JPS6043352B2 - Novel compounds, their production methods and pharmaceutical compositions containing them - Google Patents
Novel compounds, their production methods and pharmaceutical compositions containing themInfo
- Publication number
- JPS6043352B2 JPS6043352B2 JP51031891A JP3189176A JPS6043352B2 JP S6043352 B2 JPS6043352 B2 JP S6043352B2 JP 51031891 A JP51031891 A JP 51031891A JP 3189176 A JP3189176 A JP 3189176A JP S6043352 B2 JPS6043352 B2 JP S6043352B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- group
- hydrogen atom
- tables
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
-
- 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
Description
【発明の詳細な説明】
本発明は薬学的に活性な化合物およびその製法ならびに
その化合物を含む製成物に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to pharmaceutically active compounds and processes for their preparation, as well as compositions containing the compounds.
薬剤を投与する際、通常起こる問題として、いわゆる′
６リパウンド効果（ＲｅｂＯｕｎｄＥｆｆｅｃｔ）′１
のため時々所望の薬理的作用が期待したほど有効に生じ
なくなる傾向がある。本発明者らはある種の酸性薬剤の
場合、ある種のエステル形で投与するとこの問題が少な
くなることを発見した。さらに、これらエステルの中に
はその使用によつて投与後の有効期間を延長できるもの
もある。従つて、本発明は式（１）
（式中、Ｒは水素原子またはメチル基であり、ｎは１〜
３の数である。When administering drugs, a common problem is the so-called
6RebOundEffect'1
Therefore, the desired pharmacological effect sometimes tends to occur less effectively than expected. The inventors have discovered that for certain acidic drugs, this problem is lessened when administered in certain ester forms. Furthermore, the use of some of these esters can extend the shelf life after administration. Therefore, the present invention relates to formula (1) (wherein R is a hydrogen atom or a methyl group, and n is 1 to
The number is 3.
）で表わされる化合物を提供するものである。式（１）
の化合物において最適のＲは水素原子である。) is provided. Formula (1)
The optimum R in the compound is a hydrogen atom.
式（１）の化合物において最適のｎは１または２である
。式（１）の化合物において特に好ましい一ＣＨＲ−（
ＣＨ２）ｎ一残基は−ＣＨ２−ＣＨ２一基である。Optimal n in the compound of formula (1) is 1 or 2. Particularly preferred in the compound of formula (1) is CHR-(
One CH2)n residue is one -CH2-CH2 group.
本発明の好ましい化合物は血清脂質
（Ｓｅｒｕｍｌｌｐｉｄｓ）に対して特に受容できる薬
理作用を有する１−（テオフイリニルー７−メチレンカ
ルボニルオキシ）−２−（ニコチノイルオキシ）エタン
である。A preferred compound of the invention is 1-(theophyrinyl-7-methylenecarbonyloxy)-2-(nicotinoyloxy)ethane, which has a particularly acceptable pharmacological effect on serum lipids.
ここで血清脂質に対する薬理作用とはトリグリセリド及
びコレステロールのような血清脂質の水準を減少させる
作用効果を意味する。本発明はまた、
（ａ）式（■）
（式中、Ｒおよびｎは前記式（１）に関して定義した通
りであり、Ｘはヒドロキシル基または容易に置換可能な
基である）で表わされる化合物と、式（■）の化合物ま
たはそのアシル化誘導体とを反応させること；あるいは
（ｂ）式（■）
（式中、ｎは前記式（１）に関して定義した通りであり
、Ｘはヒドロキシル基または容易に置換可能な基である
）で表わされる化合物とテオフイリニル酢酸またはその
アシル化誘導体とを反応させることから成る、式（１）
の化合物を製造する方法をも提供するものである。Here, the pharmacological effect on serum lipids refers to the effect of reducing the level of serum lipids such as triglycerides and cholesterol. The present invention also provides (a) a compound represented by formula (■) (wherein R and n are as defined with respect to formula (1) above, and X is a hydroxyl group or an easily substitutable group); and (b) a compound of formula (■) or an acylated derivative thereof; or (b) formula (■), where n is as defined in relation to formula (1) above, and X is a hydroxyl group or Formula (1), which consists of reacting a compound represented by (which is an easily substitutable group) with theophyrinyl acetic acid or an acylated derivative thereof.
