JPS63230670A - Substituted pyridiylacetic acid derivative - Google Patents
Substituted pyridiylacetic acid derivativeInfo
- Publication number
- JPS63230670A JPS63230670A JP6418687A JP6418687A JPS63230670A JP S63230670 A JPS63230670 A JP S63230670A JP 6418687 A JP6418687 A JP 6418687A JP 6418687 A JP6418687 A JP 6418687A JP S63230670 A JPS63230670 A JP S63230670A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- carbon atoms
- pyridyl
- methyl
- substituted
- 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
- 239000002253 acid Substances 0.000 title claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- BPSNETAIJADFTO-UHFFFAOYSA-N 2-pyridinylacetic acid Chemical class OC(=O)CC1=CC=CC=N1 BPSNETAIJADFTO-UHFFFAOYSA-N 0.000 claims description 8
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 32
- -1 pyridylacetic acid ester Chemical class 0.000 abstract description 27
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 abstract description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 5
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 abstract description 5
- 239000003960 organic solvent Substances 0.000 abstract description 4
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- 231100000053 low toxicity Toxicity 0.000 abstract description 2
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- 229910052744 lithium Inorganic materials 0.000 description 2
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- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- ASUAYTHWZCLXAN-UHFFFAOYSA-N prenol Chemical compound CC(C)=CCO ASUAYTHWZCLXAN-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011251 protective drug Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- CRDAMVZIKSXKFV-UHFFFAOYSA-N trans-Farnesol Natural products CC(C)=CCCC(C)=CCCC(C)=CCO CRDAMVZIKSXKFV-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Pyridine Compounds (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〕
本発明は一般式(I)
〔式中、R1は炭素数1〜5のアルキル基または基
(式中、ηは1〜5の整数を表わす)を示し、R2は水
素原子、炭素数1〜5のアルキル基またはフェニル基を
示し、XIおよびX2は、独立に、水素原子、炭素数1
〜5の低級アルキル基、炭素数1〜5の低級アルコキシ
基または炭素数1〜5のハロゲン置換低級アルコキシ基
のいずれかを示す(但し、Xlおよびx2が共に水素原
子である場合は除く)〕
で表わされる置換ピリジル酢酸誘導体またはその薬理学
上許容される酸付加塩およびそれを有効成分として含む
医薬に関する。Detailed Description of the Invention [Industrial Application Field] The present invention relates to the general formula (I) [wherein R1 is an alkyl group or group having 1 to 5 carbon atoms (in the formula, η is an integer of 1 to 5] ), R2 represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a phenyl group;
~5 lower alkyl group, a lower alkoxy group having 1 to 5 carbon atoms, or a halogen-substituted lower alkoxy group having 1 to 5 carbon atoms (excluding cases where both Xl and x2 are hydrogen atoms)] The present invention relates to a substituted pyridyl acetic acid derivative represented by the above formula or a pharmacologically acceptable acid addition salt thereof, and a pharmaceutical containing the same as an active ingredient.
本発明に係る前記一般式(りを有する置換ピリジル酢酸
誘導体およびその薬理学上許容される酸付加塩は消化性
潰瘍の攻撃因子の抑制効果および防御因子の増強効果を
有し、且つ低毒性であるので消化性潰瘍の治療剤として
有用な新規化合物である。The substituted pyridyl acetic acid derivatives having the general formula (R) and pharmacologically acceptable acid addition salts thereof according to the present invention have the effect of suppressing the aggressive factors and the effect of enhancing the protective factors of peptic ulcers, and have low toxicity. Therefore, it is a new compound useful as a therapeutic agent for peptic ulcers.
消化性潰瘍の病因は攻撃因子と防御因子との不均衡で論
じられているが、組織の抵抗性を増加させる因子はいま
だ不明である。従って“酸のないところに潰瘍はない′
°という言葉は、いまだ格言として生き続けており、消
化性潰瘍の治療目標は、依然として胃酸のコントロール
に向けられているのが現状である。The pathogenesis of peptic ulcer disease has been discussed in terms of an imbalance between offensive and protective factors, but the factors that increase tissue resistance are still unclear. Therefore, “there is no ulcer where there is no acid.”
The word "°" still lives on as a saying, and the current treatment goal for peptic ulcer disease is still aimed at controlling gastric acid.
抗コリン作動薬、例えばアトロビン等の薬剤は胃を無酸
に近い状態にすることができるが、これらも潰瘍の悪化
および再発防止に対してはあまり有効とはいえない。Anticholinergic drugs, such as atrobin, can make the stomach nearly acid-free, but these are also not very effective in preventing ulcer worsening and recurrence.
前記したように、潰瘍が新たに発生するのを防ぐ、すな
わち攻撃因子を抑制する薬物だけでは潰瘍治療に充分な
効果を望めない、従って、現状は攻撃因子の抑制薬と再
発予防のための胃粘膜保護薬が、それぞれ、症状に応じ
て潰瘍治療薬として選ばれている。かかる両方の作用を
有すると云われている化合物も、いくつか提案されてい
るが、これらは実際には攻撃因子の抑制作用が弱く、胃
粘膜保護作用を主とするものであった。As mentioned above, drugs that prevent new ulcers from occurring, that is, drugs that suppress aggressive factors alone cannot be expected to be sufficiently effective in treating ulcers. Mucosal protective drugs are selected as ulcer treatments depending on the symptoms. Several compounds have been proposed that are said to have both of these effects, but in reality, these have only a weak suppressive effect on attacking factors, and their main effect is to protect the gastric mucosa.
