JPS6126539B2 - - Google Patents

Info

Publication number
JPS6126539B2
JPS6126539B2 JP51041443A JP4144376A JPS6126539B2 JP S6126539 B2 JPS6126539 B2 JP S6126539B2 JP 51041443 A JP51041443 A JP 51041443A JP 4144376 A JP4144376 A JP 4144376A JP S6126539 B2 JPS6126539 B2 JP S6126539B2
Authority
JP
Japan
Prior art keywords
butyl
melting point
pyridine
ditert
group
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
Application number
JP51041443A
Other languages
English (en)
Other versions
JPS52125170A (en
Inventor
Takahiro Kobayakawa
Yoshiaki Tsuda
Hiroshi Yasuda
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Welfide Corp
Original Assignee
Welfide Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Welfide Corp filed Critical Welfide Corp
Priority to JP4144376A priority Critical patent/JPS52125170A/ja
Priority to FR7709451A priority patent/FR2348201A1/fr
Priority to GB14443/77A priority patent/GB1557622A/en
Priority to SE7704197A priority patent/SE7704197L/xx
Priority to DE19772716125 priority patent/DE2716125A1/de
Publication of JPS52125170A publication Critical patent/JPS52125170A/ja
Publication of JPS6126539B2 publication Critical patent/JPS6126539B2/ja
Granted legal-status Critical Current

Links

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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
    • 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/68—One oxygen atom attached in position 4
    • 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • 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
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals

