JPH0525172A - 1,8-naphthyridine derivative, its production and antiulcer agent containing the same - Google Patents
1,8-naphthyridine derivative, its production and antiulcer agent containing the sameInfo
- Publication number
- JPH0525172A JPH0525172A JP3202260A JP20226091A JPH0525172A JP H0525172 A JPH0525172 A JP H0525172A JP 3202260 A JP3202260 A JP 3202260A JP 20226091 A JP20226091 A JP 20226091A JP H0525172 A JPH0525172 A JP H0525172A
- Authority
- JP
- Japan
- Prior art keywords
- naphthyridine
- naphthyridin
- dimethyl
- methyl
- 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.)
- Pending
Links
- 239000003699 antiulcer agent Substances 0.000 title claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 150000005058 1,8-naphthyridines Chemical class 0.000 title claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 7
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- -1 1,5-dimenthyl-1,8- naphthyridin-2(1H)-one Chemical compound 0.000 abstract description 124
- 150000001875 compounds Chemical class 0.000 abstract description 39
- 230000001681 protective effect Effects 0.000 abstract description 10
- 230000027119 gastric acid secretion Effects 0.000 abstract description 8
- 230000002496 gastric effect Effects 0.000 abstract description 7
- 229910052794 bromium Inorganic materials 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 150000004820 halides Chemical class 0.000 abstract 1
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
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- 238000002360 preparation method Methods 0.000 description 3
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
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- 241001465754 Metazoa Species 0.000 description 2
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- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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- 238000010998 test method Methods 0.000 description 2
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- YPYHDJXCSUBQLK-UHFFFAOYSA-N 1,5-dimethyl-1,8-naphthyridin-2-one Chemical compound CN1C(=O)C=CC2=C1N=CC=C2C YPYHDJXCSUBQLK-UHFFFAOYSA-N 0.000 description 1
- WWWOSHGSCWSTNT-UHFFFAOYSA-N 1-ethyl-5,7-dimethyl-1,8-naphthyridin-2-one Chemical compound CC1=CC(C)=C2C=CC(=O)N(CC)C2=N1 WWWOSHGSCWSTNT-UHFFFAOYSA-N 0.000 description 1
- YXNUNBPAJCPUDJ-UHFFFAOYSA-N 1-ethyl-7-methyl-1,8-naphthyridin-2-one Chemical compound CCN1C(=O)C=CC2=C1N=C(C=C2)C YXNUNBPAJCPUDJ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000004185 liver Anatomy 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
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920001289 polyvinyl ether Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000002417 xiphoid bone Anatomy 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は新規な１，８−ナフチリ
ジン誘導体またはその医薬的に許容される塩、その製造
法及びそれを含有する抗潰瘍剤に関し、詳しくは胃酸分
泌阻害作用と胃粘膜保護作用を有する新規な１，８−ナ
フチリジン誘導体またはその医薬的に許容される塩、そ
の製造法及びそれを有効成分として含有する抗潰瘍薬剤
に関する。FIELD OF THE INVENTION The present invention relates to a novel 1,8-naphthyridine derivative or a pharmaceutically acceptable salt thereof, a method for producing the same and an antiulcer agent containing the same, and more specifically to gastric acid secretion inhibitory action and gastric mucosa. The present invention relates to a novel 1,8-naphthyridine derivative having a protective action or a pharmaceutically acceptable salt thereof, a method for producing the same, and an antiulcer drug containing the same as an active ingredient.
【０００２】[0002]
【従来の技術】胃・十二指腸潰瘍などの消化性潰瘍は、
酸やペプシンなどのいわゆる攻撃因子と、胃粘膜保護作
用や粘液合成促進作用、さらには胃粘膜血流量などのい
わゆる防御因子とのバランスがくずれて起こる自己消化
性の疾患であると説明されている。消化性潰瘍の治療は
現在では内科的治療が一般的であり、種々の薬物療法が
試みられている。現在最も使用されている抗潰瘍剤とし
ては、ヒスタミンＨ2 受容体拮抗作用に基づくシメチジ
ン（Cimetidine），ラニチジン（Ranitidine）などの所
謂Ｈ2 −ブロッカーを挙げることができる。しかし、こ
れらの薬剤は、副作用として抗アンドロゲン作用，肝臓
の代謝酵素阻害作用などが報告されている。2. Description of the Related Art Peptic ulcers such as gastric and duodenal ulcers
It is explained that it is a self-digestive disease that occurs when the so-called attack factors such as acid and pepsin are out of balance with the so-called protective factors such as gastric mucosa protective action and mucus synthesis promoting action and gastric mucosal blood flow. . Currently, medical treatment for peptic ulcer is generally medical treatment, and various drug therapies have been tried. The most used antiulcer agents at present include so-called H 2 -blockers such as cimetidine and ranitidine based on histamine H 2 receptor antagonistic action. However, these drugs have been reported to have anti-androgen action, liver metabolizing enzyme inhibitory action and the like as side effects.
【０００３】最近、胃壁細胞に存在するＨ+ −Ｋ+ −ア
デノシントリホスファターゼの阻害剤が優れた胃酸分泌
抑制剤となり得ることが報告されており（実験医学第５
巻、第１２号、１１７１頁〜１１７７頁（１９８
７））、例えば「オメプラゾール」（特開昭５４−１４
１７８３号）や特開昭５９−１８２７７号，特開昭６１
−２４５８９号，特開昭６４−７９１７７号等の公報記
載の化合物を挙げることができる。しかしながら、これ
らＨ2 −ブロッカーやＨ+ −Ｋ+ −アデノシントリホス
ファターゼ阻害剤は、防御因子の増強という観点から
は、何ら著明な効果を示さない。Recently, present in gastric parietal cells H + -K + - that inhibitors of adenosine triphosphatase obtain an excellent gastric acid secretion inhibitor has been reported (Experimental Medicine 5
Volume 12, Issue 1171-1177 (198
7)), for example, "omeprazole" (JP-A-54-14)
1783), JP-A-59-18277 and JP-A-61.
The compounds described in JP-A No. 24589 and JP-A No. 64-79177 can be mentioned. However, these H 2 - blockers and H + -K + - ATPase inhibitor, from the viewpoint of enhancing protective factor, not show any significant effect.
【０００４】ところで、当該研究分野においては、胃酸
分泌抑制作用と胃粘膜保護作用の両方を有する物質の探
求も行なわれており、例えば特開昭６１−４０２８７
号，特開昭６２−１５８２８１号，特開昭６２−２２８
０７６号公報記載の化合物などを挙げることができる。By the way, in the field of research, there is also a search for a substance having both a gastric acid secretion inhibitory action and a gastric mucosal protective action, for example, Japanese Patent Laid-Open No. 61-40287.
JP-A-62-158281, JP-A-62-228
Examples thereof include the compounds described in JP-A-076.
【０００５】[0005]
【発明が解決しようとする課題】本発明の目的は、胃酸
分泌抑制作用と胃粘膜保護作用の両方を具備し、かつ従
来知られている化合物よりも優れた抗潰瘍作用とより高
い安全性を有する化合物並びに該化合物の製造法を提供
することである。DISCLOSURE OF THE INVENTION The object of the present invention is to have both gastric acid secretion inhibitory action and gastric mucosal protective action, and to have an antiulcer action and higher safety superior to those of the conventionally known compounds. A compound having the same and a method for producing the compound are provided.
【０００６】[0006]
【課題を解決するための手段】かかる事情に鑑み、本発
明者らは胃酸分泌抑制作用と胃粘膜保護作用の両方を併
せもつ抗潰瘍剤を開発すべく鋭意検討してきたところ、
ある種の１，８−ナフチリジン誘導体がその目的を達成
することを見出して本発明を完成した。In view of the above circumstances, the present inventors have earnestly studied to develop an antiulcer agent having both a gastric acid secretion inhibitory action and a gastric mucosa protective action,
The present invention has been completed by the discovery that certain 1,8-naphthyridine derivatives achieve their purpose.