前述の如く、攻撃因子の防御及び胃粘膜保護の真作用が
バランスした強力な抗消化性潰瘍薬の開発が強く望まれ
ている。さらに消化性潰瘍剤として出来るだけ毒性及び
副作用が少ないことも重要である。As mentioned above, there is a strong desire to develop a powerful anti-peptic ulcer drug that has a balanced effect of protecting against attacking factors and protecting the gastric mucosa. Furthermore, it is important that the agent has as little toxicity and side effects as possible as a peptic ulcer agent.
従って、本発明者らはこれら活性面、毒性面を主眼とし
た薬剤の開発を企画、諌討した結果、これらの活性がよ
くバランスし、しかも弱毒性の新規な化合物である本発
明の置換ピリジル酢酸誘導体を得ることに成功し、本発
明を完成するに至ったのである。Therefore, the present inventors planned and discussed the development of a drug focusing on these active and toxic aspects, and as a result, the substituted pyridyl of the present invention is a novel compound with well-balanced activities and weak toxicity. They succeeded in obtaining an acetic acid derivative and completed the present invention.
本発明に係る前記一般式(I)で表わされる新規化合物
置換ピリジル酢酸誘導体およびその薬理学上許容される
酸付加塩は胃酸分泌抑制効果と共に胃粘膜保護作用を有
し、且つ弱毒性のため消化性潰瘍の治療に用いることが
できる有用な物質である。The novel compound-substituted pyridyl acetic acid derivative represented by the general formula (I) and its pharmacologically acceptable acid addition salt according to the present invention have a gastric acid secretion suppressing effect and a gastric mucosal protective effect, and are weakly toxic and therefore difficult to digest. It is a useful substance that can be used to treat ulcers.
本発明の前記一般式(I)で表わされる化合物は、例え
ば以下の様にして合成することができる。The compound represented by the general formula (I) of the present invention can be synthesized, for example, as follows.
即ち、一般式(II)
(式中R’ 、X’およびx2は上に定義した通り)で
表わされる置換ピリジル酢酸エステルに、有機溶媒中に
て、塩基の存在下に一78℃〜0℃の温度で二硫化炭素
を作用させる。反応は数分から数十分で完結する0反応
完結後、沃化メチルを加え、数時間撹拌することにより
一般式(I[)(式中、RI、XlおよびX2は上に定
義した通りである)を有する付加体を得ることができる
。That is, a substituted pyridyl acetate represented by general formula (II) (wherein R', Carbon disulfide is applied at a temperature of . The reaction is completed in minutes to tens of minutes. After completion of the reaction, methyl iodide is added and stirred for several hours to obtain the general formula (I[) (where RI, Xl and X2 are as defined above). ) can be obtained.
前記反応に用いることができる溶媒としては、例えばテ
トラヒドロフラン、エーテル、ジメ)・キシエタンまた
はジオキサンなどのエーテル系、例えばベンゼン、トル
エンもしくはキシレンなどの芳香族炭化水素系またはジ
メチルスルホキシドなどが挙げられる。一方、前記反応
に用いられる塩基としては、アルキルリチウム試薬、ナ
トリウムアミド、カリウムアミド、水素化ナトリウム、
水素化カリウム、カリウムt−ブトキシド、ナトリウム
アルコラード、カリウムアルコラード、金属ナトリウム
などを使用するのが好ましい。Examples of solvents that can be used in the reaction include ethers such as tetrahydrofuran, ether, dimethane)xyethane or dioxane, aromatic hydrocarbons such as benzene, toluene or xylene, and dimethyl sulfoxide. On the other hand, the bases used in the reaction include alkyl lithium reagents, sodium amide, potassium amide, sodium hydride,
Preference is given to using potassium hydride, potassium tert-butoxide, sodium alcoholade, potassium alcoholade, metallic sodium, and the like.
前記反応に使用される塩基の量には特に制限はなく、例
えば前記化合物(II)に対し、1〜1.2当量で十分
である。The amount of base used in the reaction is not particularly limited, and for example, 1 to 1.2 equivalents relative to the compound (II) is sufficient.
このようにして得られる一般式(I[[)を有する付加
体は一般に用いられる精製方法、例えばクロマトグラフ
ィー、再結晶または蒸留により精製することができる。The adduct having the general formula (I[[) thus obtained can be purified by commonly used purification methods, such as chromatography, recrystallization or distillation.
次に、前記化合物(IN)に水、水と有機溶媒または有
機溶媒中一般式(IV)
R2−Nl2(IV)
(式中、R2は上に定義した通りである)で表わされる
アンモニアまたはアミン類を10〜30時間反応せしめ
ることにより本発明の化合物を得ることができる。この
反応に用いられる溶娠は反応に関与しないものであれば
特に制限はなく、例えば、水、アルコール系溶媒、塩素
系溶媒、芳香族炭化水素系溶媒、エーテル系溶媒または
酢酸エステル系溶媒を使用するのが好ましい。Next, the compound (IN) is added with water, water and an organic solvent, or ammonia or an amine represented by the general formula (IV) R2-Nl2(IV) (wherein R2 is as defined above). The compound of the present invention can be obtained by reacting these compounds for 10 to 30 hours. The solvent used in this reaction is not particularly limited as long as it does not participate in the reaction; for example, water, alcohol solvents, chlorine solvents, aromatic hydrocarbon solvents, ether solvents, or acetate solvents are used. It is preferable to do so.
