JPH03151362A - 1,4-dihydropyridine compound - Google Patents
1,4-dihydropyridine compoundInfo
- Publication number
- JPH03151362A JPH03151362A JP28844389A JP28844389A JPH03151362A JP H03151362 A JPH03151362 A JP H03151362A JP 28844389 A JP28844389 A JP 28844389A JP 28844389 A JP28844389 A JP 28844389A JP H03151362 A JPH03151362 A JP H03151362A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- compound
- dihydropyridine
- substituent
- 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 1,4-dihydropyridine compound Chemical class 0.000 title claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 125000005462 imide group Chemical group 0.000 claims 1
- 150000003949 imides Chemical group 0.000 abstract description 2
- 206010067482 No adverse event Diseases 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 239000002220 antihypertensive agent Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000036772 blood pressure Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-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
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 210000002376 aorta thoracic Anatomy 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 206010060800 Hot flush Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000001964 calcium overload Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- JDUFEJZCRZDGLG-UHFFFAOYSA-N diethyl 2,6-dimethyl-1-phenyl-4H-pyridine-3,5-dicarboxylate Chemical class C1(=CC=CC=C1)N1C(=C(CC(=C1C)C(=O)OCC)C(=O)OCC)C JDUFEJZCRZDGLG-UHFFFAOYSA-N 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 229910001868 water Inorganic materials 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
この発明は、筋の収縮に関係するＣａの流れに影響を及
ぼず薬物として知られている１、４−ジヒドロピリジン
ン類の新規化合物を提供するものであり、その化合物は
血圧を降下させる作用を持っている。Detailed Description of the Invention (Industrial Application Field) The present invention provides a novel compound of 1,4-dihydropyridine class, which does not affect the flow of Ca related to muscle contraction and is known as a drug. This compound has the effect of lowering blood pressure.
（従来の技術）
１．４−ジヒドロピリジン化合物の中、４−二トロ置換
フェニル−２，６−シメチルー１．４−ジヒドロピリジ
ン−３，５−ジカルボン酸ジエチＪレエステルが１８８
７年に公知となっている。（Ｃｈｅｍ、Ｂｅ ｒ、Ｖｏ
１．２０）
一般名二７ニジピンとして知られている４−（２ニトロ
フエニル）−２，６−シメチルー１゜４−ジヒドロピリ
ジン−３，５−ジカルボン酸ジメチルエステルが冠血管
拡張作用、全抹消血管抵抗の減少、抗高血圧作用、心筋
酸素需要のバランス改善、細胞内Ｃａ過負荷による動脈
壁へのＣａ沈着抑制作用を示す薬剤として疾病の治療に
使用されている。更に、この薬物と構造類似の化合物で
、一般名塩酸二カルジピンと呼ばれている４−（３′−
二トロフェニル）−２，６−シメチルー１．４−ジヒド
ロピリジン−３，５−ジカルボン酸−３−メチルエステ
ル−５−１−ＣＮ−ベンジル−Ｎ−メチルアミノ）エチ
ルエステル塩酸塩が冠血管、脳血管の拡張作用を示し、
脳血流障害、高血圧症の治療に使用されている。しかし
ながら時に、頻脈、発汗、頭痛、のぼせ、めまい、どう
き等の好ましくない副作用が現れることがあり、主作用
を、投与後できるだけ長時間持続させ、副作用を少なく
した化合物をみつけだすために、数多くの化合物が合成
され、活性測定試験に供せられ、試行錯誤を繰り返しな
がら、より優れた化合物の創製が行われている現状にあ
る。(Prior art) Among 1,4-dihydropyridine compounds, 4-ditro-substituted phenyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester is 188
It became publicly known in 1972. (Chem, Be r, Vo
1.20) 4-(2nitrophenyl)-2,6-dimethyl-1゜4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester, commonly known as 27nidipine, has a coronary vasodilatory effect and a total peripheral vascular resistance. It is used in the treatment of diseases as a drug that exhibits antihypertensive effects, improves the balance of myocardial oxygen demand, and suppresses Ca deposition on arterial walls due to intracellular Ca overload. Furthermore, a compound with a similar structure to this drug, 4-(3'-
ditrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methyl ester-5-1-CN-benzyl-N-methylamino)ethyl ester hydrochloride in coronary blood vessels, brain Shows blood vessel dilation effect,
It is used to treat cerebral blood flow disorders and hypertension. However, sometimes undesirable side effects such as tachycardia, sweating, headache, hot flashes, dizziness, and palpitations may occur.In order to find a compound that maintains its main effect for as long as possible after administration and has fewer side effects, a number of studies have been conducted. At present, compounds have been synthesized and subjected to activity measurement tests, and through repeated trial and error, better compounds are being created.
