JPH0459776A - Phenoxypropylamine derivative and antitulcer agent containing the same - Google Patents
Phenoxypropylamine derivative and antitulcer agent containing the sameInfo
- Publication number
- JPH0459776A JPH0459776A JP16663290A JP16663290A JPH0459776A JP H0459776 A JPH0459776 A JP H0459776A JP 16663290 A JP16663290 A JP 16663290A JP 16663290 A JP16663290 A JP 16663290A JP H0459776 A JPH0459776 A JP H0459776A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- ulcer
- present
- phenoxypropylamine
- compound
- 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.)
- Granted
Links
- DXVQSHRBALIFBC-UHFFFAOYSA-N 3-phenoxypropan-1-amine Chemical class NCCCOC1=CC=CC=C1 DXVQSHRBALIFBC-UHFFFAOYSA-N 0.000 title claims description 17
- 239000003699 antiulcer agent Substances 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims 2
- 208000025865 Ulcer Diseases 0.000 abstract description 13
- 231100000397 ulcer Toxicity 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 12
- 239000002904 solvent Substances 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 125000000446 sulfanediyl group Chemical group *S* 0.000 abstract description 6
- 230000001681 protective effect Effects 0.000 abstract description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 abstract description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 abstract description 3
- 239000012298 atmosphere Substances 0.000 abstract description 2
- 239000011261 inert gas Substances 0.000 abstract description 2
- 238000010992 reflux Methods 0.000 abstract description 2
- 239000000725 suspension Substances 0.000 abstract description 2
- 150000003573 thiols Chemical class 0.000 abstract description 2
- 210000004211 gastric acid Anatomy 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 230000000767 anti-ulcer Effects 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000004611 spectroscopical analysis Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- -1 1so-butyl Chemical group 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000027119 gastric acid secretion Effects 0.000 description 3
- ZLYRPVTXHARSPL-UHFFFAOYSA-N 1,3-dihydroimidazo[4,5-b]pyridine-2-thione Chemical compound C1=CC=C2NC(S)=NC2=N1 ZLYRPVTXHARSPL-UHFFFAOYSA-N 0.000 description 2
- XYOXIERJKILWCG-UHFFFAOYSA-N 4-chlorobutanamide Chemical compound NC(=O)CCCCl XYOXIERJKILWCG-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- SCARFFIFMQUARC-UHFFFAOYSA-N 1,3-dihydroimidazo[4,5-c]pyridine-2-thione Chemical compound C1=NC=C2NC(=S)NC2=C1 SCARFFIFMQUARC-UHFFFAOYSA-N 0.000 description 1
- VJIOSCMTZVXQQU-UHFFFAOYSA-N 2-chlorobutanamide Chemical compound CCC(Cl)C(N)=O VJIOSCMTZVXQQU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 206010042220 Stress ulcer Diseases 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MSZJEPVVQWJCIF-UHFFFAOYSA-N butylazanide Chemical compound CCCC[NH-] MSZJEPVVQWJCIF-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical class CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 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
- 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
- 229940124597 therapeutic agent Drugs 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
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (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、新規なフェノキシプロピルアミン誘導体およ
びこれを含有する抗潰瘍剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel phenoxypropylamine derivative and an antiulcer agent containing the same.
ヒスタミンＨ２拮抗剤の開発により潰瘍の治療は容易に
なったが投与中止後の再発が現在問題になっている。再
発は防御因子の低下によって起こると考えられることか
ら胃酸分泌抑制作用と防御因子増強作用を併せ持つ薬剤
の開発が望まれている。The development of histamine H2 antagonists has made it easier to treat ulcers, but recurrence after discontinuing administration is currently a problem. Since recurrence is thought to be caused by a decrease in protective factors, there is a desire to develop a drug that has both the effect of suppressing gastric acid secretion and the effect of enhancing protective factors.
本発明者らはフェノキシプロピルアミン誘導体を種々合
成しその生理作用を鋭意研究した結果、本発明に係るフ
ェノキシプロピルアミン誘導体が強力な胃酸分泌抑制作
用と防御因子増強作用を有することを見い出し本発明を
完成するに至った。As a result of synthesizing various phenoxypropylamine derivatives and intensively studying their physiological effects, the present inventors discovered that the phenoxypropylamine derivative according to the present invention has a strong gastric acid secretion suppressing effect and a protective factor enhancing effect. It was completed.