反応終了後、所望化合物は、再結晶、カラムクロマトグ
ラフィー等により精製することも出来るし、又薬理学上
許容される酸と処理し、酸付加塩として再結晶又はクロ
マトグラフィーにより精製することもできる。After completion of the reaction, the desired compound can be purified by recrystallization, column chromatography, etc., or can be treated with a pharmacologically acceptable acid and purified as an acid addition salt by recrystallization or chromatography. .
本発明に従って前記置換ピリジル酢酸誘導体の酸付加塩
を製造するのに使用される酸としては、例えば塩酸、臭
化水素酸、硫酸、リン酸、過塩素酸などの無機酸、酢酸
、シュウ酸、クエン酸、乳酸、マレイン酸、コハク酸、
フマル酸、酒石酸、グルコン酸、マンデル酸、メタンス
ルホン酸などの有機酸をあげることができる。The acids used to prepare the acid addition salts of the substituted pyridyl acetic acid derivatives according to the invention include, for example, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, perchloric acid, acetic acid, oxalic acid, citric acid, lactic acid, maleic acid, succinic acid,
Organic acids such as fumaric acid, tartaric acid, gluconic acid, mandelic acid, and methanesulfonic acid can be mentioned.
本発明に従った置換ピリジル酢酸誘導体の別の合成法と
しては、前記の一般式(II)を有する化合物を有機溶
媒にとかし、0℃以下の温度で塩基で処理する。かかる
有機溶媒としてはエーテル系溶媒または芳香族炭化水素
系溶媒を使用するのが好ましい、また前記反応に用いら
れる塩基の使用量には特に限定はないが、好ましくは前
記一般式(II)の化合物に対し1.0〜1.2当量で
使用する。Another method for synthesizing substituted pyridyl acetic acid derivatives according to the invention is to dissolve the compound having the general formula (II) above in an organic solvent and treat it with a base at a temperature below 0°C. As such an organic solvent, it is preferable to use an ether solvent or an aromatic hydrocarbon solvent, and although there is no particular limitation on the amount of the base used in the reaction, it is preferable to use the compound of general formula (II) above. It is used in an amount of 1.0 to 1.2 equivalents.
かかる塩基としてはアルキルリチウム試薬水素化ナトリ
ウム、ナトリウムアルコキシド、カリウムアルコキシド
、ナトリウムアミドまたは金属ナトリウムなどを用いる
のが好ましい。As such a base, it is preferable to use an alkyl lithium reagent such as sodium hydride, sodium alkoxide, potassium alkoxide, sodium amide or metallic sodium.
次いで上記反応液に一般式(V)
S=C=N−R3(V)
(式中、R3は炭素数1〜5のアルキル基、またはフェ
ニル基を示す)で表わされるイソチオシアネートを加え
ることにより一般式(Im)C:S
NH−R”
(式中、R1およびR3は上に定義した通りである)で
表わされる本発明化合物を得ることができる。このよう
にして得られた化合物(Im)は、また、前述の如き精
製法を用いて精製することも出来るし、前述の如く医薬
として適当な酸と処理して酸付加塩とすることも出来る
。Then, by adding an isothiocyanate represented by the general formula (V) S=C=N-R3(V) (in the formula, R3 represents an alkyl group having 1 to 5 carbon atoms or a phenyl group) to the above reaction solution. A compound of the present invention represented by the general formula (Im)C:SNH-R'' (wherein R1 and R3 are as defined above) can be obtained.The compound thus obtained (Im ) can also be purified using the purification method described above, or can be treated with a pharmaceutically suitable acid to form an acid addition salt as described above.
本発明に従った前記一般式(I)で表わされる新規な置
換ピリジル酢酸誘導体は、それ自体投与してもよいが、
公知の製剤手法を利用して各種の剤形にすることができ
る0例えば、経口的に投与する場合には、通常、錠剤、
散剤、顆粒剤、カプセル剤、シロップ剤などで、又非経
口的投与の場合には注射剤、坐剤等として製剤化される
。いずれの場合にも、製剤上常用される公知の液体もし
くは固体の稀釈剤もしくは担体と混合して種々の形状の
製剤にすることができる。The novel substituted pyridyl acetic acid derivative represented by the general formula (I) according to the present invention may be administered as such, but
For example, when administered orally, tablets,
It is formulated into powders, granules, capsules, syrups, etc., and in the case of parenteral administration, it is formulated as injections, suppositories, etc. In either case, it can be mixed with a known liquid or solid diluent or carrier commonly used in pharmaceutical preparations to form preparations in various shapes.
このような稀釈剤もしくは担体の例としては、例えばポ
リビニルピロリドン、アラビアゴム、ゼラチン、ソルビ
ット、トラガカント、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、ポリビニルアルコール、
シリカ、乳糖、結晶セルロース、砂糖、澱粉、リン酸カ
ルシウム、植物油、カルボキシメチルセルロースカルシ
ウム、ラウリル硫酸ナトリウム、水、エタノール、グリ
セリン、マンニトール、シロップなどを例示することが
できる。Examples of such diluents or carriers include, for example, polyvinylpyrrolidone, gum arabic, gelatin, sorbitol, tragacanth, magnesium stearate, talc, polyethylene glycol, polyvinyl alcohol,
Examples include silica, lactose, crystalline cellulose, sugar, starch, calcium phosphate, vegetable oil, carboxymethyl cellulose calcium, sodium lauryl sulfate, water, ethanol, glycerin, mannitol, syrup, and the like.