（本発明が解決しようとする問題点）
本発明は、式（Ｉ）で示される新しい１，４−ジヒドロ
ピリジン化合物を提供せんとするものである。即ち、
式
（式中Ａは置換基を有しているフェニル基、Ｒ３は炭素
数１から５の直鎖若しくは分岐鎖の飽和又は不飽和アル
キルオキシ基であって、該基はハロゲン、水酸基、アリ
ール基、ヘテロ飽和又は不飽和環化合物で置換されても
よい。また、Ｒ２はアラルキルチオ基、若しくは
Ｂ−Ｎ−Ｒ’
７
（Ｂは炭素数２から５の分岐していてもよいアルキレン
基を、Ｒ６，Ｒ７は同−又は異なりて水素。(Problems to be Solved by the Present Invention) The present invention seeks to provide a new 1,4-dihydropyridine compound represented by formula (I). That is, the formula (where A is a phenyl group having a substituent, R3 is a linear or branched saturated or unsaturated alkyloxy group having 1 to 5 carbon atoms, and the group is a halogen, a hydroxyl group, It may be substituted with an aryl group, a heterosaturated or unsaturated ring compound.In addition, R2 is an aralkylthio group, or B-N-R'7 (B is an optionally branched alkylene group having 2 to 5 carbon atoms). , R6 and R7 are the same or different and are hydrogen.
アルキル基、置換基を有しても良いアラルキル基。Alkyl group, aralkyl group which may have a substituent.
アシル基、置換基を有しても良いアロイル基であるか又
は一方がＢと共に環を形成していても良い。It may be an acyl group, an aroyl group which may have a substituent, or one of them may form a ring with B.
又、Ｒ＠、Ｒ１はＮと共にイミド環を成していてもよい
。）Ｒ’、Ｒ’は同−又は異なりて低級アルキル基を示
す。）
で示される１、４−ジヒドロピリジン化合物及びその塩
が提供される。Further, R@ and R1 may form an imide ring together with N. ) R' and R' are the same or different and represent a lower alkyl group. ) A 1,4-dihydropyridine compound and a salt thereof are provided.
（問題点を解決するための手段）
本発明が提供する上記式（Ｉ）で示される化合物は次の
ようにして造られる。(Means for Solving the Problems) The compound represented by the above formula (I) provided by the present invention is produced as follows.
−ＣＨ０ で示されるアルデヒド化合物と ＮＨ。-CH0 The aldehyde compound represented by N.H.
ＣＨ３Ｃ−ＣＨＣ０ＯＲ’ 及び
ＯＯ
Ｉ７ Ｉ＋
Ｒ” ＯＣＣＨｚ ＣＣＨ！ ＣＯＯＲ３或は、上記ア
ルデヒド化合物と
ＯＮＨ２
とを反応させることによって造られる。CH3C-CHC0OR' and OO I7 I+ R''OCCHz CCH! COOR3 or produced by reacting the above aldehyde compound with ONH2.
（式中Ａ、Ｒ”、Ｒ３，Ｒ’ｌｉ前記と同ｃ。）反応は
、溶媒の存在又は不存在で、過熱撹拌することによって
行われる。用いられる溶媒としては低級アルコール、ジ
オキサン、テトラヒドロ７ラン、ベンゼン、トルエン、
キシレン、ヘキサン、ヘゲタン、オクタンなど反応に関
与しないものであれば適宜使用される。(In the formula, A, R'', R3, R'li are the same as above.) The reaction is carried out by stirring under heating in the presence or absence of a solvent. Examples of solvents used include lower alcohols, dioxane, and tetrahydro7. Ran, benzene, toluene,
Xylene, hexane, hegetane, octane, etc., which are not involved in the reaction, may be used as appropriate.
上記式（Ｉ）で示される化合物の中、Ｒ２がＯＨである
化合物はこれがメトキシ、エトキシ基である化合物を造
り、得られた化合物を加水分解して造られる。加水分解
は、苛性カリ、苛性ソーダの水、メタノール混合溶液を
用いて行われる。Among the compounds represented by the above formula (I), the compound in which R2 is OH is produced by preparing a compound in which R2 is a methoxy or ethoxy group, and then hydrolyzing the obtained compound. Hydrolysis is performed using a mixed solution of caustic potash, caustic soda, water, and methanol.