本発明のフェノキシプロピルアミン誘導体は潰瘍の治療
に有用である。The phenoxypropylamine derivatives of the present invention are useful in treating ulcers.
従って本発明は、フェノキシプロピルアミン誘導体体お
よびこれを含有する抗潰瘍剤を提供することを目的とす
る。Accordingly, an object of the present invention is to provide phenoxypropylamine derivatives and antiulcer agents containing the same.
ｃ課通を解決するための手段〕
上記目的に沿う本発明は式（１）
ジプロピルアミン誘導体またはその塩を含有する抗潰瘍
剤である。Means for Solving Problems with Section C] The present invention, which achieves the above object, is an anti-ulcer agent containing a dipropylamine derivative of formula (1) or a salt thereof.
ＲおよびＲ２における低級アルキル基の例としては、メ
チル、エチル、ｎ−プロピル、１ｓｏ−プロピル、ｎ−
ブチル、１ｓｏ−ブチル、ｔｅｒｔ−ブチルのような炭
素原子数１〜４の直鎖状または分枝鎖状のアルキル基が
あげられる。Examples of lower alkyl groups in R and R2 include methyl, ethyl, n-propyl, 1so-propyl, n-
Examples include linear or branched alkyl groups having 1 to 4 carbon atoms such as butyl, 1so-butyl, and tert-butyl.
本発明の前記式（１）で示されるフェノキシプロピルア
ミン誘導体は以下に示す方法によって製造される。The phenoxypropylamine derivative represented by the formula (1) of the present invention is produced by the method shown below.
式（ＩＩ）
−ＣＨ−Ｎ−または−Ｎ−ＣＨ−を有する基を示し、ｎ
は１乃至５の整数を示す。〕で表わされるフェノキシプ
ロピルアミン誘導体また番よその生理学的に許容し得る
塩である。Formula (II) represents a group having -CH-N- or -N-CH-, and n
represents an integer from 1 to 5. ] or other physiologically acceptable salts thereof.
また本発明は前記式（Ｉ）で示されるフェノキ〔式中、
Ｒ１，Ｒ２およびｎは前述したものと同一であり、Ｘは
ＣＩまたはＢｒを示す。〕を有する化合物と、式（ｍ）
〔式中、Ａは前述したものと同一である〕を有するチオ
ール誘導体とを塩基の存在下で反応させることにより得
られる。塩基としては水酸化ナトリウム、水酸化カリウ
ム、水素化ナトリウム、ナトリウムアルコラード、ｎ−
ブチルリチウムなど用いることができる。また溶媒とし
ては、テトラヒドロフラン、ジメチルホルムアミド、ジ
メチルスルフオキシド、エチルエーテルなどを用いるこ
とができる。反応は不活性ガスの雰囲気下で０℃から溶
媒の還流温度の範囲で約１〜２４時間行うことが望まし
い。反応終了後、所望の生成物は常法に従って反応混合
物中から採取される。例えば、反応混合物を水に注ぎ、
酢酸エチルのような適当な有機溶媒で抽出し、抽出液を
乾燥後、溶媒を留去し、残留物をシリカゲルクロマトグ
ラフィー処理すると、所望の生成物が得られる。The present invention also provides a fenoki tree represented by the formula (I) [wherein,
R1, R2 and n are the same as described above, and X represents CI or Br. ] and a thiol derivative having the formula (m) [wherein A is the same as described above] in the presence of a base. Bases include sodium hydroxide, potassium hydroxide, sodium hydride, sodium alcoholade, n-
Butyl lithium or the like can be used. Further, as the solvent, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, ethyl ether, etc. can be used. The reaction is preferably carried out in an inert gas atmosphere at a temperature ranging from 0° C. to the reflux temperature of the solvent for about 1 to 24 hours. After the reaction is complete, the desired product is recovered from the reaction mixture according to conventional methods. For example, pour the reaction mixture into water,
Extraction with a suitable organic solvent such as ethyl acetate, drying of the extract, evaporation of the solvent and chromatography of the residue on silica gel yields the desired product.
本発明のフェノキシプロピルアミン誘導体は抗潰瘍剤と
して使用され投与量は症状により異なるが一般に成人１
日量ｌＯ〜２０００■、好ましくは２０〜６００■であ
り、症状に応じて必要により１〜３回に分けて投与する
のがよい。投与方法は投与に適した任意の形態をとるこ
とができ、特に経口投与が望ましいが静注も可能である
。The phenoxypropylamine derivative of the present invention is used as an anti-ulcer agent, and the dosage varies depending on the symptoms, but it is generally used for adults.