本発明の消化性潰瘍治療剤は、一般式(りで表わされる
化合物もしくはその薬理学上許容される酸付加塩をその
有効量で含有することができる。The peptic ulcer therapeutic agent of the present invention can contain an effective amount of a compound represented by the general formula (R) or a pharmacologically acceptable acid addition salt thereof.
本発明の消化性潰瘍治療剤の有効投与量は、種々の要因
、例えば、治療すべき患者の症状、年令、投与経路、剤
形、投与回数などにより適宜に変更できるが、通常、成
人1日当り約50〜2,000mg、好ましくは100
〜1,000mgの範囲を例示することができる。The effective dosage of the peptic ulcer therapeutic agent of the present invention can be changed as appropriate depending on various factors, such as the symptoms of the patient to be treated, age, route of administration, dosage form, number of administrations, etc. Approximately 50-2,000 mg per day, preferably 100 mg
A range of 1,000 mg to 1,000 mg can be exemplified.
以下、参考例および実施例に従って、本発明をさらに詳
細に説明するが、本発明をこれら実施例に限定するもの
でないことはいうまでもない。Hereinafter, the present invention will be explained in more detail with reference to Reference Examples and Examples, but it goes without saying that the present invention is not limited to these Examples.
豊1妻1ニニi
トぷり1え
水20社に濃硫酸16−1および(3−メチル−2−ピ
リジル)アセトニトリル17.00. (I28,6ミ
リモル0を加え、3時間加熱還流した。放冷後、水を減
圧留去し、次いで残渣にエタノール10Dst’を加え
さらに1時同加熱還流した。エタノールを留去した後、
残渣を氷水中に注いだ0反応混合物を水酸化ナトリウム
で中和した後、クロロホルムで抽出した。抽出液を乾燥
後、溶媒留去し、残渣を減圧蒸留して標記化合物12.
91.を得た。Yutaka 1 Tsuma 1 Ni Ni Topuri 1 Water 20 companies Concentrated sulfuric acid 16-1 and (3-methyl-2-pyridyl) acetonitrile 17.00. (I28.6 mmol 0 was added and heated under reflux for 3 hours. After cooling, water was distilled off under reduced pressure. Next, 10 Dst' of ethanol was added to the residue and heated under reflux for an additional hour. After ethanol was distilled off,
The residue was poured into ice water, the reaction mixture was neutralized with sodium hydroxide, and then extracted with chloroform. After drying the extract, the solvent was distilled off, and the residue was distilled under reduced pressure to obtain the title compound 12.
91. I got it.
上記方法で、(3−メチル−2−ピリジル)アセトニト
リルの代わりに
(4−メチル−2−ピリジル)アセトニトリル(参考例
2)、
(5−メチル−2−ピリジル)アセトニトリル(参考例
3)、
(6−メチル−2−ピリジル)アセトニトリル(参考例
4)、
(4,6−シメチルー2−ピリジル)アセトニトリル(
参考例5)、
(4−メトキシ−3−メチル−2−ピリジル)アセトニ
トリル(参考例6)、
(4−メトキシ−6−メチル−2−ピリジル)アセトニ
トリル(参考例7)、
または
(6−メチル−4−(2,2,2−)リフルオロエトキ
シ)−2−ピリジル)アセトニトリル(参考例8)、
を用いることにより、それぞれ、
エチル (4−メチル−2−ピリジル)アセテート(参
考例2・)、
エチル (5−メチル−2−ピリジル)アセテート(参
考例3)、
エチル (6−メチル−2−ピリジル)アセテート(参
考例4)、
エチル (4,6−シメチルー2−ピリジル)アセテー
ト(参考例5)、
エチル (4−メトキシ−3−メチル−2−ピリジル)
アセテート(参考15i16)、エチル (4−メトキ
シ−6−メチル−2−ピリジル)アセテート(参考例7
)、
または
エチル 〔6−メチル−4−(2,2,2−トリフルオ
ロエトキシ)−2−ピリジルコアセテート(参考例8)
、
を得た。In the above method, instead of (3-methyl-2-pyridyl)acetonitrile, (4-methyl-2-pyridyl)acetonitrile (Reference Example 2), (5-methyl-2-pyridyl)acetonitrile (Reference Example 3), ( 6-Methyl-2-pyridyl)acetonitrile (Reference Example 4), (4,6-cymethyl-2-pyridyl)acetonitrile (
Reference Example 5), (4-methoxy-3-methyl-2-pyridyl)acetonitrile (Reference Example 6), (4-methoxy-6-methyl-2-pyridyl)acetonitrile (Reference Example 7), or (6-methyl -4-(2,2,2-)lifluoroethoxy)-2-pyridyl)acetonitrile (Reference Example 8), and ethyl (4-methyl-2-pyridyl)acetate (Reference Example 2), respectively. ), Ethyl (5-methyl-2-pyridyl) acetate (Reference example 3), Ethyl (6-methyl-2-pyridyl) acetate (Reference example 4), Ethyl (4,6-dimethyl-2-pyridyl) acetate (Reference example) Example 5), ethyl (4-methoxy-3-methyl-2-pyridyl)
Acetate (Reference 15i16), Ethyl (4-methoxy-6-methyl-2-pyridyl) acetate (Reference Example 7)
), or ethyl [6-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl coacetate (Reference Example 8)
, got .