かくて得られるＲ２がＯＨである化合物を原料として各
種アルコール、メルカプタン等とエステル化反応を行い
本発明の目的化合物を得ることかでさる。ここにおいて
、エステル化反応は溶媒の存Ｉｒ立１４テ六＝−ｉ−で
ｌ＋ｌハハφｈ１−＾嬶八個φｍ１ノ＾−ｊ又は茄熱撹
拌することによって行うことができる。Using the thus obtained compound in which R2 is OH as a raw material, an esterification reaction is carried out with various alcohols, mercaptans, etc. to obtain the target compound of the present invention. Here, the esterification reaction can be carried out in the presence of a solvent in the presence of l+l φh 1-＾ 8 φm 1 ノ ＾-j or by stirring under boiling heat.
用いられる溶媒としてはピリジン、ジオキサン、テトラ
ヒドロ７ラン、ベンゼン、トルエン、キシレン、ヘキサ
ン、ヘプタン、ジメチルホルムアミド応に関与しないも
のであれば適宜使用される以下本発明を更に具体的に説
明するために実施例を記述する。The solvent to be used may be pyridine, dioxane, tetrahydroctane, benzene, toluene, xylene, hexane, heptane, dimethylformamide, etc. Any solvent that does not participate in the reaction may be used as appropriate. Describe an example.
各実施例において得た化合物は次に記載する方法で薬理
活性を測定した。The pharmacological activity of the compounds obtained in each example was measured by the method described below.
（１）ラット胸部大動脈の弛緩作用
体重３００〜４００ｇの雄性ウィスター系ラットを頚動
脈放血により致死させ、直ちに胸部大動脈を摘出した。(1) Relaxation effect on rat thoracic aorta Male Wistar rats weighing 300 to 400 g were killed by carotid artery exsanguination, and the thoracic aorta was immediately removed.
これを螺旋条片（２ｍｍＸ２０ｍｍ）標本とし、３７℃
に保温し９５％酸素と５％炭酸ガスからなる混合ガスを
通気した栄養液を２０ｍｌ満たしたマグヌス管中に０．
５ｇの張力を負荷して懸垂した。This was made into a spiral strip (2 mm x 20 mm) specimen and heated at 37°C.
A Magnus tube filled with 20 ml of nutrient solution kept warm at a temperature of 0.0 ml and a gas mixture of 95% oxygen and 5% carbon dioxide gas bubbled through it was placed in a Magnus tube.
It was suspended under a tension of 5 g.
標本を４０ｍＭのカリウム液で収縮させた後、被験化合
物を累積的に適用し弛緩度を測定し、最後に塩酸バパベ
リン（ｔｏ−’Ｍ）を適用し最大弛緩値を′求めた．、
最大弛緩値を１００％とし、５０％弛緩させるのに必要
な被験化合物の濃度（ＩＣＳ。）を累積的用量作用曲線
より算出した。After the specimen was contracted with a 40 mM potassium solution, the test compound was cumulatively applied to measure the degree of relaxation, and finally bapaverine hydrochloride (to-'M) was applied to determine the maximum relaxation value. ,
Taking the maximum relaxation value as 100%, the concentration of the test compound required to induce 50% relaxation (ICS) was calculated from the cumulative dose-response curve.
（２）ラットにおける降圧作用
体重．３００〜４００ｇの雄性ウィスター系ラットをウ
レタン麻酔（１．０ｇ／ｋｇ腹腔内投与）した。血圧は
頚動脈より圧トランスジューサーを介し測定できるよう
にセットした。被験化合物は大腿静脈に入れたカニユー
レを通し投与した。投与量はｌ ｍ ｇ ／ ｋ ｇと
した。被験化合物はＤＭＳＯ１ｍｌ中にＰＶＰ２ ００
ｍｇを含む液に溶解し、蒸留水にて希釈して調整した。(2) Antihypertensive effect body weight in rats. Male Wistar rats weighing 300-400 g were anesthetized with urethane (1.0 g/kg intraperitoneally administered). Blood pressure was set so that it could be measured via a pressure transducer from the carotid artery. Test compounds were administered through a cannula placed in the femoral vein. The dose was 1 mg/kg. The test compound was dissolved in PVP200 in 1 ml of DMSO.
The solution was dissolved in a solution containing mg, and the solution was diluted with distilled water.
投与前の血圧と投与後の最大降圧時の血圧を測定し差を
求めた（Ｍａｘ）。又最大降圧時からＭａｘの半分の値
だけ血圧が回復するまでの時間を測定した（Ｂ ｐ，。The blood pressure before administration and the blood pressure at the time of maximum blood pressure reduction after administration were measured and the difference was calculated (Max). In addition, the time from the maximum blood pressure drop until the blood pressure recovered by half of Max was measured (B p,.