A method for producing the compound is also provided.
Ｘがヒドロキシル基である式（■）または（■）の化合
物と反応させるための適当な式（■）の化合物またま適
当なテオフイリニル酢酸の誘導体には、ジシクロヘキシ
ルカルボジイミドのような脱水剤の存在下における遊離
酸あるいは酸塩物のような酸ハロゲン化物または酸無水
物または混合無水物などの遊離酸の誘導体が含まれる。A suitable compound of formula (■) or a suitable derivative of theophylinyl acetic acid for reaction with a compound of formula (■) or (■) in which X is a hydroxyl group may be reacted with a compound of formula (■) or (■) in which X is a hydroxyl group in the presence of a dehydrating agent such as dicyclohexylcarbodiimide. Derivatives of free acids such as acid halides or acid anhydrides or mixed anhydrides, such as free acids or acid salts, are included.
Ｘが塩素、臭素または沃素原子あるいはメタンスルホニ
ルまたはトルエンスルホニルエステルのような活性化エ
ステルなどの置換可能な基である式（■）または（■）
の化合物と反応させるために好ましい式（■）の化合物
の誘導体またはテオフイリニル酢酸の誘導体は例えばナ
トリウム塩のようなアルカリ金属塩または類似の塩のよ
うな塩である。Formula (■) or (■) in which X is a substitutable group such as a chlorine, bromine or iodine atom or an activated ester such as methanesulfonyl or toluenesulfonyl ester
Preferred derivatives of the compound of formula (■) or derivatives of theophyrinyl acetic acid for reaction with the compound are salts such as alkali metal salts such as the sodium salt or similar salts.
上記の反応はエステル製造のために通常用いられる条件
下で行うことができる。The above reaction can be carried out under conditions commonly used for ester production.
かかる反応に用いるのに適した溶媒には、ジメチルホル
ムアミド、ベンゼン、ピリジンなどの不活性有機溶媒が
含まれる。Solvents suitable for use in such reactions include inert organic solvents such as dimethylformamide, benzene, pyridine, and the like.
本発明はまた製薬上許容し得る担体とともに式（１）の
化合物を含む製剤組成物をも提供する。The present invention also provides pharmaceutical compositions comprising a compound of formula (1) together with a pharmaceutically acceptable carrier.
本発明の組成物はヒトの悪性高脂肪症状態（Ａｄｖｅｒ
ｓｅｈｙｐｅｒｌｉｐｅｄｅｍｊｃａｔａｔｅ）の治療
に特に有用である。The composition of the present invention can be used to treat malignant hyperlipidemia (Adver) in humans.
It is particularly useful in the treatment of hyperlipidemia.
かかる治療に際して、本発明の化合物は一般に経口投与
されるが、非経口投与方法を用いることもできる。典型
的な経口投与用製剤（ＦＯｒｍｕｌａｔｉＯｎ）は錠剤
、丸剤、カプセル、におい袋（Ｓａｃｈｅｔｓ）、顆粒
剤、散剤、チユーインガム、懸濁剤、乳剤および液剤で
あり、特に好ましい経口投与用製剤は錠剤およびカプセ
ルである。In such treatments, the compounds of the present invention are generally administered orally, although parenteral methods of administration can also be used. Typical formulations for oral administration are tablets, pills, capsules, sachets, granules, powders, chewing gums, suspensions, emulsions and solutions; particularly preferred formulations for oral administration are tablets and capsules. It is.