【０００７】すなわち、本発明は下記の一般式（Ｉ）That is, the present invention has the following general formula (I)
【化３】
（式中、Ｒ1 は低級アルキル基，低級アルケニル基，ア
ラルキル基を示す。Ｒ2 〜Ｒ4 は各々独立に水素原子ま
たは低級アルキル基，低級アルケニル基，アラルキル基
を示す。ただし、Ｒ2 〜Ｒ4 のすべてが同時に水素原子
ではありえない。）で表される化合物またはその医薬的
に許容される塩並びにその製造法を提供すると共に、そ
れを有効成分として含有する抗潰瘍剤を提供するもので
ある。[Chemical 3] (In the formula, R 1 represents a lower alkyl group, a lower alkenyl group, an aralkyl group .R 2 to R 4 each independently represent a hydrogen atom or a lower alkyl group, lower alkenyl group, an aralkyl group. However, R 2 ~ R 4 cannot all be hydrogen atoms at the same time) or a pharmaceutically acceptable salt thereof and a method for producing the same, and an antiulcer agent containing the same as an active ingredient. is there.
【０００８】本発明の化合物は、いずれも文献未収載の
新規化合物である。本発明の化合物において、上記一般
式（Ｉ）の定義における低級アルキル基とは、炭素数１
乃至６の直鎖あるいは分岐状のアルキル基（例えばメチ
ル基，エチル基，プロピル基，イソプロピル基，ブチル
基，イソブチル基，sec-ブチル基，tert- ブチル基，ペ
ンチル基，１−エチルプロピル基，３−メチルブチル
基，ヘキシル基などを挙げることができる。）であり、
低級アルケニル基とは、炭素数１乃至６の直鎖もしくは
分岐状アルケニル基（例えば２−プロペニル基，cis-ま
たはtrans-２−ブテニル基，３−ブテニル基，cis-また
はtrans-２−ペンテニル基，cis-またはtrans-３−ペン
テニル基，４−ペンテニル基，cis-またはtrans-２−ヘ
キセニル基，cis-またはtrans-３−ヘキセニル基などを
挙げることができる。）であり、またアラルキル基と
は、上述の低級アルキル基上にさらに芳香族炭化水素基
が置換したもの（例えばベンジル基，フェネチル基など
を挙げることができる。）である。The compounds of the present invention are all novel compounds which are not listed in the literature. In the compound of the present invention, the lower alkyl group in the above-mentioned definition of the general formula (I) has 1 carbon atoms.
To 6 straight-chain or branched alkyl groups (for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, 1-ethylpropyl group, 3-methylbutyl group, hexyl group and the like).
The lower alkenyl group is a linear or branched alkenyl group having 1 to 6 carbon atoms (for example, 2-propenyl group, cis- or trans-2-butenyl group, 3-butenyl group, cis- or trans-2-pentenyl group. , Cis- or trans-3-pentenyl group, 4-pentenyl group, cis- or trans-2-hexenyl group, cis- or trans-3-hexenyl group, etc.) and an aralkyl group Is the above-mentioned lower alkyl group further substituted with an aromatic hydrocarbon group (eg, a benzyl group, a phenethyl group, etc.).
【０００９】本発明に係る化合物の代表的なものとして
は、次の化合物が例示される。１，５−ジメチル−１，
８−ナフチリジン−２（１Ｈ）−オン、１，６−ジメチ
ル−１，８−ナフチリジン−２（１Ｈ）−オン、１，７
−ジメチル−１，８−ナフチリジン−２（１Ｈ）−オ
ン、１，５，６−トリメチル−１，８−ナフチリジン−
２（１Ｈ）−オン、１，５，７−トリメチル−１，８−
ナフチリジン−２（１Ｈ）−オン、１，６，７−トリメ
チル−１，８−ナフチリジン−２（１Ｈ）−オン、１，
５，６，７−テトラメチル−１，８−ナフチリジン−２
（１Ｈ）−オン、１−エチル−５−メチル−１，８−ナ
フチリジン−２（１Ｈ）−オン、Typical examples of the compound according to the present invention include the following compounds. 1,5-dimethyl-1,
8-naphthyridin-2 (1H) -one, 1,6-dimethyl-1,8-naphthyridin-2 (1H) -one, 1,7
-Dimethyl-1,8-naphthyridine-2 (1H) -one, 1,5,6-trimethyl-1,8-naphthyridine-
2 (1H) -one, 1,5,7-trimethyl-1,8-
Naphthyridin-2 (1H) -one, 1,6,7-trimethyl-1,8-naphthyridin-2 (1H) -one, 1,
5,6,7-Tetramethyl-1,8-naphthyridine-2
(1H) -one, 1-ethyl-5-methyl-1,8-naphthyridin-2 (1H) -one,
【００１０】１−エチル−６−メチル−１，８−ナフチ
リジン−２（１Ｈ）−オン、１−エチル−７−メチル−
１，８−ナフチリジン−２（１Ｈ）−オン、１−エチル
−５，６−ジメチル−１，８−ナフチリジン−２（１
Ｈ）−オン、１−エチル−５，７−ジメチル−１，８−
ナフチリジン−２（１Ｈ）−オン、１−エチル−６，７
−ジメチル−１，８−ナフチリジン−２（１Ｈ）−オ
ン、１−エチル−５，６，７−トリメチル−１，８−ナ
フチリジン−２（１Ｈ）−オン、５−メチル−１−プロ
ピル−１，８−ナフチリジン−２（１Ｈ）−オン、６−
メチル−１−プロピル−１，８−ナフチリジン−２（１
Ｈ）−オン、７−メチル−１−プロピル−１，８−ナフ
チリジン−２（１Ｈ）−オン、５，６−ジメチル−１−
プロピル−１，８−ナフチリジン−２（１Ｈ）−オン、
５，７−ジメチル−１−プロピル−１，８−ナフチリジ
ン−２（１Ｈ）−オン、６，７−ジメチル−１−プロピ
ル−１，８−ナフチリジン−２（１Ｈ）−オン、５，
６，７−トリメチル−１−プロピル−１，８−ナフチリ
ジン−２（１Ｈ）−オン、１−イソプロピル−５−メチ
ル−１，８−ナフチリジン−２（１Ｈ）−オン、１−イ
ソプロピル−６−メチル−１，８−ナフチリジン−２
（１Ｈ）−オン、１−イソプロピル−７−メチル−１，
８−ナフチリジン−２（１Ｈ）−オン、１−イソプロピ
ル−５，６−ジメチル−１，８−ナフチリジン−２（１
Ｈ）−オン、１−イソプロピル−５，７−ジメチル−
１，８−ナフチリジン−２（１Ｈ）−オン、１−イソプ
ロピル−６，７−ジメチル−１，８−ナフチリジン−２
（１Ｈ）−オン、１−イソプロピル−５，６，７−トリ
メチル−１，８−ナフチリジン−２（１Ｈ）−オン、１
−ブチル−５−メチル−１，８−ナフチリジン−２（１
Ｈ）−オン、１−ブチル−６−メチル−１，８−ナフチ
リジン−２（１Ｈ）−オン、１−ブチル−７−メチル−
１，８−ナフチリジン−２（１Ｈ）−オン、１−ブチル
−５，６−ジメチル−１，８−ナフチリジン−２（１
Ｈ）−オン、１−ブチル−５，７−ジメチル−１，８−
ナフチリジン−２（１Ｈ）−オン、１−ブチル−６，７
−ジメチル−１，８−ナフチリジン−２（１Ｈ）−オ
ン、１−ブチル−５，６，７−トリメチル−１，８−ナ
フチリジン−２（１Ｈ）−オン、１−イソブチル−５−
メチル−１，８−ナフチリジン−２（１Ｈ）−オン、１
−イソブチル−６−メチル−１，８−ナフチリジン−２
（１Ｈ）−オン、１−イソブチル−７−メチル−１，８
−ナフチリジン−２（１Ｈ）−オン、１−イソブチル−
５，６−ジメチル−１，８−ナフチリジン−２（１Ｈ）
−オン、１−イソブチル−５，７−ジメチル−１，８−
ナフチリジン−２（１Ｈ）−オン、１−イソブチル−
６，７−ジメチル−１，８−ナフチリジン−２（１Ｈ）
−オン、１−イソブチル−５，６，７−トリメチル−
１，８−ナフチリジン−２（１Ｈ）−オン、５−メチル
−１−（３−メチルブチル）−１，８−ナフチリジン−