）。).
実施例１
２−ヒドロキシカルボニルメチル−３．５−ジメトキシ
カルボニル−６−メチル−４− （３ ′−二トロフェ
ニル）−１．４−ジヒドロピリジン１／２クロロホルム
付加体１．５ｇ，ピリジン３ｍｌ。Example 1 1.5 g of 2-hydroxycarbonylmethyl-3.5-dimethoxycarbonyl-6-methyl-4-(3'-nitrophenyl)-1,4-dihydropyridine 1/2 chloroform adduct, 3 ml of pyridine.
Ｂ− （Ｎ−ホルミルアミノ）エタノール０．２３ｇ，
ＤＣＣｏ．８２ｇの混合物を室温で終夜撹拌した。トル
エンを加えＤＣＵを濾別し硫酸銅水溶液で洗浄、乾燥、
濃縮しシリカゲルカラムクロマトに掛けて、２−１−（
Ｎ−ホルミルアミノ）エトキシカルボニルメチル−３．
５−ジメトキシカルボニル−６−メチル−、４−（３”
−二トロフェニル）−１．４−ジヒドロピリジン（表中
実施例１の化合物）０．６４ｇを得た。B- (N-formylamino)ethanol 0.23g,
DCCo. 82g of the mixture was stirred at room temperature overnight. Add toluene, filter out DCU, wash with copper sulfate aqueous solution, dry,
Concentrate and apply silica gel column chromatography to obtain 2-1-(
N-formylamino)ethoxycarbonylmethyl-3.
5-dimethoxycarbonyl-6-methyl-,4-(3”
0.64 g of -ditrophenyl)-1,4-dihydropyridine (compound of Example 1 in the table) was obtained.
実施例２〜２９ 実施例１に倣って表中全ての化合物を得た。Examples 2-29 All compounds in the table were obtained according to Example 1.
本発明化合物の例示及びその物の生理活性を表１）に示
す。Examples of the compounds of the present invention and their physiological activities are shown in Table 1).
Claims (1)
素数１から５の直鎖若しくは分岐鎖の飽和又は不飽和ア
ルキルオキシ基であって、該基はハロゲン、水酸基、ア
リール基、ヘテロ飽和又は不飽和環化合物で置換されて
もよい。又、Ｒ＾２はアラルキルチオ基、若しくは ▲数式、化学式、表等があります▼ （Ｂは炭素数２から５の分岐していてもよいアルキレン
基を、Ｒ＾６、Ｒ＾７は同一又は異なりて水素、アルキ
ル基、置換基を有していてもよいアラルキル基、アシル
基、置換基を有していてもよいアロイル基であるか又は
一方がＢと共に環を形成していてもよい。又、Ｒ＾６、
Ｒ＾７はＮと共にイミド環を成してもよい。）Ｒ＾３、
Ｒ＾５は同一又は異なりて低級アルキル基を示す。） で示される１，４−ジヒドロピリジン化合物及びその塩
。[Claims] Formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, A is a phenyl group having a substituent, R^2 is a linear or branched saturated or An unsaturated alkyloxy group, which may be substituted with a halogen, hydroxyl group, aryl group, heterosaturated or unsaturated ring compound.Also, R^2 is an aralkylthio group, or ▲a mathematical formula, a chemical formula, a table etc. ▼ (B is an optionally branched alkylene group having 2 to 5 carbon atoms, and R^6 and R^7 are the same or different aralkyl which may have hydrogen, an alkyl group, or a substituent. group, an acyl group, an aroyl group which may have a substituent, or one of which may form a ring with B.Also, R^6,
R^7 may form an imide ring together with N. )R^3,
R^5 are the same or different and represent a lower alkyl group. ) A 1,4-dihydropyridine compound and a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28844389A JPH03151362A (en) | 1989-11-06 | 1989-11-06 | 1,4-dihydropyridine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28844389A JPH03151362A (en) | 1989-11-06 | 1989-11-06 | 1,4-dihydropyridine compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03151362A true JPH03151362A (en) | 1991-06-27 |
Family
ID=17730276
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28844389A Pending JPH03151362A (en) | 1989-11-06 | 1989-11-06 | 1,4-dihydropyridine compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03151362A (en) |
-
1989
- 1989-11-06 JP JP28844389A patent/JPH03151362A/en active Pending
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