本発明の組成物は適宜、通常の希釈剤、結合剤、分散剤
、界面活性剤、潤ノ滑剤、コーティング剤、香味料、着
色料、溶剤、増粘剤、懸濁剤、甘味料あるいはその他の
薬学的に受容できる添加物、例えばゼラチン、乳糖、殿
粉、タルク、ステアリン酸マグネシウム、水素化油、ポ
リグリコールおよびシロツプを含むことが．できる。製
剤が錠剤またはカプセルおよびその類似製剤であ場合、
予め計量された単囲服用量をざ示すが、顆粒剤、散剤、
懸濁剤およびその類似製剤の場合には、予め計量された
単量服用量として与えられることもできるし、あるいは
適当な単位″服用量を取出すことができる多数回服用用
容器中に入れて与えることもできる。注射用組成物は薬
学的に受容できる液体中の水系または非水系溶液、懸濁
剤または乳剤の形にすることができる。The compositions of the present invention may optionally contain conventional diluents, binders, dispersants, surfactants, lubricants, coatings, flavors, colorants, solvents, thickeners, suspending agents, sweeteners or other additives. Pharmaceutically acceptable additives such as gelatin, lactose, starch, talc, magnesium stearate, hydrogenated oils, polyglycols and syrups. can. If the preparation is a tablet or capsule and similar preparations,
We provide pre-measured single sieve doses for granules, powders,
In the case of suspensions and similar preparations, they may be presented as premeasured single doses or in multi-dose containers from which suitable unit" doses can be dispensed. Injectable compositions can be in the form of aqueous or non-aqueous solutions, suspensions, or emulsions in pharmaceutically acceptable liquids.
本発明の組成物の好ましい投与剤形は経口投与用として
予め計量された服用量を含む通常の錠剤またはカプセル
である。A preferred dosage form for the compositions of the invention is a conventional tablet or capsule containing a pre-metered dose for oral administration.
かかる投与剤は通常、式（１）の化合物を１０〜５００
ｍ９含み、好ましい含有量は２５〜３００ｍ９である。
かかる剤形のものを１日１〜６回服用させる。体重７０
ｋ９の成人の最大１日分服用量は通常１５００ｍｇ以下
であり、１０００ｍ９以下の１日分服用量が一般に好ま
しい。通常、体重７０ｋ９の成人に対する１日分服用量
は２５ｍ９以下であり、普通５０ｍ９以上である。本発
明の成物は通常の混合、ブレンテイング、製錠などの方
法で製造することができる。Such dosages usually contain 10 to 500 doses of the compound of formula (1).
The preferred content is 25 to 300 m9.
This dosage form is administered 1 to 6 times a day. Weight 70
The maximum daily dose for adults with K9 is usually less than 1500 mg, and daily doses less than 1000 m9 are generally preferred. Normally, the daily dose for an adult weighing 70k9 is less than 25m9, and usually more than 50m9. The composition of the present invention can be manufactured by conventional mixing, blending, tabletting, etc. methods.
以下に本発明の実施例を示す。Examples of the present invention are shown below.
実施例１
１−（テオフイリニルー７−メチレンカルボニルオキシ
）−２−（ニコチノイルオキシ）エタンテオフイリニル
ー７一酢酸β−ヒドロキシエチルエステル（５６．５ｆ
）とピリジン（３２ｍ１）とクロロホルム（５００ｍ１
）とを一緒にして１時間攪拌し、これに塩化二コチノイ
ル塩酸塩（４２ダ）をクロロホルム（２００ｍｔ）とピ
リジン（３２ｍｔ）との混合物に溶解したものを加えた
。Example 1 1-(Theophylinyl-7-methylenecarbonyloxy)-2-(nicotinoyloxy)ethane Theophylinyl-7-monoacetic acid β-hydroxyethyl ester (56.5f
), pyridine (32ml) and chloroform (500ml)
) and stirred for 1 hour, and to this was added dicotinoyl chloride hydrochloride (42 da) dissolved in a mixture of chloroform (200 mt) and pyridine (32 mt).
この反応混合物を室温で２肴間攪拌した後、水（５００
ｍ１）で希釈し、クロロホルム相を分離し、乾燥、蒸発
させて結晶性物質（７７．１ｙ）を得た。この結晶性物
質の試料を水から再結晶させて所望の化合物（Ｍ．Ｐ．
ｌ８ｒＣ）を得た。かくして得られた表題化合物のラッ
トにおける経口ＬＤ５Ｏは１ｆＩｋ９より大きい。This reaction mixture was stirred at room temperature for two minutes, and then water (500
The chloroform phase was separated, dried and evaporated to give a crystalline material (77.1y). A sample of this crystalline material was recrystallized from water to yield the desired compound (M.P.
l8rC) was obtained. The oral LD5O of the title compound thus obtained in rats is greater than 1fIk9.