２（１Ｈ）−オン、６−メチル−１−（３−メチルブチ
ル）−１，８−ナフチリジン−２（１Ｈ）−オン、７−
メチル−１−（３−メチルブチル）−１，８−ナフチリ
ジン−２（１Ｈ）−オン、５，６−ジメチル−１−（３
−メチルブチル）−１，８−ナフチリジン−２（１Ｈ）
−オン、1-Ethyl-6-methyl-1,8-naphthyridin-2 (1H) -one, 1-ethyl-7-methyl-
1,8-naphthyridine-2 (1H) -one, 1-ethyl-5,6-dimethyl-1,8-naphthyridine-2 (1
H) -one, 1-ethyl-5,7-dimethyl-1,8-
Naphthyridin-2 (1H) -one, 1-ethyl-6,7
-Dimethyl-1,8-naphthyridin-2 (1H) -one, 1-ethyl-5,6,7-trimethyl-1,8-naphthyridin-2 (1H) -one, 5-methyl-1-propyl-1. , 8-naphthyridine-2 (1H) -one, 6-
Methyl-1-propyl-1,8-naphthyridine-2 (1
H) -one, 7-methyl-1-propyl-1,8-naphthyridin-2 (1H) -one, 5,6-dimethyl-1-
Propyl-1,8-naphthyridine-2 (1H) -one,
5,7-Dimethyl-1-propyl-1,8-naphthyridin-2 (1H) -one, 6,7-dimethyl-1-propyl-1,8-naphthyridin-2 (1H) -one, 5,
6,7-Trimethyl-1-propyl-1,8-naphthyridin-2 (1H) -one, 1-isopropyl-5-methyl-1,8-naphthyridin-2 (1H) -one, 1-isopropyl-6- Methyl-1,8-naphthyridine-2
(1H) -one, 1-isopropyl-7-methyl-1,
8-naphthyridine-2 (1H) -one, 1-isopropyl-5,6-dimethyl-1,8-naphthyridine-2 (1
H) -one, 1-isopropyl-5,7-dimethyl-
1,8-naphthyridine-2 (1H) -one, 1-isopropyl-6,7-dimethyl-1,8-naphthyridine-2
(1H) -one, 1-isopropyl-5,6,7-trimethyl-1,8-naphthyridin-2 (1H) -one, 1
-Butyl-5-methyl-1,8-naphthyridine-2 (1
H) -one, 1-butyl-6-methyl-1,8-naphthyridin-2 (1H) -one, 1-butyl-7-methyl-
1,8-naphthyridine-2 (1H) -one, 1-butyl-5,6-dimethyl-1,8-naphthyridine-2 (1
H) -one, 1-butyl-5,7-dimethyl-1,8-
Naphthyridin-2 (1H) -one, 1-butyl-6,7
-Dimethyl-1,8-naphthyridin-2 (1H) -one, 1-butyl-5,6,7-trimethyl-1,8-naphthyridin-2 (1H) -one, 1-isobutyl-5-
Methyl-1,8-naphthyridin-2 (1H) -one, 1
-Isobutyl-6-methyl-1,8-naphthyridine-2
(1H) -one, 1-isobutyl-7-methyl-1,8
-Naphthyridin-2 (1H) -one, 1-isobutyl-
5,6-Dimethyl-1,8-naphthyridine-2 (1H)
-One, 1-isobutyl-5,7-dimethyl-1,8-
Naphthyridin-2 (1H) -one, 1-isobutyl-
6,7-Dimethyl-1,8-naphthyridine-2 (1H)
-One, 1-isobutyl-5,6,7-trimethyl-
1,8-Naphthyridin-2 (1H) -one, 5-methyl-1- (3-methylbutyl) -1,8-naphthyridine-
2 (1H) -one, 6-methyl-1- (3-methylbutyl) -1,8-naphthyridin-2 (1H) -one, 7-
Methyl-1- (3-methylbutyl) -1,8-naphthyridin-2 (1H) -one, 5,6-dimethyl-1- (3
-Methylbutyl) -1,8-naphthyridine-2 (1H)
-On,
【００１１】５，７−ジメチル−１−（３−メチルブチ
ル）−１，８−ナフチリジン−２（１Ｈ）−オン、６，
７−ジメチル−１−（３−メチルブチル）−１，８−ナ
フチリジン−２（１Ｈ）−オン、５，６，７−トリメチ
ル−１−（３−メチルブチル）−１，８−ナフチリジン
−２（１Ｈ）−オン、５−メチル−１−ペンチル−１，
８−ナフチリジン−２（１Ｈ）−オン、６−メチル−１
−ペンチル−１，８−ナフチリジン−２（１Ｈ）−オ
ン、７−メチル−１−ペンチル−１，８−ナフチリジン
−２（１Ｈ）−オン、５，６−ジメチル−１−ペンチル
−１，８−ナフチリジン−２（１Ｈ）−オン、５，７−
ジメチル−１−ペンチル−１，８−ナフチリジン−２
（１Ｈ）−オン、６，７−ジメチル−１−ペンチル−
１，８−ナフチリジン−２（１Ｈ）−オン、５，６，７
−トリメチル−１−ペンチル−１，８−ナフチリジン−
２（１Ｈ）−オン、１−ヘキシル−５−メチル−１，８
−ナフチリジン−２（１Ｈ）−オン、１−ヘキシル−６
−メチル−１，８−ナフチリジン−２（１Ｈ）−オン、
１−ヘキシル−７−メチル−１，８−ナフチリジン−２
（１Ｈ）−オン、１−ヘキシル−５，６−ジメチル−
１，８−ナフチリジン−２（１Ｈ）−オン、１−ヘキシ
ル−５，７−ジメチル−１，８−ナフチリジン−２（１
Ｈ）−オン、１−ヘキシル−６，７−ジメチル−１，８
−ナフチリジン−２（１Ｈ）−オン、１−ヘキシル−
５，６，７−トリメチル−１，８−ナフチリジン−２
（１Ｈ）−オン、５−メチル−１−（２−プロペニル）
−１，８−ナフチリジン−２（１Ｈ）−オン、６−メチ
ル−１−（２−プロペニル）−１，８−ナフチリジン−
２（１Ｈ）−オン、７−メチル−１−（２−プロペニ
ル）−１，８−ナフチリジン−２（１Ｈ）−オン、５，
６−ジメチル−１−（２−プロペニル）−１，８−ナフ
チリジン−２（１Ｈ）−オン、５，７−ジメチル−１−
（２−プロペニル）−１，８−ナフチリジン−２（１
Ｈ）−オン、６，７−ジメチル−１−（２−プロペニ
ル）−１，８−ナフチリジン−２（１Ｈ）−オン、５，
６，７−トリメチル−１−（２−プロペニル）−１，８
−ナフチリジン−２（１Ｈ）−オン、１−（３−ブテニ
ル）−５−メチル−１，８−ナフチリジン−２（１Ｈ）
−オン、１−（３−ブテニル）−６−メチル−１，８−
ナフチリジン−２（１Ｈ）−オン、１−（３−ブテニ
ル）−７−メチル−１，８−ナフチリジン−２（１Ｈ）
−オン、１−（３−ブテニル）−５，６−ジメチル−
１，８−ナフチリジン−２（１Ｈ）−オン、１−（３−
ブテニル）−５，７−ジメチル−１，８−ナフチリジン
−２（１Ｈ）−オン、１−（３−ブテニル）−６，７−
ジメチル−１，８−ナフチリジン−２（１Ｈ）−オン、
１−（３−ブテニル）−５，６，７−トリメチル−１，
８−ナフチリジン−２（１Ｈ）−オン、５−メチル−１
−（２−ペンテニル）−１，８−ナフチリジン−２（１
Ｈ）−オン、６−メチル−１−（２−ペンテニル）−
１，８−ナフチリジン−２（１Ｈ）−オン、７−メチル
−１−（２−ペンテニル）−１，８−ナフチリジン−２
（１Ｈ）−オン、５，６−ジメチル−１−（２−ペンテ
ニル）−１，８−ナフチリジン−２（１Ｈ）−オン、5,7-Dimethyl-1- (3-methylbutyl) -1,8-naphthyridin-2 (1H) -one, 6,
7-Dimethyl-1- (3-methylbutyl) -1,8-naphthyridine-2 (1H) -one, 5,6,7-trimethyl-1- (3-methylbutyl) -1,8-naphthyridine-2 (1H ) -One, 5-methyl-1-pentyl-1,
8-naphthyridine-2 (1H) -one, 6-methyl-1
-Pentyl-1,8-naphthyridin-2 (1H) -one, 7-methyl-1-pentyl-1,8-naphthyridin-2 (1H) -one, 5,6-dimethyl-1-pentyl-1,8 -Naphthyridin-2 (1H) -one, 5,7-
Dimethyl-1-pentyl-1,8-naphthyridine-2
(1H) -one, 6,7-dimethyl-1-pentyl-
1,8-naphthyridine-2 (1H) -one, 5,6,7
-Trimethyl-1-pentyl-1,8-naphthyridine-
2 (1H) -one, 1-hexyl-5-methyl-1,8
-Naphthyridin-2 (1H) -one, 1-hexyl-6
-Methyl-1,8-naphthyridin-2 (1H) -one,