Description

【発明の詳細な説明】
本発明は、一般式 で示される新規なピリジン誘導体に関する。 上記式中、各記号はそれぞれ次を意味する。 Ｙ＝−Ｏ−、−Ｓ−、−Ｎ（R4）− R1、R2＝水素原子、水酸基、低級アルキル基
（メチル、エチルなど） R3＝水素原子、ヒドロキシメチル基または次の
基： R4＝水素原子、低級アルキル基（メチル、エチ
ルなど）、アラルキル基（ベンジル、メトキシ
ベンジル、フエネチルなど） ｎ＝０〜２ ｍ＝０、１ 一般式（）の化合物は、一般式 で示される化合物と、一般式 で示される化合物とを反応させることにより製造
される。ここで、Q1、Q2の一方はハロゲン
（Cl、Brなど）または反応性の基（メチルスルホ
ニルオキシ、ｐ−トリルスルホニルオキシな
ど）、他方は−Ｙ−Ｍ〔Ｙは前記と同義であり、
Ｍは水素原子またはアルカリ金属を示す。〕を示
し、他の記号は前記と同義である。 反応は通常溶媒中で行われる。溶媒としては、
反応に支障のない限りたいていの有機溶媒が用い
られるが、好ましくはベンゼン、ヘキサン、アセ
トン、ジメチルホルムアミドなどがあげられる。
本反応はたとえば炭酸カリウム、炭酸ナトリウ
ム、ナトリウムメチラート、ナトリウムエチラー
ト、ナトリウムハイドライド、トリエチルアミン
などの塩基を添加することにより反応を一層有利
に進行させることができる。塩基の添加量は化合
物（）、（）に対して当量モルか２〜３当量モ
ルを用いるのが好ましい。温度、時間、その他の
条件は用いられる原料、溶媒、塩基などにより適
宜決定される。通常反応は０゜から溶媒の沸点で
１〜数十時間加熱することにより進行する。 このようにして得られるピリジン誘導体（）
は公知の分離手段、濃縮、減圧濃縮、蒸留、減圧
蒸留、分留、溶媒抽出、晶出、再結晶、クロマト
グラフイーなどにより単離精製することができ
る。 本発明方法で得られるピリジン誘導体（）は
遊離の塩基、塩の形で用いれらる。 かくして得られるピリジン誘導体（）は抗動
脈硬化作用、抗脂血作用、能循環改善作用あるい
は抗血栓作用を有し、虚血性循環器疾患、および
老人病などの予防または治療剤として有用であ
る。以下本発明にかかわる化合物が有用であるこ
とを実験方法とともに示す。 (1) 実験的動脈硬化防止作用 エクスペリメンタル・アテロスクリロウシス
（Experimental Atherosclerosis）49ページ
（1965年、エルセビル・パブリツシング・カン
パニー発行）に記載のコンスタンチナイデスの
方法を改変してなつた。すなわち、雄性スプラ
グドーリー系ラツトヘビタミンD2を１日40万
単位／Kg連続５日間経口投与することにより惹
起された大動脈の硬化度を０〜４点に肉眼的に
判定しその平均値を求め試験化合物の改善率を
求めた。結果を表にまとめた。 (2) 抗脂血作用 (i) トライトン高脂血症への作用 雄性ddマウスの腹腔内への試験化合物を
与投後、ただちにトライトンWR−1339を
300mg/Kg静脈内へ投与し18時間後に採血して
血清コレステロール値をオートアナライザー
を使用して測定した。得られた測定値は同様
な処置を受けたプラセボ対照群と比較し、低
下率で表に示した。 (ii) 正常ラツト脂質への作用 雄性ウイスターラツトへ試験化合物を経口
投与し、20時間後、さらに投与を行ない、最
終投与４時間後に屠殺採血しコレステロール
とトリグリセライドの測定をオートアナライ
ザーを使用して測定した。得られた結果は対
照群と比較し、低下率で表に示した。 (3) 脳血流増加作用 無麻酔家兎を人工呼吸下ガラミン不動化し、
脳幹網様体へヒートクリアランス測定用針状電
極を刺入し、ポリグラフを用いて記録した。被
検化合物は静脈内へ投与し、脳血流増加作用は
ヒートクリアランス量との相関性から算出し
た。即ち、最高ヒートクリアランス増加値（Δ
μＶ）と作用持続時間（sec）を乗じ、その平
方根を脳血流増加指数（√×）とし
て、同時に求めたパパベリン塩酸塩のそれと対
比し表に示した。
【表】
【表】
【表】 実施例 １ 乾燥ベンゼン50ml中に、水素化ナトリウム（50
％油性）２ｇを加え、撹拌下に３−ヒドロオキシ
メチルピリジン4.4ｇを溶かしたベンゼン溶液を
10分間で滴下する。滴下後70〜80℃にて１時間撹
拌した後冷却し氷冷下に、３・５−ジ第三級ブチ
ル−４−ヒドロキシベンジルプロマイド10ｇを溶
かしたベンゼン溶液を滴下する。滴下後１時間還
流した後、水を加え、分離した有機層を水洗した
後、硫酸マグネシウムで乾燥し、濃縮して得られ
る油状物質にヘキサンを加えると晶出する。この
結晶をろ取後含水エタノールより再結晶すると、
融点108〜109℃の３−（３・５−ジ第三ブチル−
４−ヒドロキシベンジルオキシメチル）ピリジン
を得る。 実施例 ２ アセトン150ml中に３・５−ジ第三ブチル−４
−ヒドロキシベンジルブロマイド10ｇと２−メル
カプトピリジン4.5ｇを加え室温下で３時間撹拌
する。アセトンを留去したのち、生ずる油状物質
をヘキサンで洗浄後、含水エタノールを加えると
晶出する。結晶をろ取後エタノールより再結晶す
ると、融点100〜101℃の２−（３・５−ジ第三ブ
チル−４−ヒドロキシベンジルチオ）ピリジンを
得る。 実施例 ３ Ｎ−メチル−２−（２−ピリジル）エチルアミ
ン5.0ｇを無水アセトン50mlに溶解させ、無水炭
酸カリウム6.0ｇを加え、室温下に、３・５−ジ
第三ブチル−４−ヒドロキシベンジルブロマイド
10ｇを含むアセトン溶液を滴加し、同温下で30分
間撹拌する。反応後、反応液を濃縮したのち、水
を加え、酢酸エチルで抽出し、水洗後、無水硫酸
マグネシウムで酢酸エチル層を乾燥、過、この
液より溶媒を留去すると結晶が析出する。この
結晶をイソプロピルアルコールより再結すると、
無色砂状晶として、融点93〜94℃のＮ−（３・５
−ジ第三ブチル−４−ヒドロキシベンジル）−Ｎ
−メチル−２−（２−ピリジル）エチルアミンが
得られる。この結晶3.4ｇをエタノール塩酸で処
理し、得られた結晶をイソプロピルアルコールよ
り再結晶すると、無色砂状晶として融点179〜181
℃のＮ−（３・５−ジ第三ブチル−４−ヒドロキ
シベンジル）−Ｎ−メチル−２−（２−ピリジル）
エチルアミン・２塩酸塩が得られる。 以下同様にして、次の化合物が製造される。 (4) ２−〔２−（３・５−ジ第三ブチル−４−ヒド
ロキシベンジルオキシ）エチル〕ピリジン、融
点85〜86℃ (5) ４−（３・５−ジ第三ブチル−４−ヒドロキ
シベンジルオキシ）ピリジン、融点216〜218℃
（分解） (6) ３−（３・５−ジ第三ブチル−４−ヒドロキ
シベンジルアミノメチル）ピリジン・２塩酸
塩、融点236〜238℃（分解） (7) Ｎ−（４−メトキシベンジル）−２−（３・５
−ジ第三ブチル−４−ヒドロキシベンジルアミ
ノ）ピリジン・塩酸塩、融点103〜104℃ (8) ３−（３・５−ジ第三ブチル−４−ヒドロキ
シベンジルアミノ）ピリジン・塩酸塩、融点
207〜208℃ (9) ２・６−ビス（３・５−ジ第三ブチル−４−
ヒドロキシベンジルオキシメチル）ピリジン、
融点124〜126℃ (10) ３−（３・５−ジ第三ブチル−４−ヒドロキ
シフエニルチオメチル）ピリジン、融点137〜
138℃ (11) ３−（３・５−ジ第三ブチル−４−ヒドロキ
シフエノキシメチル）ピリジン、融点128〜130
℃ (12) ２−（３・５−ジ第三ブチル−４−ヒドロキ
シアニリノメチル）ピリジン、融点123〜125℃ (13) ２−（３・５−ジ第三ブチル−４−ヒドロ
キシベンジルオキシ）ピリジン、融点181〜182
℃ (14) ３−（３・５−ジ第三ブチル−４−ヒドロ
キシベンジルオキシ）ピリジン、融点200〜201
℃ (15) ２−（３・５−ジ第三ブチル−４−ヒドロ
キシベンジルオキシメチル）−６−メチルピリ
ジン、融点80〜82℃ (16) ２−（３・５−ジ第三ブチル−４−ヒドロ
キシベンジルオキシメチル）ピリジン、融点
137〜138℃ (17) ２−（３・５−ジ第三ブチル−４−ヒドロ
キシベンジルオキシメチル）６−ヒドロキシメ
チルピリジン、融点106〜108℃ (18) ４−（３・５−ジ第三ブチル−４−ヒドロ
キシアニリノメチル）−３−ヒドロキシ−５−
ヒドロキシメチル−２−メチルピリジン・塩酸
塩、融点237〜238℃ かくして得られる一般式（）の化合物または
その塩は、それ自体あるいは適宜の薬理的に許容
される結合剤（シロツプ、アラビアゴム、ゼラチ
ン、ソルビツト、トラガント、ポリビニルピロリ
ドンなど）、賦形剤（乳糖、砂糖、コーンスター
チ、リン酸カルシウム、ソルビツト、グリシンな
ど）、潤滑剤（ステアリン酸マグネシウム、タル
ク、ポリエチレングリコール、シリカなど）、崩
壊剤（馬鈴薯殿粉など）または湿潤剤（ラウリル
硫酸ナトリウムなど）と混合し、粉末、顆粒、錠
剤またはカプセル剤などの形態で経口的に投与す
ることが望ましい。成人を治療する場合の１日投
与量は100〜2000mg程度で年令、体重、症状など
により投与量が増減されることはいうまでもな
い。