１詩間断食ラット（Ｓｔａｎｕｅｄｒａｔｓ）に表題化
合物３００ｍ９１ｋｇを経口投与した場合、投与後１時
間で血清トリグリセリドおよびコレステロールがおのお
の３０％低下した。When 300 m91 kg of the title compound was orally administered to Stanuedrats, serum triglycerides and cholesterol were each reduced by 30% one hour after administration.
これらのテストで使用されたラットは成熟した雄のウイ
スター種のラット（Ｗｉｓｔａｒｒａｔｓ）である。上
と同様な方法を用いて１−（テオフイリニルー７−メチ
レンカルボニルオキシ）−４−（ニコチノイルオキシ）
ブタン（Ｍ．ｐ．ｌ４８〜１５０℃を製造することがで
きた。The rats used in these tests were adult male Wistar rats. 1-(theophyrinyl-7-methylenecarbonyloxy)-4-(nicotinoyloxy) using a method similar to above.
It was possible to produce butane (M.p.l 48-150°C).
実施例２
２−（テオフイリニルー７−メチレンカルボニルオキシ
）−３−（ニコチノイルオキシ）プロノ寸ンニコチン酸
２−ヒドロキシプロピルエステル（１５．０３ｆ）をピ
リジン（１００ｍｔ）に溶解し、これにテオフイリニル
ー７−メチレンカルボニルクロリド（２１．３３ｙ）を
クロロホルム（２５０ｍＬ）に溶解した溶液を１転間に
わたつて滴加した。Example 2 2-(Theophylinyl-7-methylenecarbonyloxy)-3-(nicotinoyloxy)pronotin nicotinic acid 2-hydroxypropyl ester (15.03f) was dissolved in pyridine (100 mt), and theophylinyl-7-methylene was dissolved in this. A solution of carbonyl chloride (21.33y) in chloroform (250 mL) was added dropwise over one inversion.
Claims (1)
は水素原子またはメチル基であり、そしてｎは１〜３の
数である）で表わされる化合物。 ２ ｎが１である特許請求の範囲第１項記載の化合物。 ３ Ｒが水素原子である特許請求の範囲第１項記載の化
合物。４ 基−ＣＨＲ−（ＣＨ＿２）＿ｎ−が−ＣＨ＿
２−ＣＨ＿２−基である特許請求の範囲第１項記載の化
合物。 ５ 化合物が１−（テオフイリニル−７−メチレンカル
ボニルオキシ）−２−（ニコチノイルオキシ）エタンで
ある特許請求の範囲第１項記載の化合物。６ 式（ I
） ▲数式、化学式、表等があります▼（ I ）（式中、Ｒ
は水素原子またはメチル基であり、そしてｎは１〜３の
数である）で表わされる化合物を製造する方法において
、式（III） ▲数式、化学式、表等があります▼（III）（式中、Ｒ
およびｎは前記式（ I ）に関して定義した通りであり
、Ｘはヒドロキシル基または容易に置換可能な基である
）で表わされる化合物と式（IV）▲数式、化学式、表等
があります▼（IV）の化合物またはそのアシル化誘導体
とを反応させることを特徴とする前記式（ I ）の化合
物を製造する方法。 ７ 式（ I ） ▲数式、化学式、表等があります▼（ I ）（式中、Ｒ
は水素原子またはメチル基であり、そしてｎは１〜３の
数である）で表わされる化合物を製造する方法において
、式（Ｖ） ▲数式、化学式、表等があります▼（Ｖ）（式中、Ｒお
よびｎは前記式（ I ）に関して定義した通りであり、
Ｘはヒドロキシル基または容易に置換可能な基である）
で表わされる化合物とテオフィリニル酢酸またはそのア
シル化誘導体とを反応させることを特徴とする前記式（
I ）の化合物を製造する方法。 ８ 製薬上許容し得る担体と式（ I ） ▲数式、化学式、表等があります▼ （式中、Ｒは水素原子またはメチル基であり、そしてｎ
は１〜３の数である）で表わされれる化合物とからなる
悪性高脂肪症治療用組成物。 ９ 製薬上許容し得る担体と１−（テオフイリニル−７
−メチレンカルボニルオキシ）−２−（ニコチノイルオ
キシ）エタンとからなる経口投与可能な特許請求の範囲
第８項記載の組成物。[Claims] 1 Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R
is a hydrogen atom or a methyl group, and n is a number from 1 to 3). 2. The compound according to claim 1, wherein n is 1. 3. The compound according to claim 1, wherein R is a hydrogen atom. 4 group -CHR-(CH_2)_n- is -CH_
The compound according to claim 1, which is a 2-CH_2- group. 5. The compound according to claim 1, wherein the compound is 1-(theophyrinyl-7-methylenecarbonyloxy)-2-(nicotinoyloxy)ethane. 6 Formula ( I
) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R
is a hydrogen atom or a methyl group, and n is a number from 1 to 3. ,R
and n are as defined in relation to formula (I) above, and X is a hydroxyl group or an easily substitutable group) and formula (IV) ▲ Numerical formula, chemical formula, table, etc. ▼ (IV ) or an acylated derivative thereof. 7 Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R
is a hydrogen atom or a methyl group, and n is a number from 1 to 3. , R and n are as defined for formula (I) above,
X is a hydroxyl group or an easily substitutable group)
