESTER- (IBENCIL-3-PIPERIDIL) -5-METHYL-ESTER, FROM ACID 2,6-DIMETIL-4- (3-NITROFENIL) -1,4-DIHIDROPIRIDIN-3,5-DICARBOXILICO |
CA000438995A CA1246078A (en) | 1982-10-15 | 1983-10-14 | ( )-2,6-dimethyl-4-(3-nitrophenil)-1,4- dihydropyridine-3,5-decarboxylicacid-3-(1-benzyl-3- piperidyl)ester-5-methylester |
KR1019830004886A KR860001946B1 (en) | 1982-10-15 | 1983-10-15 | Process for preparing 1,4-dihydropyridine derivatives |
KR1019860008104A KR860001950B1 (en) | 1982-10-15 | 1986-09-27 | Process for preparing 1,4-dihydropyridine derivatives |
KR1019860008103A KR860001949B1 (en) | 1982-10-15 | 1986-09-27 | Process for preparing 1,4-dihydropyridine derivatives |
KR1019860008102A KR860001948B1 (en) | 1982-10-15 | 1986-09-27 | Process for preparing 1,4-dihydropyridine derivatives |
KR1019860008105A KR860001951B1 (en) | 1982-10-15 | 1986-09-27 | Process for preparing 1,4-dihydropyridine derivatives |
KR1019860008101A KR860001947B1 (en) | 1982-10-15 | 1986-10-15 | Process for preparing 1,4-dihydropyridine derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57180616A JPS5970667A (en) | 1982-10-15 | 1982-10-15 | 1,4-dihydropyridine derivative |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP20323186A Division JPS62174017A (en) | 1986-08-29 | 1986-08-29 | 1,4-dihydropyridine derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS5970667A true JPS5970667A (en) | 1984-04-21 |
Family
ID=16086338
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP57180616A Pending JPS5970667A (en) | 1982-10-15 | 1982-10-15 | 1,4-dihydropyridine derivative |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5970667A (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS59225162A (en) * | 1983-06-03 | 1984-12-18 | Kyowa Hakko Kogyo Co Ltd | 1,4-dihydropyridine derivative |
JPS61260064A (en) * | 1985-05-14 | 1986-11-18 | Kyowa Hakko Kogyo Co Ltd | Dihydropyridine derivative |
US6739160B1 (en) | 1998-01-19 | 2004-05-25 | Asahi Kasei Kabushiki Kaisha | Lint-free wiper |
JP2013520520A (en) * | 2011-04-18 | 2013-06-06 | ヘフェイ ベイニ メディカル テクノロジー カンパニー リミテッド | Benidipine hydrochloride nanoparticles and preparation method thereof |
JP2014511881A (en) * | 2011-04-18 | 2014-05-19 | ヘフェイ ベイニ メディカル テクノロジー カンパニー リミテッド | Method for preparing high-purity benidipine hydrochloride |
Citations (9)
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US2802007A (en) * | 1954-05-24 | 1957-08-06 | Lakeside Lab Inc | Method of reducing 3-hydroxypyridine and its derivatives |
US2987517A (en) * | 1954-04-20 | 1961-06-06 | Cilag Chemie | Alpha aryl-3-methyl-pentanoic acid-nu-lower alkyl heterocyclic esters |
JPS504652A (en) * | 1972-09-13 | 1975-01-18 | ||
JPS5024277A (en) * | 1972-04-18 | 1975-03-15 | ||
JPS5392784A (en) * | 1976-12-30 | 1978-08-15 | Nattermann A & Cie | 1*44dihydropyridine derivative and vasolidator drugs containing same |
JPS55301A (en) * | 1978-02-14 | 1980-01-05 | Yamanouchi Pharmaceut Co Ltd | 1,4-dihydropyridine-3,5-dicarboxylic ester derivative and its preparation |
JPS5636455A (en) * | 1979-09-01 | 1981-04-09 | Bayer Ag | Novel optically active 1*44dihydropyridine compound* its manufacture and its medicinal use |
JPS5762257A (en) * | 1980-10-03 | 1982-04-15 | Yoshitomi Pharmaceut Ind Ltd | 1,4-dihydropyridine-3,5-dicarboxylic acid ester or its salt |
JPS57171968A (en) * | 1981-04-17 | 1982-10-22 | Kyowa Hakko Kogyo Co Ltd | 1,4-dihydropyridine derivative |
-
1982
- 1982-10-15 JP JP57180616A patent/JPS5970667A/en active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2987517A (en) * | 1954-04-20 | 1961-06-06 | Cilag Chemie | Alpha aryl-3-methyl-pentanoic acid-nu-lower alkyl heterocyclic esters |
US2802007A (en) * | 1954-05-24 | 1957-08-06 | Lakeside Lab Inc | Method of reducing 3-hydroxypyridine and its derivatives |
JPS5024277A (en) * | 1972-04-18 | 1975-03-15 | ||
JPS504652A (en) * | 1972-09-13 | 1975-01-18 | ||
JPS5392784A (en) * | 1976-12-30 | 1978-08-15 | Nattermann A & Cie | 1*44dihydropyridine derivative and vasolidator drugs containing same |
JPS55301A (en) * | 1978-02-14 | 1980-01-05 | Yamanouchi Pharmaceut Co Ltd | 1,4-dihydropyridine-3,5-dicarboxylic ester derivative and its preparation |
JPS5636455A (en) * | 1979-09-01 | 1981-04-09 | Bayer Ag | Novel optically active 1*44dihydropyridine compound* its manufacture and its medicinal use |
JPS5762257A (en) * | 1980-10-03 | 1982-04-15 | Yoshitomi Pharmaceut Ind Ltd | 1,4-dihydropyridine-3,5-dicarboxylic acid ester or its salt |
JPS57171968A (en) * | 1981-04-17 | 1982-10-22 | Kyowa Hakko Kogyo Co Ltd | 1,4-dihydropyridine derivative |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS59225162A (en) * | 1983-06-03 | 1984-12-18 | Kyowa Hakko Kogyo Co Ltd | 1,4-dihydropyridine derivative |
JPS61260064A (en) * | 1985-05-14 | 1986-11-18 | Kyowa Hakko Kogyo Co Ltd | Dihydropyridine derivative |
US6739160B1 (en) | 1998-01-19 | 2004-05-25 | Asahi Kasei Kabushiki Kaisha | Lint-free wiper |
JP2013520520A (en) * | 2011-04-18 | 2013-06-06 | ヘフェイ ベイニ メディカル テクノロジー カンパニー リミテッド | Benidipine hydrochloride nanoparticles and preparation method thereof |
JP2014511881A (en) * | 2011-04-18 | 2014-05-19 | ヘフェイ ベイニ メディカル テクノロジー カンパニー リミテッド | Method for preparing high-purity benidipine hydrochloride |
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