Claims (1)

  1. 【特許請求の範囲】 １ 一般式 で示されるピリジン誘導体。 〔式中 Ｙ＝−Ｏ−、−Ｓ−、−Ｎ（R4）− R1、R2＝水素原子、水酸基、低級アルキル基 R3＝水素原子、ヒドロキシメチル基、または次
    の基： R4＝水素原子、低級アルキル基、アラルキル基 ｎ＝０〜２ ｍ＝０、１ を示す。〕
JP4144376A 1976-04-12 1976-04-12 Pyridine derivatives Granted JPS52125170A (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP4144376A JPS52125170A (en) 1976-04-12 1976-04-12 Pyridine derivatives
FR7709451A FR2348201A1 (fr) 1976-04-12 1977-03-30 Nouveaux medicaments pour le traitement des affections vasculaires ischemiques
GB14443/77A GB1557622A (en) 1976-04-12 1977-04-05 3 5 ditertiary butyl 4 hydroxaphenylpyridine compounds
SE7704197A SE7704197L (sv) 1976-04-12 1977-04-12 Pyridinforeningar
DE19772716125 DE2716125A1 (de) 1976-04-12 1977-04-12 3,5-di-tert.-butyl-4-hydroxyphenylpyridinverbindungen, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zubereitungen

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP4144376A JPS52125170A (en) 1976-04-12 1976-04-12 Pyridine derivatives

Publications (2)

Publication Number Publication Date
JPS52125170A JPS52125170A (en) 1977-10-20
JPS6126539B2 true JPS6126539B2 (ja) 1986-06-20

Family

ID=12608501

Family Applications (1)