The daily dose is 10 to 2,000 square meters, preferably 20 to 600 square meters, and is preferably administered in 1 to 3 doses depending on the symptoms. The administration method can take any form suitable for administration, and oral administration is particularly preferred, but intravenous injection is also possible.
本発明の化合物は有効成分若しくは有効成分の１つとし
て単独又は通常の方法で製剤担体あるいは賦形剤等と混
合され、錠剤、糖衣錠、散剤、カプセル剤、顆粒剤、懸
濁剤、乳剤、注射液等に製剤化された種々の形態で適用
できる。担体あるいは賦形剤の例としては炭酸カルシウ
ム、リン酸カルシウム、でんぷん、ブドウ糖、乳糖、デ
キストリン、アルギン酸、マンニトール、タルク、ステ
アリン酸マグネシウム等があげられる。The compound of the present invention can be used as an active ingredient or one of the active ingredients alone or mixed with a pharmaceutical carrier or excipient in a conventional manner, and can be used as a tablet, sugar-coated tablet, powder, capsule, granule, suspension, emulsion, or injection. It can be applied in various forms such as liquid formulations. Examples of carriers or excipients include calcium carbonate, calcium phosphate, starch, glucose, lactose, dextrin, alginic acid, mannitol, talc, magnesium stearate, and the like.
次に実施例および試験例を示して本発明をさらに具体的
に説明するが、本発明はこれらに何ら限定されるもので
はない。EXAMPLES Next, the present invention will be explained in more detail with reference to Examples and Test Examples, but the present invention is not limited thereto.
以下、本発明の実施例を図面を参照して具体的に説明す
る。Embodiments of the present invention will be specifically described below with reference to the drawings.
〈実施例１〉
アルゴン雰囲気下、水素化ナトリウム０．２４ｇをＮ、
Ｎ−ジメチルホルムアミド１０ｍ１に懸濁し氷冷下２−
メルカプトピリド（２，３−ｄ）イミダゾール０．９１
ｇを加え、３０分間撹拌した。これにＮ−Ｃ３−（３−
（ピペリジノメチル）フェノキシ）プロピル〕 −２−
クロロアセトアミド１．３１ｇをＮ、Ｎ−ジメチルホル
ムアミド１０ｍ１に溶解した溶液を加え、室温で１６時
間撹拌した。反応混合物を水にそそぎ酢酸エチルで抽出
した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウ
ムで乾燥した。溶媒を減圧下留去し、残渣をシリカゲル
カラムクロマトグラフィーに付し、クロロホルム−メタ
ノール（２０：１）溶出画分よりＮ−〔３（３−（ピペ
リジノメチル）フェノキシ）プロピル）−２−（２−（
ピリド［２，３−ｄ）イミダゾリル）チオ）アセトアミ
ド１．２０ｇを得た。このものの分光学的データは下記
式（■）の構造を支持する。<Example 1> Under an argon atmosphere, 0.24 g of sodium hydride was mixed with N,
Suspended in 10 ml of N-dimethylformamide and cooled on ice for 2-
Mercaptopyrido(2,3-d)imidazole 0.91
g and stirred for 30 minutes. To this, N-C3-(3-
(piperidinomethyl)phenoxy)propyl] -2-
A solution of 1.31 g of chloroacetamide dissolved in 10 ml of N,N-dimethylformamide was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography, and the fraction eluted with chloroform-methanol (20:1) was extracted with N-[3(3-(piperidinomethyl)phenoxy)propyl)-2-(2- (
1.20 g of pyrido[2,3-d)imidazolyl)thio)acetamide was obtained. Spectroscopic data of this product support the structure of the following formula (■).