1-hexyl-7-methyl-1,8-naphthyridine-2
(1H) -one, 1-hexyl-5,6-dimethyl-
1,8-naphthyridin-2 (1H) -one, 1-hexyl-5,7-dimethyl-1,8-naphthyridin-2 (1
H) -one, 1-hexyl-6,7-dimethyl-1,8
-Naphthyridin-2 (1H) -one, 1-hexyl-
5,6,7-Trimethyl-1,8-naphthyridine-2
(1H) -one, 5-methyl-1- (2-propenyl)
-1,8-naphthyridine-2 (1H) -one, 6-methyl-1- (2-propenyl) -1,8-naphthyridine-
2 (1H) -one, 7-methyl-1- (2-propenyl) -1,8-naphthyridin-2 (1H) -one, 5,
6-Dimethyl-1- (2-propenyl) -1,8-naphthyridin-2 (1H) -one, 5,7-dimethyl-1-
(2-propenyl) -1,8-naphthyridine-2 (1
H) -one, 6,7-dimethyl-1- (2-propenyl) -1,8-naphthyridin-2 (1H) -one, 5,
6,7-Trimethyl-1- (2-propenyl) -1,8
-Naphthyridine-2 (1H) -one, 1- (3-butenyl) -5-methyl-1,8-naphthyridine-2 (1H)
-One, 1- (3-butenyl) -6-methyl-1,8-
Naphthyridin-2 (1H) -one, 1- (3-butenyl) -7-methyl-1,8-naphthyridine-2 (1H)
-One, 1- (3-butenyl) -5,6-dimethyl-
1,8-naphthyridine-2 (1H) -one, 1- (3-
Butenyl) -5,7-dimethyl-1,8-naphthyridin-2 (1H) -one, 1- (3-butenyl) -6,7-
Dimethyl-1,8-naphthyridine-2 (1H) -one,
1- (3-butenyl) -5,6,7-trimethyl-1,
8-naphthyridine-2 (1H) -one, 5-methyl-1
-(2-Pentenyl) -1,8-naphthyridine-2 (1
H) -one, 6-methyl-1- (2-pentenyl)-
1,8-naphthyridine-2 (1H) -one, 7-methyl-1- (2-pentenyl) -1,8-naphthyridine-2
(1H) -one, 5,6-dimethyl-1- (2-pentenyl) -1,8-naphthyridine-2 (1H) -one,
【００１２】５，７−ジメチル−１−（２−ペンテニ
ル）−１，８−ナフチリジン−２（１Ｈ）−オン、６，
７−ジメチル−１−（２−ペンテニル）−１，８−ナフ
チリジン−２（１Ｈ）−オン、５，６，７−トリメチル
−１−（２−ペンテニル）−１，８−ナフチリジン−２
（１Ｈ）−オン、５−メチル−１−（４−ペンテニル）
−１，８−ナフチリジン−２（１Ｈ）−オン、６−メチ
ル−１−（４−ペンテニル）−１，８−ナフチリジン−
２（１Ｈ）−オン、７−メチル−１−（４−ペンテニ
ル）−１，８−ナフチリジン−２（１Ｈ）−オン、５，
６−ジメチル−１−（４−ペンテニル）−１，８−ナフ
チリジン−２（１Ｈ）−オン、５，７−ジメチル−１−
（４−ペンテニル）−１，８−ナフチリジン−２（１
Ｈ）−オン、5,7-Dimethyl-1- (2-pentenyl) -1,8-naphthyridin-2 (1H) -one, 6,
7-Dimethyl-1- (2-pentenyl) -1,8-naphthyridine-2 (1H) -one, 5,6,7-trimethyl-1- (2-pentenyl) -1,8-naphthyridine-2
(1H) -one, 5-methyl-1- (4-pentenyl)
-1,8-naphthyridine-2 (1H) -one, 6-methyl-1- (4-pentenyl) -1,8-naphthyridine-
2 (1H) -one, 7-methyl-1- (4-pentenyl) -1,8-naphthyridin-2 (1H) -one, 5,
6-Dimethyl-1- (4-pentenyl) -1,8-naphthyridin-2 (1H) -one, 5,7-dimethyl-1-
(4-Pentenyl) -1,8-naphthyridine-2 (1
H) -on,
【００１３】６，７−ジメチル−１−（４−ペンテニ
ル）−１，８−ナフチリジン−２（１Ｈ）−オン、５，
６，７−トリメチル−１−（４−ペンテニル）−１，８
−ナフチリジン−２（１Ｈ）−オン、１−（３−ヘキセ
ニル）−５−メチル−１，８−ナフチリジン−２（１
Ｈ）−オン、１−（３−ヘキセニル）−６−メチル−
１，８−ナフチリジン−２（１Ｈ）−オン、１−（３−
ヘキセニル）−７−メチル−１，８−ナフチリジン−２
（１Ｈ）−オン、１−（３−ヘキセニル）−５，６−ジ
メチル−１，８−ナフチリジン−２（１Ｈ）−オン、１
−（３−ヘキセニル）−５，７−ジメチル−１，８−ナ
フチリジン−２（１Ｈ）−オン、１−（３−ヘキセニ
ル）−６，７−ジメチル−１，８−ナフチリジン−２
（１Ｈ）−オン、１−（３−ヘキセニル）−５，６，７
−トリメチル−１，８−ナフチリジン−２6,7-Dimethyl-1- (4-pentenyl) -1,8-naphthyridin-2 (1H) -one, 5,
6,7-Trimethyl-1- (4-pentenyl) -1,8
-Naphthyridine-2 (1H) -one, 1- (3-hexenyl) -5-methyl-1,8-naphthyridine-2 (1
H) -one, 1- (3-hexenyl) -6-methyl-
1,8-naphthyridine-2 (1H) -one, 1- (3-
Hexenyl) -7-methyl-1,8-naphthyridine-2
(1H) -one, 1- (3-hexenyl) -5,6-dimethyl-1,8-naphthyridin-2 (1H) -one, 1
-(3-hexenyl) -5,7-dimethyl-1,8-naphthyridine-2 (1H) -one, 1- (3-hexenyl) -6,7-dimethyl-1,8-naphthyridine-2
(1H) -one, 1- (3-hexenyl) -5,6,7
-Trimethyl-1,8-naphthyridine-2
【００１４】（１Ｈ）−オン、１−ベンジル−５−メチ
ル−１，８−ナフチリジン−２（１Ｈ）−オン、１−ベ
ンジル−６−メチル−１，８−ナフチリジン−２（１
Ｈ）−オン、１−ベンジル−７−メチル−１，８−ナフ
チリジン−２（１Ｈ）−オン、１−ベンジル−５，６−
ジメチル−１，８−ナフチリジン−２（１Ｈ）−オン、
１−ベンジル−５，７−ジメチル−１，８−ナフチリジ
ン−２（１Ｈ）−オン、１−ベンジル−６，７−ジメチ
ル−１，８−ナフチリジン−２（１Ｈ）−オン、１−ベ
ンジル−５，６，７−トリメチル−１，８−ナフチリジ
ン−２（１Ｈ）−オン、５−メチル−１−フェネチル−
１，８−ナフチリジン−２（１Ｈ）−オン、(1H) -one, 1-benzyl-5-methyl-1,8-naphthyridine-2 (1H) -one, 1-benzyl-6-methyl-1,8-naphthyridine-2 (1
H) -one, 1-benzyl-7-methyl-1,8-naphthyridin-2 (1H) -one, 1-benzyl-5,6-
Dimethyl-1,8-naphthyridine-2 (1H) -one,
1-benzyl-5,7-dimethyl-1,8-naphthyridin-2 (1H) -one, 1-benzyl-6,7-dimethyl-1,8-naphthyridin-2 (1H) -one, 1-benzyl- 5,6,7-Trimethyl-1,8-naphthyridin-2 (1H) -one, 5-methyl-1-phenethyl-
1,8-naphthyridine-2 (1H) -one,
【００１５】６−メチル−１−フェネチル−１，８−ナ
フチリジン−２（１Ｈ）−オン、７−メチル−１−フェ
ネチル−１，８−ナフチリジン−２（１Ｈ）−オン、
５，６−ジメチル−１−フェネチル−１，８−ナフチリ
ジン−２（１Ｈ）−オン、５，７−ジメチル−１−フェ
ネチル−１，８−ナフチリジン−２（１Ｈ）−オン、
６，７−ジメチル−１−フェネチル−１，８−ナフチリ
ジン−２（１Ｈ）−オン、５，６，７−トリメチル−１
−フェネチル−１，８−ナフチリジン−２（１Ｈ）−オ
ン6-methyl-1-phenethyl-1,8-naphthyridin-2 (1H) -one, 7-methyl-1-phenethyl-1,8-naphthyridin-2 (1H) -one,
5,6-dimethyl-1-phenethyl-1,8-naphthyridin-2 (1H) -one, 5,7-dimethyl-1-phenethyl-1,8-naphthyridin-2 (1H) -one,