The above-mentioned formula (which is characterized by reacting a compound represented by
Method for producing the compound of I). 8. Pharmaceutically acceptable carrier and formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R is a hydrogen atom or a methyl group, and n
is a number from 1 to 3). 9 A pharmaceutically acceptable carrier and 1-(theophyrinyl-7)
-methylenecarbonyloxy)-2-(nicotinoyloxy)ethane. The orally administrable composition according to claim 8.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752512886 DE2512886A1 (en) | 1975-03-24 | 1975-03-24 | NEW ESTERS OF THEOPHYLLINYL-7-ACETIC ACID, PROCESS FOR THEIR PREPARATION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS |
| DE2512886.3 | 1975-03-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS51118794A JPS51118794A (en) | 1976-10-18 |
| JPS6043352B2 true JPS6043352B2 (en) | 1985-09-27 |
Family
ID=5942253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51031891A Expired JPS6043352B2 (en) | 1975-03-24 | 1976-03-23 | Novel compounds, their production methods and pharmaceutical compositions containing them |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS6043352B2 (en) |
| AR (2) | AR211336A1 (en) |
| AT (1) | AT344191B (en) |
| BE (1) | BE839890A (en) |
| CA (1) | CA1051890A (en) |
| CH (1) | CH605950A5 (en) |
| DK (1) | DK140843B (en) |
| ES (2) | ES446321A1 (en) |
| FI (1) | FI760755A (en) |
| FR (1) | FR2305184A1 (en) |
| GB (1) | GB1496298A (en) |
| HU (1) | HU174879B (en) |
| IE (1) | IE42788B1 (en) |
| NL (1) | NL7603103A (en) |
| SE (2) | SE419864B (en) |
| ZA (1) | ZA761801B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2714883A1 (en) * | 1977-04-02 | 1978-10-12 | Basf Ag | NON-GLYCOSIDIC THEOPHYLLIN SUGAR DERIVATIVES |
-
1976
- 1976-03-18 GB GB10871/76A patent/GB1496298A/en not_active Expired
- 1976-03-19 FR FR7608048A patent/FR2305184A1/en active Granted
- 1976-03-22 AT AT209376A patent/AT344191B/en not_active IP Right Cessation
- 1976-03-22 IE IE601/76A patent/IE42788B1/en unknown
- 1976-03-22 FI FI760755A patent/FI760755A/fi not_active Application Discontinuation
- 1976-03-22 BE BE165447A patent/BE839890A/en not_active IP Right Cessation
- 1976-03-23 DK DK128076AA patent/DK140843B/en not_active IP Right Cessation
- 1976-03-23 JP JP51031891A patent/JPS6043352B2/en not_active Expired
- 1976-03-23 SE SE7603564A patent/SE419864B/en unknown
- 1976-03-23 CA CA248,568A patent/CA1051890A/en not_active Expired
- 1976-03-24 ES ES446321A patent/ES446321A1/en not_active Expired
- 1976-03-24 HU HU76WU24A patent/HU174879B/en unknown
- 1976-03-24 ZA ZA761801A patent/ZA761801B/en unknown
- 1976-03-24 CH CH365876A patent/CH605950A5/xx not_active IP Right Cessation
- 1976-03-24 NL NL7603103A patent/NL7603103A/en not_active Application Discontinuation
- 1976-03-26 AR AR262675A patent/AR211336A1/en active
- 1976-11-08 AR AR265378A patent/AR217246A1/en active
-
1977
- 1977-06-14 ES ES459777A patent/ES459777A1/en not_active Expired
-
1979
- 1979-03-19 SE SE7902463A patent/SE7902463L/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE7603564L (en) | 1976-09-25 |