また、上記方法でエタノールの代わりにアミルアルコー
ルを用いることによりアミル (3−メチル−2−ピリ
ジル)アセテート(参考例9)を得た。Moreover, amyl (3-methyl-2-pyridyl) acetate (Reference Example 9) was obtained by using amyl alcohol instead of ethanol in the above method.
上記各化合物の物性データ及び収率を第1表に示す、
。The physical property data and yield of each of the above compounds are shown in Table 1.
.
t!JLu東づl
二上!澱1
水10社に濃硫酸8WAl、(5−メチル−2−ピリジ
ル)アセトニトリル8.5g(64,3ミリモル)を加
え、3時間加熱還流した。放冷後、水酸化ナトリウム水
溶液で中和し、水を留去した。残渣をベンゼンで共沸し
て、完全に水分を除去した後、ピリジン25社、塩化メ
チレン50社次いで、ゲラニオール9.9g(64,3
ミリモル)、1−エチル−3−(3−ジメチルアミノプ
ロピル)カルボジイミド塩酸塩18.49g(98,5
ミリモル)を加え、室温にて3時間撹拌した。溶媒を留
去した後、水で希釈し、クロロホルムで抽出した。抽出
液を乾燥後、溶媒留去し、残渣をシリカゲルクロマトグ
ラフィーに付し標記化合物17.8.を得た。T! JLu East Zul Futami! 8 WAl of concentrated sulfuric acid and 8.5 g (64.3 mmol) of (5-methyl-2-pyridyl)acetonitrile were added to 10 pieces of water and heated under reflux for 3 hours. After cooling, the mixture was neutralized with an aqueous sodium hydroxide solution, and water was distilled off. After completely removing water by azeotroping the residue with benzene, 25 g of pyridine, 50 g of methylene chloride, and 9.9 g of geraniol (64,3 g) were added.
mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride 18.49 g (98,5
mmol) and stirred at room temperature for 3 hours. After evaporating the solvent, it was diluted with water and extracted with chloroform. After drying the extract, the solvent was distilled off, and the residue was subjected to silica gel chromatography to obtain the title compound 17.8. I got it.
上記方法で、(5−メチル−2−ピリジル)アセトニト
リルの代わりに
(6−メチル−2−ピリジル)アセトニトリル(参考例
11)
(4,6−シメチルー2− ピリジル)アセトニトリル
(参考例12)
(4−メトキシ−3−メチル−2−ピリジル)アセトニ
トリル(参考例13)
(4−メトキシ−6−メチル−2−ピリジル)アセトニ
トリル(参考例14)゛
または
(6−メチル−4−(2、2、2−トリフルオロエトキ
シ)−2−ピリジル)アセトニトリル(参考例を用いる
ことにより
ゲラニル (6−メチル−2−ピリジル)アセテート(
参考例11)
ゲラニル (4,6−シメチルー2−)ピリジル)アセ
テート(参考例12)
ゲラニル (4−メトキシ−3−メチル−2−ピリジル
)アセテート(参考例13)
ゲラニル (4−メトキシ−6−メチル−2−ピリジル
)アセテート(参考例14)
または
ゲラニル 〔6−メチル−4−(2,2,2−トリフル
オロエトキシ)−2−ピリジルコアセテート(参考例1
5)
を得た。In the above method, instead of (5-methyl-2-pyridyl)acetonitrile, (6-methyl-2-pyridyl)acetonitrile (Reference Example 11) (4,6-cymethyl-2-pyridyl)acetonitrile (Reference Example 12) (4 -Methoxy-3-methyl-2-pyridyl)acetonitrile (Reference Example 13) (4-Methoxy-6-methyl-2-pyridyl)acetonitrile (Reference Example 14) or (6-methyl-4-(2,2, 2-trifluoroethoxy)-2-pyridyl)acetonitrile (by using the reference example, geranyl (6-methyl-2-pyridyl)acetate (
Reference example 11) Geranyl (4,6-cymethyl-2-)pyridyl) acetate (Reference example 12) Geranyl (4-methoxy-3-methyl-2-pyridyl) acetate (Reference example 13) Geranyl (4-methoxy-6- Methyl-2-pyridyl) acetate (Reference Example 14) or geranyl [6-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl coacetate (Reference Example 1)
5) Obtained.
また上記参考例14の方法において、ゲラニオールの代
わりにプレニルアルコールを用いることによりプレニル
(4−メトキシ−6−メチル−2−ピリジル)アセテ
ートを得(参考例16)、さらに上記(参考例10)方
法においてゲラニオールの代わりにファルネソールを用
い、また5−メチル−2−ピリジルアセトニトリルの代
わりに、3−メチル−2−ピリジルアセトニトリルを用
いることによりファルネシル (3−メチル−2−ピリ
ジル)アセテートを得た(参考例17)。Further, in the method of Reference Example 14 above, prenyl (4-methoxy-6-methyl-2-pyridyl) acetate was obtained by using prenyl alcohol instead of geraniol (Reference Example 16), and further by the method of the above (Reference Example 10). Farnesyl (3-methyl-2-pyridyl) acetate was obtained by using farnesol instead of geraniol and using 3-methyl-2-pyridylacetonitrile instead of 5-methyl-2-pyridylacetonitrile (Reference Example 17).