6,7-Dimethyl-1-phenethyl-1,8-naphthyridin-2 (1H) -one, 5,6,7-trimethyl-1
-Phenethyl-1,8-naphthyridine-2 (1H) -one
【００１６】上記本発明の化合物の製造方法は種々考え
られるが、代表的な製造法について以下に説明する。Various methods for producing the above-mentioned compound of the present invention are conceivable. Typical production methods will be described below.
【００１７】一般式（II)General formula (II)
【化４】
（式中、Ｒ2 〜Ｒ4 は、請求項１に定義したものと同じ
意味をもつ。）で表される化合物と、[Chemical 4] (Wherein R 2 to R 4 have the same meanings as defined in claim 1),
【００１８】一般式（III)General formula (III)
【化５】
（式中、Ｒ1 は請求項１に定義したものと同じ意味であ
り、Ｙは塩素, 臭素, ヨウ素等のハロゲン原子を示
す。）で表される化合物を、塩基性条件下にて反応させ
ることにより製造することができる。[Chemical 5] (Wherein R 1 has the same meaning as defined in claim 1 and Y represents a halogen atom such as chlorine, bromine or iodine.) Is reacted under a basic condition. It can be manufactured.
【００１９】上記の塩基性条件下の塩基とは、水素化ナ
トリウム等のアルカリ金属水素化物，水素化カルシウム
等のアルカリ土類金属水素化物、水酸化ナトリウム，水
酸化カリウム等のアルカリ金属水酸化物、炭酸ナトリウ
ム，炭酸カリウム等のアルカリ金属炭酸塩、炭酸水素ナ
トリウム，炭酸水素カリウム等のアルカリ金属炭酸水素
塩、ナトリウムメトキシド，ナトリウムエトキシド等の
アルカリ金属アルコキシド、トリエチルアミン等のトリ
アルキルアミン、ピリジン，４−ジメチルアミノピリジ
ン等のピリジン化合物などが挙げられる。The base under the above basic conditions means an alkali metal hydride such as sodium hydride, an alkaline earth metal hydride such as calcium hydride, and an alkali metal hydroxide such as sodium hydroxide and potassium hydroxide. , Alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, alkali metal alkoxides such as sodium methoxide and sodium ethoxide, trialkylamines such as triethylamine, pyridine, Examples thereof include pyridine compounds such as 4-dimethylaminopyridine.
【００２０】上記の反応は通常種々の溶媒、例えばジク
ロロメタン，メタノール，エタノール，ピリジン，Ｎ，
Ｎ−ジメチルホルムアミド，テトラヒドロフラン等のよ
うな反応に悪影響を及ぼさない慣用の溶媒、特に塩基が
アルカリ金属水酸化物，アルカリ金属炭酸塩，アルカリ
金属炭酸水素塩のときは、アルコールと水の混合物中で
行われる。The above reaction is usually carried out in various solvents such as dichloromethane, methanol, ethanol, pyridine, N,
A conventional solvent such as N-dimethylformamide, tetrahydrofuran, etc., which does not adversely affect the reaction, particularly when the base is an alkali metal hydroxide, an alkali metal carbonate or an alkali metal hydrogen carbonate, in a mixture of alcohol and water. Done.
【００２１】なお、反応温度は特に限定されないが、通
常は冷却下から加温下の範囲で反応が行われる。例えば
塩基として水酸化ナトリウムを用いた場合、反応温度は
０℃〜１００℃が好ましい。The reaction temperature is not particularly limited, but usually the reaction is carried out in the range of cooling to heating. For example, when sodium hydroxide is used as the base, the reaction temperature is preferably 0 ° C to 100 ° C.
【００２２】上記反応に用いる一般式（II）で表される
化合物は公知の物質であるか、または公知の方法を準用
することにより製造できる。（例えばジャーナル オブ
オルガニック ケミストリー、５５巻、４７４４〜４
７５０頁（１９９０））。The compound represented by the general formula (II) used in the above reaction is a known substance, or can be produced by applying a known method. (For example, Journal of Organic Chemistry, Volume 55, 4744-4
750 (1990)).
【００２３】前述した製造法で得られる本発明の化合物
は、例えば抽出，沈澱，分画クロマトグラフィー，分
別，結晶化，再結晶等の常法により単離，精製すること
ができる。The compound of the present invention obtained by the above-mentioned production method can be isolated and purified by a conventional method such as extraction, precipitation, fractionation chromatography, fractionation, crystallization and recrystallization.
【００２４】このようにして製造された本発明の化合物
は所望に応じて常法により医薬として許容される塩類、
例えば塩酸，臭化水素酸，硫酸，リン酸などの鉱酸との
塩；ギ酸，酢酸，フマル酸，マレイン酸，クエン酸など
の有機カルボン酸との塩；メタンスルホン酸，ベンゼン
スルホン酸，トルエンスルホン酸などのスルホン酸との
塩等に変化させることができる。The compound of the present invention thus produced is, if desired, a pharmaceutically acceptable salt,
For example, salts with mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid; salts with organic carboxylic acids such as formic acid, acetic acid, fumaric acid, maleic acid, citric acid; methanesulfonic acid, benzenesulfonic acid, toluene It can be changed to a salt with sulfonic acid such as sulfonic acid.
【００２５】次に、本発明の化合物の胃酸分泌抑制作
用，胃粘膜保護作用，抗潰瘍作用について説明するが、
ここに例示しない化合物についても同様の効果が認めら
れた。なお、結果を示す表中に用いた化合物番号は、後
述する実施例番号である。Next, the gastric acid secretion inhibitory action, gastric mucosa protective action and antiulcer action of the compound of the present invention will be explained.
Similar effects were observed with compounds not illustrated here. The compound numbers used in the tables showing the results are the example numbers described later.