Application Number Title Priority Date Filing Date
JP4144376A Granted JPS52125170A (en) 1976-04-12 1976-04-12 Pyridine derivatives

Country Status (5)

Country Link
JP (1) JPS52125170A (ja)
DE (1) DE2716125A1 (ja)
FR (1) FR2348201A1 (ja)
GB (1) GB1557622A (ja)
SE (1) SE7704197L (ja)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63302851A (ja) * 1987-06-02 1988-12-09 Nippon Medical Supply Corp 血小板保存用血液バッグ
JPH0620523Y2 (ja) * 1989-12-07 1994-06-01 川澄化学工業株式会社 医療用容器

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4246263A (en) * 1979-10-15 1981-01-20 Pfizer Inc. Antiinflammatory and immunoregulatory pyrimidines, their method of use and pharmaceutical compositions
USRE31624E (en) * 1979-11-26 1984-07-03 Forsyth Dental Infirmary For Children Method of treating inflammation
US4244956A (en) * 1979-11-26 1981-01-13 Forsyth Dental Infirmary For Children Method of treating inflammation
US4563526A (en) * 1980-09-19 1986-01-07 Forsyth Dental Infirmary For Children Substituted 2-(arylmethoxy) phenol compounds for the treatment of inflammation
DE3216843C2 (de) * 1982-05-05 1986-10-23 Ludwig Heumann & Co GmbH, 8500 Nürnberg 3-Thiomethyl-pyridin-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
US4959364A (en) * 1985-02-04 1990-09-25 G. D. Searle & Co. Method of treating inflammation, allergy, asthma and proliferative skin disease using heterocyclic amides
US5157053A (en) * 1985-02-04 1992-10-20 G. D. Searle & Co. Bicycloalky, tricycloalkyl, azabicycloalkyl, and azatricycloalkyl thio amides used to treat inflammation, allergy, asthma and skin disorders
US5244899A (en) * 1985-02-04 1993-09-14 G. D. Searle And Co. Azabicycloalkyl and azatricycloalkyl amides used to treat inflammation, allergy, asthma and skin disorders
US5071876A (en) * 1985-02-04 1991-12-10 G. D. Searle & Co. Novel disubstituted 4-hydroxyphenylthio anilides
US5225444A (en) * 1985-02-04 1993-07-06 G. D. Searle & Co. Disubstituted 4-hydroxyphenylthio anilides
US5229421A (en) * 1985-05-20 1993-07-20 G. D. Searle & Co. Methods and compositions for inhibiting lipoxygenase
EP0339688B1 (en) * 1985-05-20 1993-03-10 G.D. Searle & Co. Hydroxyphenylthioalkylketones
US4868183A (en) * 1986-07-21 1989-09-19 Otsuka Pharmaceutical Factory, Inc. N-pyrazinyl substituted P-aminophenols
DE3712752A1 (de) * 1987-04-15 1988-11-03 Hoechst Ag Heterocyclische neophananaloga, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel
US5002967A (en) * 1987-06-05 1991-03-26 G. D. Searle & Co. Phenolic thioethers, sulfoxides, and disulfides as inhibitors of 5-lipoxygenase
US4835189A (en) * 1987-06-05 1989-05-30 G. D. Searle & Co. Phenolic thioalkylamides as inhibitors of 5-lipoxygenase
CA2080249C (en) * 1990-05-31 1996-11-19 Dennis M. Godek Preparation of substituted piperidines
US5281623A (en) * 1990-08-27 1994-01-25 Eli Lilly And Company Method for treating inflammation
US5189038A (en) * 1990-09-07 1993-02-23 G. D. Searle And Co. Method of stimulating superoxide generation
CA2088503A1 (en) * 1990-09-07 1992-03-08 Richard August Mueller Phenolic thioetheramides as 5-lipoxygenase inhibitors
US5082854A (en) * 1990-09-07 1992-01-21 G. D. Searle & Co. Method of stimulating superoxide generation
US5254549A (en) * 1991-12-19 1993-10-19 Merz & Co. Gmbh & Co. New BHT ether compounds and their use as hypolipidemic and antiatherosclerotic drugs
LT3339B (en) 1993-03-05 1995-07-25 Merz & Co Gmbh & Co New bht ether compounds and their use as hypolipidemic and antiatherosclerotic drugs
US5585388A (en) * 1995-04-07 1996-12-17 Sibia Neurosciences, Inc. Substituted pyridines useful as modulators of acetylcholine receptors
US6852878B2 (en) 1998-05-14 2005-02-08 Atherogenics, Inc. Thioketals and thioethers for inhibiting the expression of VCAM-1
EP1695959A1 (en) * 1997-05-14 2006-08-30 Atherogenics, Inc. Compouds and methods for the inhibition of the expression of VCAM-1
AU2006202461B2 (en) * 1997-05-14 2009-12-03 Atherogenics, Inc. Compositions and methods for the inhibition of the expression of VCAM-1
CN1275596C (zh) 1997-05-14 2006-09-20 阿特罗吉尼克斯公司 普罗布考单酯在制备用于治疗心血管疾病和炎性疾病的药物中的应用
US6670398B2 (en) 1997-05-14 2003-12-30 Atherogenics, Inc. Compounds and methods for treating transplant rejection
CN1261803A (zh) 1997-07-01 2000-08-02 埃瑟若詹尼克斯公司 抗氧化剂增强对细胞过度增生性疾病的治疗
US6521658B1 (en) 1999-05-28 2003-02-18 Abbott Laboratories Cell proliferation inhibitors
CO5170498A1 (es) * 1999-05-28 2002-06-27 Abbott Lab Biaril sulfonamidas son utiles como inhibidores de proliferacion celular
US7064139B2 (en) * 2001-10-29 2006-06-20 Uniroyal Chemical Company, Inc. Method for treating retroviral infections
WO2005102323A2 (en) 2004-04-20 2005-11-03 Atherogenics, Inc. Process of preparing esters and ethers of probucol and derivatives thereof
JP2010522762A (ja) 2007-03-26 2010-07-08 サルトリア・フアーマシユーテイカルズ・エル・エル・シー 糖尿病の治療のための方法及びプロブコール誘導体の組成物
CN104045552B (zh) * 2013-03-13 2019-06-11 江苏先声药业有限公司 作为神经保护剂的药用化合物