上記各化合物の物性データ及び収率を第1表に示す。Table 1 shows the physical property data and yield of each of the above compounds.
1五へ魚腹
エチル (4−メチル−2−ピリジル)アセテート2.
20g (I2,4ミリモル)を2%NaOR水溶液5
0に加え、室温にて12時間撹拌した。反応溶液を塩酸
水溶液で中和したのち、溶媒を留去した。残渣をベンゼ
ンで共沸して、完全に水分を除去したのち、ピリジン1
0mf、塩化メチレン100社次いでゲラニオール1.
91g (I2,4ミリモル)、1−エチル−3−(3
−ジメチルアミノ10ピル)カルボジイミド塩酸塩4.
フ5. (24,8ミリモル)を加え、室温にて3時間
撹拌した。水で希釈し、塩化メチレンで抽出した。抽出
液を乾燥後、溶媒を留去し、残渣をシリカゲルクロマト
グラフィーに付し、橿記化合物を2.50g得た。1.5 fish belly ethyl (4-methyl-2-pyridyl) acetate 2.
20 g (I2.4 mmol) in 2% NaOR aqueous solution 5
0 and stirred at room temperature for 12 hours. After neutralizing the reaction solution with an aqueous hydrochloric acid solution, the solvent was distilled off. After azeotropically distilling the residue with benzene to completely remove water, pyridine 1
0mf, methylene chloride 100 companies, then geraniol 1.
91 g (I2.4 mmol), 1-ethyl-3-(3
-dimethylamino 10 pyru) carbodiimide hydrochloride 4.
F5. (24.8 mmol) was added and stirred at room temperature for 3 hours. Diluted with water and extracted with methylene chloride. After drying the extract, the solvent was distilled off, and the residue was subjected to silica gel chromatography to obtain 2.50 g of the above compound.
得られた化合物の物性データ及び収率を第1表に示す。Table 1 shows the physical property data and yield of the obtained compound.
以下余白
塞JLLL
T皇f−1プシ1え
ゲラニル 2−(4−メトキシ−6−メチル)ピリジル
アセテート5.0Og (I5,8ミリモル)を無水テ
トラヒドロフラン50社に加え、窒素気流下、−78℃
にて、15%n−ブチルリチウムヘキラン溶液10.4
mt’を滴下した。15分間撹拌後、メザルイソチオシ
アネート、1.27g (I7,3ミリモル)を加え、
さらに、室温で1.5時間撹拌した0反応3合物を塩化
アンモニウム水溶液で希釈し、クロロホルムで抽出しな
、抽出液を乾燥後、溶媒留去し、残渣をシリカゲルクロ
マトグラフィーに付し、目的化合物4.67gを得な、
得られた化合物の物性データ及び収率を第2表に示す。5.0 Og (I5.8 mmol) of geranyl 2-(4-methoxy-6-methyl)pyridyl acetate was added to 50% of anhydrous tetrahydrofuran at -78°C under a nitrogen stream.
15% n-butyllithium hexane solution 10.4
mt' was added dropwise. After stirring for 15 minutes, 1.27 g (I7.3 mmol) of mezal isothiocyanate was added,
Furthermore, the reaction mixture 3, which had been stirred at room temperature for 1.5 hours, was diluted with an aqueous ammonium chloride solution and extracted with chloroform. After drying the extract, the solvent was distilled off, and the residue was subjected to silica gel chromatography. Obtain 4.67 g of the compound.
Table 2 shows the physical property data and yield of the obtained compound.
用して反応させて第2表に示す目的化合物を合成した。The target compounds shown in Table 2 were synthesized by reacting with the following compounds.
得られた化合物の物性データ及び収率を第2表に示す。Table 2 shows the physical property data and yield of the obtained compound.
2− ルバモイルアセテートのム 曲。2- Rubamoyl acetate song.
ゲラニル (5−メチル−2−ピリジル)アセテ−)2
.60g(9,05ミリモル)を無水テトラヒドロフラ
ン25m1に加え、窒素気流下−78℃にて、15%η
−ブチルリチウムヘキサン溶液6.2−jFを加えた。Geranyl (5-methyl-2-pyridyl)acetate)2
.. 60 g (9.05 mmol) was added to 25 ml of anhydrous tetrahydrofuran and heated to 15% η at -78°C under a nitrogen stream.
-Butyllithium hexane solution 6.2-jF was added.
15分間撹拌後、二硫化炭素0.76g(9,95ミリ
モル)を加えさらに15分間同温度で撹拌した。After stirring for 15 minutes, 0.76 g (9.95 mmol) of carbon disulfide was added, and the mixture was stirred for an additional 15 minutes at the same temperature.
次にヨウ化メチル1.35g (9,50ミリモル)を
加え、室温で1時間撹拌した0反応混合物を塩化アンモ
ニウム飽和水溶液で希釈しクロロホルムで抽出した。抽
出液を覧燥後、溶媒留去し残渣をシリカゲルクロマトグ
ラフィーに付しゲラニル 2−ジチオメトキシカルボニ
ル−2−(2−ピリジル)アセテートを黄色油状物とし
て2.80g (5,45ミリモル)得た。Next, 1.35 g (9.50 mmol) of methyl iodide was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with a saturated aqueous ammonium chloride solution and extracted with chloroform. After drying the extract, the solvent was distilled off and the residue was subjected to silica gel chromatography to obtain 2.80 g (5.45 mmol) of geranyl 2-dithiomethoxycarbonyl-2-(2-pyridyl) acetate as a yellow oil. .