【００２６】幽門結紮ラットモデル
試験方法
６〜７週令の雄性ＳＤ系ラットを４８時間絶食飼育し、
実験当日の早朝からはさらに絶水した。体重が各群で平
均化するように群分けし、１群６〜８匹とした。ラット
をエ−テルで軽麻酔後、腹部の毛を刈り剣状突起の１ｃ
ｍ下部で切開した。胃を体外へ引き出し、幽門と十二指
腸の結合部を絹糸で結紮した。被験薬物は十二指腸内へ
投与し、腹筋，腹部の皮膚を縫合後、ラットをケージに
戻して絶食絶水下で５時間放置した。Pylori ligation rat model test method Male SD rats of 6 to 7 weeks of age were fasted for 48 hours,
From the early morning on the day of the experiment, the water was further cut off. The animals were divided into groups so that the body weight was averaged in each group, and each group had 6 to 8 animals. After lightly anesthetizing the rat with ether, the hair of the abdomen was shaved and the xiphoid process 1c
An incision was made at the bottom of m. The stomach was pulled out of the body, and the junction between the pylorus and the duodenum was ligated with silk thread. The test drug was administered into the duodenum, the abdominal muscle and the skin of the abdomen were sutured, and the rat was returned to the cage and left under fasting and dewatering for 5 hours.
【００２７】５時間後、ラットをエーテル麻酔致死させ
て胃を摘出後、前胃部に小孔をあけ、胃液を試験管に採
取した。胃液は直ちに遠心分離して固形物を取り除き、
上清についてその総酸度（胃液０．５ｍｌに精製水７．
５ｍｌを加えたものを０．０１Ｎ水酸化ナトリウム溶液
にて中和滴定し、１ｍｌあたりの酸度に５時間で分泌し
た胃液量（目盛り付きスピッツグラスにて計測（ｍｌ／
５ｈｒ）を積算した。）を求めた。After 5 hours, the rat was killed by anesthetizing with ether and the stomach was excised. A small hole was made in the forestomach and a gastric juice was collected in a test tube. The gastric juice is immediately centrifuged to remove solids,
The total acidity of the supernatant (0.5 ml of gastric juice to purified water 7.
The amount of 5 ml added was neutralized and titrated with 0.01 N sodium hydroxide solution, and the amount of gastric juice secreted per 1 ml of acidity in 5 hours (measured with a graduated Spitz glass (ml /
5 hr) was integrated. ) Was asked.
【００２８】結果
得られた結果を第１表に示す。なお、表中の百分率は対
照群に対する各測定項目の増域百分率を示す。Results The results obtained are shown in Table 1. The percentages in the table indicate the percentage increase of each measurement item with respect to the control group.
【００２９】[0029]
【表１】 [Table 1]
【００３０】塩酸・エタノ−ル胃粘膜損傷モデル
試験方法
２４時間絶食した雄性ＳＤ系ラット（Ｂ．Ｗ．１８０〜
２１０ｇ）に被験薬物を経口投与し、その１時間後に１
５０ｍＭ塩酸を含む６０％エタノール液を５ｍｌ／ｋｇ
の用量で経口投与した。さらに、その１時間後にラット
をエーテル麻酔致死させて胃を摘出し、ホルマリン固定
後胃粘膜の損傷部の面積を画像解析装置を用いて計測し
た。Hydrochloric / Ethanol Gastric Mucosal Damage Model Test Method Male SD rats (BW 180-
210 g) was orally administered with the test drug, and 1 hour after that, 1
5 ml / kg of 60% ethanol solution containing 50 mM hydrochloric acid
Orally. Further, 1 hour after that, the rat was killed by ether anesthesia, the stomach was removed, and after fixing with formalin, the area of the damaged part of the gastric mucosa was measured using an image analyzer.
【００３１】結果
得られた結果を第２表に示す。なお、表中の百分率は対
照群に対する各測定項目の増域百分率を示す。Results The results obtained are shown in Table 2. The percentages in the table indicate the percentage increase of each measurement item with respect to the control group.
【００３２】[0032]
【表２】 [Table 2]
【００３３】急性毒性試験
次に、本発明の化合物の急性毒性を下記試験により確認
した。本発明の化合物（実施例番号２）を５週令のＩＣ
Ｒ雄性マウスに、３００ｍｇ／ｋｇ単回投与し、５日間
観察した結果死亡例は見られなかった。Acute toxicity test Next, the acute toxicity of the compound of the present invention was confirmed by the following test. The compound of the present invention (Example No. 2) was treated with IC at 5 weeks of age.
R male mice were administered with a single dose of 300 mg / kg and observed for 5 days. As a result, no death was observed.
【００３４】安定性試験
次に、本発明化合物の安定性を下記試験により確認し
た。本発明の化合物（実施例番号４）の結晶１０ｍｇを
試験管にとり、温度４０℃、相対湿度７５％の条件で８
０時間放置した。この検体をメタノールに溶解し、薄層
クロマトグラフィー（シリカゲル）に付し、塩化メチレ
ン対メタノール＝９対１の溶媒で展開した。本発明の化
合物は、試験前と後では、変化を認めなかった。この結
果から、本発明の化合物は非常に安定であることが判っ
た。Stability Test Next, the stability of the compound of the present invention was confirmed by the following test. 10 mg of a crystal of the compound of the present invention (Example No. 4) was placed in a test tube and heated under the conditions of a temperature of 40 ° C. and a relative humidity of 75%.
It was left for 0 hours. This sample was dissolved in methanol, subjected to thin layer chromatography (silica gel), and developed with a solvent of methylene chloride: methanol = 9: 1. The compound of the present invention showed no change before and after the test. From this result, it was found that the compound of the present invention is very stable.
【００３５】本発明の化合物は、このように胃酸分泌抑
制作用と胃粘膜保護作用を同時に併せ持ち、有効な抗潰
瘍作用を示すと共に安全かつ安定である。したがって、
本発明化合物は、胃潰瘍，十二指腸潰瘍，胃炎，ゾーリ
ンガーエリソン症候群などの予防ならびに治療に有効で
ある。As described above, the compound of the present invention has both gastric acid secretion inhibitory action and gastric mucosal protective action at the same time, exhibits an effective anti-ulcer action, and is safe and stable. Therefore,
The compound of the present invention is effective for the prevention and treatment of gastric ulcer, duodenal ulcer, gastritis, Solinger-Ellison syndrome and the like.
【００３６】本発明の化合物を上記の疾患の治療あるい
は予防を目的として投与する場合、散剤，顆粒剤，カプ
セル剤，シロップ剤などとして経口的に投与しても良い
し、また坐剤，注射剤，外用剤，点滴剤などとして非経
口的に投与しても良い。投与量は症状の程度，患者の年
齢，潰瘍の種類，既往歴などによって著しく異なるが、
通常は成人一日あたり約０．０１〜２００ｍｇ／ｋｇ、
好ましくは０．０５〜５０ｍｇ／ｋｇ、より好ましくは
０．１〜１０ｍｇ／ｋｇの割合で、一日１〜数回に分け
て投与する。When the compound of the present invention is administered for the purpose of treating or preventing the above-mentioned diseases, it may be orally administered as a powder, granules, capsules, syrup, etc., or as a suppository or injection. , May be parenterally administered as an external preparation or drip. The dose varies significantly depending on the severity of symptoms, patient age, ulcer type, medical history, etc.
Usually about 0.01 to 200 mg / kg per day for adults,
The dose is preferably 0.05 to 50 mg / kg, more preferably 0.1 to 10 mg / kg, and administered once to several times a day.