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1010880A (en) * 1972-08-16 1977-05-24 Gustave K. Kohn 3,5-dialkyl-4-hydroxybenzoic acid esters

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63302851A (ja) * 1987-06-02 1988-12-09 Nippon Medical Supply Corp 血小板保存用血液バッグ
JPH0620523Y2 (ja) * 1989-12-07 1994-06-01 川澄化学工業株式会社 医療用容器

Also Published As

Publication number Publication date
SE7704197L (sv) 1977-10-13
DE2716125A1 (de) 1977-10-27
GB1557622A (en) 1979-12-12
FR2348201A1 (fr) 1977-11-10
JPS52125170A (en) 1977-10-20

Similar Documents

Publication Publication Date Title
JPS6126539B2 (ja)
JPS59501409A (ja) ピリドン化合物
CA2069261A1 (fr) Derives de la pyrimidine, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant
JPH0428269B2 (ja)
EP0148167B1 (fr) Nouveaux dérivés de la quinoléine, leur procédé de préparation et les compositions pharmaceutiques les renfermant
US5053416A (en) Derivatives of 1,2,5,6-tetrahydropyridine substituted by a thiazolyl or oxazolyl radical, their use as medicaments and compositions containing them
JP2824661B2 (ja) アザ環式カルボン酸誘導体及びその調剤並びに使用
HUT71132A (en) Bis-aryl-carbinol derivatives, pharmaceutical compositions containing them and process for producing
JPS61130280A (ja) ピペリジン誘導体
JPS63295566A (ja) キノキサリノン誘導体
JPS6160648A (ja) ２−（３，５−ジアルキル−４−ヒドロキシフエニル）インド−ル誘導体
JP2852536B2 (ja) イミダゾール抗不整脈剤
JPH0578554B2 (ja)
JPH07252260A (ja) 新規チエノチアジン誘導体、その製造方法及びその使用方法
JPH05502235A (ja) イミダゾール類
JP2009051731A (ja) 新規アスコクロリン誘導体化合物及びそれを含有する医薬組成物
JP2535533B2 (ja) ベンゾジオキソ−ル誘導体
JP2967989B2 (ja) テトラヒドロピリジン誘導体及びその製法
JPH06135943A (ja) 新規なウラシル誘導体及びそれを有効成分とするアレルギー疾患治療薬
CH616425A5 (ja)
JPH07100695B2 (ja) 新規なピペリジン化合物およびその製薬組成物
JPS60226877A (ja) ピペリジン誘導体
JPH01211580A (ja) 置換イミダゾール誘導体
KR830002276B1 (ko) 4-(2'-피리딜 아미노) 페닐 아세트산 유도체의 제조방법
WO1996005202A1 (fr) Derive de l'imidazoquinoleine