これをエタノール3mlに溶解させ、これに28%アン
モニア水0.68−ffi(5,45ミリモル)を加え
、室でX
しな、抽出液を乾燥後、溶媒留去し、残渣をシリカゲル
クロマトグラフィーに付し、目的化合物1.35.を得
た。得られた化合物の物性データ及び収率を第2表に示
す。This was dissolved in 3 ml of ethanol, 0.68-ffi (5.45 mmol) of 28% aqueous ammonia was added thereto, and the extract was dried at room temperature, the solvent was distilled off, and the residue was subjected to silica gel chromatography. The target compound 1.35. I got it. Table 2 shows the physical property data and yield of the obtained compound.
実施例5の方法に従って、適当な出発化合物を使用して
反応させて第2表に示す目的化合物を合成した。According to the method of Example 5, appropriate starting compounds were reacted to synthesize the target compounds shown in Table 2.
得られた化合物の物性データ及び収率を第2表に示す。Table 2 shows the physical property data and yield of the obtained compound.
乳糖 25 結晶セルロース 10 トウモロコシデンプン 100 上記成分を公知の方法に準じて製剤とした。Lactose 25 Crystalline cellulose 10 Corn starch 100 The above ingredients were prepared into a formulation according to a known method.
以下余e
本発明化合物の薬理効果について以下の試験を行ない、
胃酸分泌抑制効果および胃粘膜保護作用を確認した。ま
た、毒性は一群6匹のマウスを用い試験化合物を経口で
投与し、その毒性(LDso)を求めた。The following tests were conducted on the pharmacological effects of the compounds of the present invention,
The effect of suppressing gastric acid secretion and protecting the gastric mucosa was confirmed. In addition, the toxicity (LDso) was determined by orally administering the test compound to a group of 6 mice.
体重200−240.のスプラーグドウリ4 (Spr
agu6−Dawley)系雄性ラットを24時時間給
(水は自由に与えた)して使用した。エーテル麻酔下に
開腹し、幽門部を結紮後閉腹しで、4時間給食絶木下に
放置した。エーテル麻酔下に胃を摘出し、胃液を採取し
た。採取した胃液は30GOrpmで10分間遠沈し、
上澄液の、容量(社)を測定した後、胃液の1m&を0
.1規定水酸化ナトリウム溶液でpHフ、0まで滴定し
て酸度(μEg/sf)を求めた。さらに胃液量と酸度
の積より酸排出量(μEg/ 4 h )を求め;下式
より抑制率を求め、ついで、抑制率を投与量(sg/k
g)に対して半対数グラフにプロットして、ED5゜値
を求めた。被験薬はいずれも生理食塩液にて懸濁し、0
.2社/100g体重の割合で幽門結紮直後、−二指腸
内に投与した。Weight 200-240. Sprague Dowry 4 (Spr.
Male rats of the agu6-Dawley strain were used and fed 24 hours a day (water was provided ad libitum). The abdomen was opened under ether anesthesia, the pylorus was ligated, the abdomen was closed, and the animal was left without food for 4 hours. The stomach was removed under ether anesthesia and gastric juice was collected. The collected gastric juice was centrifuged at 30 GO rpm for 10 minutes,
After measuring the volume of the supernatant, 1 m& of gastric juice was
.. The pH was titrated to 0 with a 1N sodium hydroxide solution to determine acidity (μEg/sf). Furthermore, the acid excretion amount (μEg/4 h) is calculated from the product of the gastric juice volume and the acidity; the suppression rate is calculated from the formula below, and then the suppression rate is expressed as the dose (sg/k).
g) was plotted on a semi-log graph to determine the ED5° value. All test drugs were suspended in physiological saline and
.. It was administered into the duodenum immediately after pyloric ligation at a ratio of 2 companies/100 g body weight.
結果は第3表に示した通りである。The results are shown in Table 3.
2、塩 エタノール゛ 9 る
体重200−240gのスプラーグードウリイ(Spr
ague−D@wley)系雄性ラットを24時時間給
して使用した。このラットに150ミリモル塩酸を含む
60%エタノール溶液を0.5m1/100g・体重の
容量で経口投与し、一時間後にエーテル麻酔下に胃を、
摘出した。胃内に10dの2%ホルマリン溶液を注入し
、さらに2%ホルマリン溶液中に約15分間浸し、胃内
外壁を固定した。大弯に沿って切開し、10倍の実体顕
微鏡下、腺胃部に発生している損傷の長さを計測し、−
6当たりの胃粘膜損傷の長さの合計を潰瘍係数(Ies
ion 1ndex)(鍮輪)として対照群と比較し
、下式によって抑制率を算出し、ついで、この抑制率を
投与量(mg/kg)に対して半対数グラフにプロット
して、ED、。値を求めた。被験薬はいずれも生理食塩
液に懸濁し、0、5 ml/ 100g・体重の容量で
、塩酸エタノール溶液投与30分前に経口投与した。2. Sprague-Dawley (Spr.