【００３７】製剤化の際は、通常の製剤担体を用い、当
該技術分野における常法にしたがって製造できる。即
ち、経口的固形製剤を製造する場合は、主薬に賦形剤及
び必要に応じて結合剤，崩壊剤，滑沢剤，着色剤，矯味
剤，矯臭剤などを加えた後、常法に従って錠剤，被覆製
剤，顆粒剤，散剤，カプセル剤などとする。賦形剤とし
ては、例えば乳糖，コーンスターチ，白糖，ブドウ糖，
ソルビット，結晶セルロース，二酸化ケイ素などが用い
られる。結合剤としては、例えばポリビニルアルコー
ル，ポリビニルエーテル，エチルセルロース，メチルセ
ルロース，アラビアゴム，トラガント，ゼラチン，シェ
ラック，ヒドロキシプロピルスターチ，ポリビニルピロ
リドンなどが用いられる。崩壊剤としては、例えば澱
粉，寒天，ゼラチン末，結晶セルロース，炭酸カルシウ
ム，炭酸水素ナトリウム，クエン酸カルシウム，デキス
トリン，ペクチンなどが用いられる。滑沢剤としては、
例えば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，硬化植物油などが用いられる。
着色剤としては、医薬品への添加が許可されているもの
が用いられる。矯味，矯臭剤としては、例えばココア
末，ハッカ脳，芳香酸，ハッカ油，龍脳，桂皮末などが
用いられる。In the case of formulation, it can be produced according to a conventional method in the art using a usual formulation carrier. That is, in the case of producing an oral solid preparation, an excipient and, if necessary, a binder, a disintegrating agent, a lubricant, a coloring agent, a flavoring agent, a flavoring agent, etc. are added to the main drug, and then the tablet is prepared according to a conventional method. , Coated preparations, granules, powders, capsules, etc. Examples of excipients include lactose, corn starch, sucrose, glucose,
Solbit, crystalline cellulose, silicon dioxide, etc. are used. As the binder, for example, polyvinyl alcohol, polyvinyl ether, ethyl cellulose, methyl cellulose, gum arabic, tragacanth, gelatin, shellac, hydroxypropyl starch, polyvinyl pyrrolidone, etc. are used. As the disintegrant, for example, starch, agar, powdered gelatin, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, calcium citrate, dextrin, pectin and the like are used. As a lubricant,
For example, magnesium stearate, talc, polyethylene glycol, silica, hydrogenated vegetable oil, etc. are used.
As the colorant, those permitted to be added to pharmaceuticals are used. As the corrigent and flavoring agent, for example, cocoa powder, mentha brain, aromatic acid, mint oil, Borneolum, cinnamon powder and the like are used.
【００３８】これらの錠剤，顆粒剤に糖衣，ゼラチン
衣、その他必要により適宜コーティングをほどこすこと
は、何ら差し支えない。注射剤を調製する場合には、必
要に応じて主薬にｐＨ調整剤，緩衝剤，安定化剤，可溶
化剤などを添加し、常法により皮下，筋肉内，静脈内用
注射剤とする。There is no problem in coating these tablets and granules with sugar coating, gelatin coating, and other coatings if necessary. When preparing an injection, a pH adjusting agent, a buffering agent, a stabilizer, a solubilizing agent, etc. are added to the main drug as necessary, and a subcutaneous, intramuscular or intravenous injection is prepared by a conventional method.
【００３９】[0039]
【実施例】次に、本発明をより詳細に説明するために実
施例を述べるが、本発明は何らこれらに限定されるもの
ではない。なお、実施例中の 1Ｈ−ＮＭＲ，13Ｃ−ＮＭ
Ｒ、ＭＳ（ＥＩ）はそれぞれプロトン核磁気共鳴スペク
トル、カーボン核磁気共鳴スペクトル、質量分析スペク
トル（ＥＩ法）を表わす。EXAMPLES Examples will now be described in order to explain the present invention in more detail, but the present invention is not limited to these. In addition, 1 H-NMR and 13 C-NM in the examples.
R and MS (EI) represent a proton nuclear magnetic resonance spectrum, a carbon nuclear magnetic resonance spectrum, and a mass spectrometry spectrum (EI method), respectively.
【００４０】実施例１
１，５−ジメチル−１，８−ナフチリジン−２（１Ｈ）
−オン
５−メチル−１，８−ナフチリジン−２（１Ｈ）−オン
0.４８ｇを水９ｍｌ、メタノール１５ｍｌに１ｇの水酸
化カリウムを溶かして調製した溶液１０ｍｌに加え、さ
らにヨウ化メチル0.６ｇを加え、室温にて６時間反応さ
せた後、メタノールを減圧下にて留去し、残渣をクロロ
ホルムにて３回抽出を行った。クロロホルム層を水で１
回、飽和食塩水１回洗浄した後、無水硫酸マグネシウム
で乾燥した。溶媒を留去して得られた残渣をシリカゲル
クロマトグラフィー（溶出溶媒はメタノール：クロロホ
ルム１：４９）で精製して１，５−ジメチル−１，８−
ナフチリジン−２（１Ｈ）−オンを0.４０ｇ得た。この
化合物の物性値を第３表に示す。Example 1 1,5-Dimethyl-1,8-naphthyridine-2 (1H)
5-one 5-methyl-1,8-naphthyridine-2 (1H) -one
0.48 g was added to 10 ml of a solution prepared by dissolving 1 g of potassium hydroxide in 9 ml of water and 15 ml of methanol, 0.6 g of methyl iodide was further added, and the mixture was reacted at room temperature for 6 hours, and then methanol was added under reduced pressure. The residue was extracted with chloroform three times. Chloroform layer with water 1
After washing once and saturated brine once, it was dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was purified by silica gel chromatography (eluent: methanol: chloroform 1:49) to give 1,5-dimethyl-1,8-.
0.40 g of naphthyridin-2 (1H) -one was obtained. The physical properties of this compound are shown in Table 3.
【００４１】実施例２
１，６−ジメチル−１，８−ナフチリジン−２（１Ｈ）
−オン
実施例１の５−メチル−１，８−ナフチリジン−２（１
Ｈ）−オンの代わりに６−メチル−１，８−ナフチリジ
ン−２（１Ｈ）−オン0.６４ｇを用い、同様の操作によ
り１，６−ジメチル−１，８−ナフチリジン−２（１
Ｈ）−オンを0.５１ｇ得た。この化合物の物性値を第３
表に示す。Example 2 1,6-Dimethyl-1,8-naphthyridine-2 (1H)
5-one of Example 1 5-methyl-1,8-naphthyridine-2 (1
Using 6-methyl-1,8-naphthyridin-2 (1H) -one (0.64 g) instead of (H) -one, 1,6-dimethyl-1,8-naphthyridin-2 (1
0.51 g of H) -one was obtained. The physical property value of this compound is
Shown in the table.
【００４２】実施例３
１，７−ジメチル−１，８−ナフチリジン−２（１Ｈ）
−オン
７−メチル−１，８−ナフチリジン−２（１Ｈ）−オン
0.８０ｇを水９ｍｌ、メタノール１５ｍｌに１ｇの水酸
化ナトリウムを溶かして調製した溶液１０ｍｌに加え、
さらにヨウ化メチル0.６ｇを加え、７０℃にて５時間反
応させた後、メタノールを減圧下にて留去し、残渣をク
ロロホルムにて３回抽出を行った。クロロホルム層を水
で１回、飽和食塩水１回洗浄した後、無水硫酸マグネシ
ウムで乾燥した。溶媒を留去して得られた残渣をシリカ
ゲルクロマトグラフィー（溶出溶媒はメタノール：クロ
ロホルム１：４９）で精製して１，７−ジメチル−１，
８−ナフチリジン−２（１Ｈ）−オンを０．６５ｇ得
た。この化合物の物性値を第３表に示す。Example 3 1,7-Dimethyl-1,8-naphthyridine-2 (1H)
-One 7-methyl-1,8-naphthyridine-2 (1H) -one
0.80 g was added to 10 ml of a solution prepared by dissolving 1 g of sodium hydroxide in 9 ml of water and 15 ml of methanol,
Further, 0.6 g of methyl iodide was added, and the mixture was reacted at 70 ° C. for 5 hours, then methanol was distilled off under reduced pressure, and the residue was extracted with chloroform three times. The chloroform layer was washed once with water and once with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel chromatography (eluent: methanol: chloroform 1:49) to give 1,7-dimethyl-1,
0.65 g of 8-naphthyridin-2 (1H) -one was obtained. The physical properties of this compound are shown in Table 3.