| DK140843C (en) | 1980-04-28 |
| JPS51118794A (en) | 1976-10-18 |
| ATA209376A (en) | 1977-11-15 |
| FR2305184B1 (en) | 1979-09-21 |
| CH605950A5 (en) | 1978-10-13 |
| ZA761801B (en) | 1977-03-30 |
| AT344191B (en) | 1978-07-10 |
| IE42788L (en) | 1976-09-24 |
| AR211336A1 (en) | 1977-11-30 |
| NL7603103A (en) | 1976-09-28 |
| ES459777A1 (en) | 1978-04-01 |
| IE42788B1 (en) | 1980-10-22 |
| DK140843B (en) | 1979-11-26 |
| HU174879B (en) | 1980-03-28 |
| BE839890A (en) | 1976-09-22 |
| FR2305184A1 (en) | 1976-10-22 |
| SE7902463L (en) | 1979-03-19 |
| CA1051890A (en) | 1979-04-03 |
| SE419864B (en) | 1981-08-31 |
| ES446321A1 (en) | 1977-10-01 |
| DK128076A (en) | 1976-09-25 |
| FI760755A (en) | 1976-09-25 |
| AR217246A1 (en) | 1980-03-14 |
| GB1496298A (en) | 1977-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH01230516A (en) | Drug containing 3-aminopropoxyaryl derivative | |
| JPH0222271A (en) | Conjugated gamma-oxybutenolide compound and antitumor agent containing said compound as active component | |
| WO2000023437A1 (en) | Nitrogenous fused heterocycle compounds, process for the preparation thereof and agents containing the same | |
| EP0508334B1 (en) | Novel aminophenol derivatives and pharmaceutical compositions thereof | |
| HU187922B (en) | Process for preparing 3-/n,n-dimethyl-carbamoyl/-pyrazolo/1,5-a/-pyridine | |
| KR20040051485A (en) | Optically active bicyclol, preparation thereof and composition containing the same and the use | |
| JPS6043352B2 (en) | Novel compounds, their production methods and pharmaceutical compositions containing them | |
| US4029666A (en) | Benzenesulfonyl-ureas and process for preparing them | |
| US3870792A (en) | Certain dihydrophthalizines for treating hemorrhage and thrombosis | |
| US4006183A (en) | Substituted α-methylsulfinyl-o-toluidines | |
| US4464379A (en) | Indol acetic acid derivatives and anti-inflamatory and related uses thereof | |
| US4060617A (en) | Esters of the ophyllinylacetic acid | |
| CZ321095A3 (en) | Heterocyclic compounds | |
| JPS63310825A (en) | Medicinally useful n-imidazolyl derivative of bicyclic compound | |
| JPH01104064A (en) | Basically substituted benzofurancarboxylic acid amide, manufacture and medicine | |
| EP0047358B1 (en) | Indol acetic derivatives, process for producing the same and pharmaceutical compositions comprising the same | |
| JPS6281365A (en) | Guanidinoethanethiosulfonic acid, production thereof and cholesterol-lowering agent containing said derivative | |
| KR950003499B1 (en) | 1,3,5-trithiane derivatives | |
| US4237132A (en) | Morpholinone derivatives and method of use | |
| US4358441A (en) | Nicotinic derivatives of glucosamine and related pharmaceutical compositions | |
| JPS5844657B2 (en) | 2 3- Polymethylene-5- Sulfamoyl Ansoku Kousan Ruino Goseihou | |
| US3887548A (en) | Pyrazole derivatives | |
| JPS61210092A (en) | Dihydropyridine-5-phosphonic acid diamide derivative | |
| JPH03206038A (en) | Antibacterial agent | |
| JPH0343249B2 (en) |