Ague-D@wley) male rats were used and fed 24 hours a day. A 60% ethanol solution containing 150 mmol hydrochloric acid was orally administered to the rat in a volume of 0.5 ml/100 g/body weight, and one hour later, the stomach was injected under ether anesthesia.
Extracted. 10 days of 2% formalin solution was injected into the stomach, and the mice were further immersed in the 2% formalin solution for about 15 minutes to fix the inner and outer walls of the stomach. An incision was made along the greater curvature, and the length of the damage occurring in the glandular stomach was measured under a stereomicroscope at 10x magnification.
The sum of the lengths of gastric mucosal damage per 6 points is the ulcer index (Ies
ion 1 index) (brass ring), the inhibition rate was calculated using the following formula, and this inhibition rate was then plotted on a semi-logarithmic graph against the dose (mg/kg) to determine the ED. I found the value. All test drugs were suspended in physiological saline and orally administered in a volume of 0.5 ml/100 g body weight 30 minutes before administration of the hydrochloric acid ethanol solution.
結果は第3表に示した通りである。The results are shown in Table 3.
第3表Table 3
Claims (1)
▲数式、化学式、表等があります▼ (式中、nは1〜5の整数を表わす)を示し、R^2は
、水素原子、炭素数1〜5のアルキル基またはフェニル
基を示し、X^1およびX^2は、独立に、水素原子、
炭素数1〜5の低級アルキル基、炭素数1〜5の低級ア
ルコキシ基または、炭素数1〜5のハロゲン置換低級ア
ルコキシ基のいずれかを示す(但し、X^1およびX^
2が共に水素原子である場合は除く)〕 で表わされる置換ピリジル酢酸誘導体またはその薬理学
的に許容される酸付加塩。 2、一般式( I ) ▲数式、化学式、表等があります▼( I ) 〔式中、R^1は炭素数1〜5のアルキル基または基▲
数式、化学式、表等があります▼ (式中、nは1から5の整数を表わす)を示し、R^2
は水素原子、炭素数1〜5のアルキル基またはフェニル
基を示し、X^1およびX^2は、独立に、水素原子、
炭素数1〜5の低級アルキル基、炭素数1〜5の低級ア
ルコキシ基または炭素数1〜5のハロゲン置換低級アル
コキシ基のいずれかを示す(但し、X^1およびX^2
が共に水素原子である場合を除く)〕 で表わされる置換ピリジル酢酸誘導体またはその薬理学
上許容される酸付加塩を有効成分として含有する消化性
潰瘍治療剤。[Claims] 1. General formula (I) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) [In the formula, R^1 is an alkyl group having 1 to 5 carbon atoms, or a group ▲ Numerical formula, chemical formula, There are tables etc. ▼ (In the formula, n represents an integer from 1 to 5), R^2 represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a phenyl group, and X^1 and X^ 2 is independently a hydrogen atom,
Indicates either a lower alkyl group having 1 to 5 carbon atoms, a lower alkoxy group having 1 to 5 carbon atoms, or a halogen-substituted lower alkoxy group having 1 to 5 carbon atoms (however, X^1 and X^
2 is a hydrogen atom)] A substituted pyridyl acetic acid derivative or a pharmacologically acceptable acid addition salt thereof. 2. General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R^1 is an alkyl group or group having 1 to 5 carbon atoms▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ (in the formula, n represents an integer from 1 to 5), R^2
represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or a phenyl group, and X^1 and X^2 are independently a hydrogen atom,
Represents either a lower alkyl group having 1 to 5 carbon atoms, a lower alkoxy group having 1 to 5 carbon atoms, or a halogen-substituted lower alkoxy group having 1 to 5 carbon atoms (however, X^1 and X^2
are both hydrogen atoms)] A therapeutic agent for peptic ulcer disease containing a substituted pyridyl acetic acid derivative represented by the following or a pharmacologically acceptable acid addition salt thereof as an active ingredient.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP6418687A JPS63230670A (en) | 1987-03-20 | 1987-03-20 | Substituted pyridiylacetic acid derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP6418687A JPS63230670A (en) | 1987-03-20 | 1987-03-20 | Substituted pyridiylacetic acid derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS63230670A true JPS63230670A (en) | 1988-09-27 |
Family
ID=13250776
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP6418687A Pending JPS63230670A (en) | 1987-03-20 | 1987-03-20 | Substituted pyridiylacetic acid derivative |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS63230670A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009030450A2 (en) | 2007-09-03 | 2009-03-12 | Syngenta Limited | Novel herbicides |
EP2527333A1 (en) | 2007-06-28 | 2012-11-28 | Syngenta Limited | Pyrandione, thiopyrandione and cyclohexanetrione compounds having herbicidal properties |
JP5515078B2 (en) * | 2007-08-31 | 2014-06-11 | 学校法人福岡大学 | Ischemic injury inhibitor |
-
1987
- 1987-03-20 JP JP6418687A patent/JPS63230670A/en active Pending
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2527333A1 (en) | 2007-06-28 | 2012-11-28 | Syngenta Limited | Pyrandione, thiopyrandione and cyclohexanetrione compounds having herbicidal properties |
JP5515078B2 (en) * | 2007-08-31 | 2014-06-11 | 学校法人福岡大学 | Ischemic injury inhibitor |
WO2009030450A2 (en) | 2007-09-03 | 2009-03-12 | Syngenta Limited | Novel herbicides |
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