【００４３】実施例４
１，５，７−トリメチル−１，８−ナフチリジン−２
（１Ｈ）−オン
実施例３の７−メチル−１，８−ナフチリジン−２（１
Ｈ）−オンの代わりに５，７−ジメチル−１，８−ナフ
チリジン−２（１Ｈ）−オン１．１２ｇを用い、同様の
操作により１，５，７−トリメチル−１，８−ナフチリ
ジン−２（１Ｈ）−オンを０．９０ｇ得た。この化合物
の物性値を第３表に示す。Example 4 1,5,7-Trimethyl-1,8-naphthyridine-2
(1H) -one 7-methyl-1,8-naphthyridine-2 (1 of Example 3
1.12 g of 5,7-dimethyl-1,8-naphthyridine-2 (1H) -one was used instead of H) -one, and 1,5,7-trimethyl-1,8-naphthyridine-2 was obtained by the same operation. 0.90 g of (1H) -one was obtained. The physical properties of this compound are shown in Table 3.
【００４４】[0044]
【表３】 [Table 3]
【００４５】次に、本発明の処方例を示す。
実施例５
錠剤：実施例２の本発明の化合物０．５重量部及び乳糖
４．５重量部を混合粉砕し、この混合物に乳糖４８重量
部，結晶セルロース２２．５重量部及びステアリン酸マ
グネシウム０．４重量部を加えて均一に混合し、打錠機
を用いて加圧成形して７５ｍｇ／錠の錠剤とした。Next, a prescription example of the present invention will be shown. Example 5 Tablet: 0.5 part by weight of the compound of the present invention of Example 2 and 4.5 parts by weight of lactose were mixed and pulverized, and 48 parts by weight of lactose, 22.5 parts by weight of crystalline cellulose and magnesium stearate were mixed in this mixture. 0.4 parts by weight was added and mixed uniformly, and pressure-molded using a tableting machine to give tablets of 75 mg / tablet.
【００４６】実施例６
カプセル剤：実施例２の本発明の化合物０．５重量部及
び乳糖４．５重量部を混合粉砕し、この混合物に乳糖１
４．５重量部，トウモロコシデンプン６０．０重量部及
びステアリン酸マグネシウム２．０重量部を加えて均一
に混合し、これを１カプセルあたり２００ｍｇの割合で
３号ゼラチン硬カプセルに充填してカプセル剤とした。Example 6 Capsule: 0.5 part by weight of the compound of the present invention of Example 2 and 4.5 parts by weight of lactose were mixed and ground, and this mixture was mixed with lactose 1
4.5 parts by weight, 60.0 parts by weight of corn starch and 2.0 parts by weight of magnesium stearate were added and uniformly mixed, and 200 mg per capsule was filled in a No. 3 gelatin hard capsule to form a capsule. And
【００４７】[0047]
【発明の効果】本発明の化合物は文献未収載の新規化合
物であり、簡便な方法で製造することができる。この化
合物は抗潰瘍作用を有しており、しかも毒性が低いの
で、抗潰瘍剤として有用である。INDUSTRIAL APPLICABILITY The compound of the present invention is a novel compound which has not been published in the literature and can be produced by a simple method. This compound has an anti-ulcer effect and has low toxicity, and therefore is useful as an anti-ulcer agent.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 長谷 岳真 静岡県焼津市岡当目10番地 サツポロビー ル株式会社医薬開発研究所内 (72)発明者 栗原 利夫 静岡県焼津市岡当目10番地 サツポロビー ル株式会社医薬開発研究所内 (72)発明者 小林 富二男 静岡県焼津市岡当目10番地 サツポロビー ル株式会社医薬開発研究所内 (72)発明者 松浦 昭宏 静岡県焼津市岡当目10番地 サツポロビー ル株式会社医薬開発研究所内 (72)発明者 奥村 浩 静岡県焼津市岡当目10番地 サツポロビー ル株式会社医薬開発研究所内 (72)発明者 芦澤 直樹 静岡県焼津市岡当目10番地 サツポロビー ル株式会社医薬開発研究所内 ─────────────────────────────────────────────────── ─── Continued front page (72) Inventor Takemasa Hase Shizuoka Prefecture Yaizu City Oka Tome No. 10 Satsupo Lobby Le Pharmaceutical Co., Ltd. (72) Inventor Toshio Kurihara Shizuoka Prefecture Yaizu City Oka Tome No. 10 Satsupo Lobby Le Pharmaceutical Co., Ltd. (72) Inventor Tomio Kobayashi Shizuoka Prefecture Yaizu City Oka Tome No. 10 Satsupo Lobby Le Pharmaceutical Co., Ltd. (72) Inventor Akihiro Matsuura Shizuoka Prefecture Yaizu City Oka Tome No. 10 Satsupo Lobby Le Pharmaceutical Co., Ltd. (72) Inventor Hiroshi Okumura Shizuoka Prefecture Yaizu City Oka Tome No. 10 Satsupo Lobby Le Pharmaceutical Co., Ltd. (72) Inventor Naoki Ashizawa Shizuoka Prefecture Yaizu City Oka Tome No. 10 Satsupo Lobby Le Pharmaceutical Co., Ltd.
Claims (3)
ラルキル基を示す。Ｒ2 〜Ｒ4 は各々独立に水素原子ま
たは低級アルキル基，低級アルケニル基，アラルキル基
を示す。ただし、Ｒ2 〜Ｒ4 のすべてが同時に水素原子
ではありえない。）で表される新規な１，８−ナフチリ
ジン誘導体またはその医薬的に許容される塩。1. The following general formula (I): (In the formula, R 1 represents a lower alkyl group, a lower alkenyl group, an aralkyl group .R 2 to R 4 each independently represent a hydrogen atom or a lower alkyl group, lower alkenyl group, an aralkyl group. However, R 2 ~ A new 1,8-naphthyridine derivative represented by the formula ( 4 ) cannot be all hydrogen atoms at the same time, or a pharmaceutically acceptable salt thereof.
誘導体またはその医薬的に許容される塩を有効成分とし
て含有する抗潰瘍剤。2. An anti-ulcer agent containing the 1,8-naphthyridine derivative or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
味を持つ。）で表される化合物に、塩基の存在下、Ｒ1
に相当するハロゲン化物Ｒ1 Ｙ（式中、Ｒ1 は請求項１
に定義したものと同じ意味をもち、Ｙは塩素原子，臭素
原子またはヨウ素原子を示す。）を反応せしめることを
特徴とする請求項１に記載の１，８−ナフチリジン誘導
体の製造法。3. The following general formula (II): (Wherein R 2 to R 4 have the same meanings as defined in claim 1) and R 1 in the presence of a base.
Corresponding to R 1 Y (wherein R 1 is
Y has the same meaning as defined above, and Y represents a chlorine atom, a bromine atom or an iodine atom. ) Is reacted, The manufacturing method of the 1,8-naphthyridine derivative of Claim 1 characterized by the above-mentioned.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3202260A JPH0525172A (en) | 1991-07-18 | 1991-07-18 | 1,8-naphthyridine derivative, its production and antiulcer agent containing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3202260A JPH0525172A (en) | 1991-07-18 | 1991-07-18 | 1,8-naphthyridine derivative, its production and antiulcer agent containing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0525172A true JPH0525172A (en) | 1993-02-02 |
Family
ID=16454599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3202260A Pending JPH0525172A (en) | 1991-07-18 | 1991-07-18 | 1,8-naphthyridine derivative, its production and antiulcer agent containing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0525172A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0900789A2 (en) * | 1997-08-29 | 1999-03-10 | SSP Co., Ltd. | Substituted quinolone derivatives and pharmaceuticals containing the same |
-
1991
- 1991-07-18 JP JP3202260A patent/JPH0525172A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0900789A2 (en) * | 1997-08-29 | 1999-03-10 | SSP Co., Ltd. | Substituted quinolone derivatives and pharmaceuticals containing the same |
| EP0900789A3 (en) * | 1997-08-29 | 2000-02-02 | SSP Co., Ltd. | Substituted quinolone derivatives and pharmaceuticals containing the same |
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