ｎ ｍ ｒ （ＣＤ Ｃｆｌ ａ ）δ１．２〜２．７
（ｉ、１２Ｈ）、３．４７（ｓ、２Ｊ（）、ｓ、５ｏ（
ｔ、２）１．Ｊ−ａｌ（ｚ）、３．８０（ｔ 、 ２Ｂ
、 Ｊ ＝８Ｈｚ）、３．９３（ｓ、２Ｈ）、６．５
〜７．８（ｉ 、 ７Ｈ）、８．２７（ｄ、ＩＨ，Ｊ−
５Ｈ２）〈実施例２〉
アルゴン雰囲気下、水素化ナトリウム０．１７ｇをＮ、
Ｎ−ジメチルホルムアミド１０ｍ１に懸濁し、水冷下２
−メルカプトピリド（２，３−ｄ）イミダゾール０．８
４ｇを加え３０分間撹拌した。これにＮ−［３−（３−
（ピペリジノメチル）フェノキシ）プロピル〕 −４−
クロロブチルアミｔ’１．０ｏｓｒをＮ、Ｎ−ジメチル
ホルムアミド１０ｍ１に溶解した溶液を加え、室温で１
６時間撹拌した。反応混合物を水にそそぎ酢酸エチルで
抽出した。有機層を飽和食塩水で洗浄し無水硫酸ナトリ
ウムで乾燥した。溶媒を減圧下留去し残渣をシリカゲル
カラムクロマトグラフィーに付し、クロロホルム−メタ
ノール（２０：１）溶出画分よりＮ−（３−（３−（ピ
ペリジノメチル）フェノキシ）プロピル） 、 ４−１
２− （ピリド（２，３−ｄ）イミダゾリル）チオ）ブ
チルアミド０．６８ｇを得た。このものの分光学的デー
タは下記式（Ｖ）の構造を支持する。n m r (CD Cfl a ) δ1.2-2.7
(i, 12H), 3.47(s, 2J(), s, 5o(
t, 2) 1. J-al(z), 3.80(t, 2B
, J = 8Hz), 3.93(s, 2H), 6.5
~7.8 (i, 7H), 8.27 (d, IH, J-
5H2) <Example 2> Under an argon atmosphere, 0.17 g of sodium hydride was mixed with N,
Suspended in 10 ml of N-dimethylformamide and cooled with water for 2 hours.
-Mercaptopyrido(2,3-d)imidazole 0.8
4 g was added and stirred for 30 minutes. To this, N-[3-(3-
(piperidinomethyl)phenoxy)propyl] -4-
A solution of chlorobutyramide t'1.0osr dissolved in 10ml of N,N-dimethylformamide was added, and the mixture was heated to 1.0ml at room temperature.
Stirred for 6 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the residue was subjected to silica gel column chromatography, and the fraction eluted with chloroform-methanol (20:1) was extracted with N-(3-(3-(piperidinomethyl)phenoxy)propyl), 4-1.
0.68 g of 2-(pyrido(2,3-d)imidazolyl)thio)butyramide was obtained. Spectroscopic data of this product support the structure of formula (V) below.
ｎｍ ｒ （ＣＤＣ１ｌ ３）６１．２〜２．７（＋ａ
、１Ｉ３Ｈ）、３．１〜３．７（ｍ、８Ｈ）、 ３．９
３（ｔ、２Ｈ，Ｊ−６Ｈ２）、８．５〜７．８（ｍ、７
Ｈ）、８．２８（ｄ、ＩＨ，Ｊ−５Ｈｚ）〈実施例３〉
アルゴン雰囲気下、水素化ナトリウム０．２６ｇをＮ、
Ｎ−ジメチルホルムアミド２０ｍ１に懸濁し、水冷下２
−メルカプトピリド［２，３−ｄ）イミダゾ−Ｊｌ、０
．８８ｇを加え、２０分間撹拌した。これにＮ−（３−
（３−（ピペリジノメチル）フェノキシ）プロピル〕
−６−プロモヘキシルアミド２．２４．をＮ、Ｎ−ジメ
チルホルムアミド２０ｍ１に溶解した溶液を加え、室温
で１６時間撹拌した。反応混合物を水にそそぎ酢酸エチ
ルで抽出した。有機層を飽和食塩水で洗浄し無水硫酸ナ
トリウムで乾燥した。溶媒を減圧下留去し、残渣をシリ
カゲルカラムクロマトグラフィーに付しクロロホルム−
メタノール（２０：１）溶出画分よりＮ−［３−（３−
（ピペリジノメチル）フェノキシ）プロピル〕−６（２
−（ピリド（２，３−ｄ）イミダゾリル）チオ）へキシ
ルアミド１．８０ｇを得た。nm r (CDC1l 3)61.2~2.7(+a
, 1I3H), 3.1-3.7 (m, 8H), 3.9
3 (t, 2H, J-6H2), 8.5-7.8 (m, 7
H), 8.28 (d, IH, J-5Hz) <Example 3> Under an argon atmosphere, 0.26 g of sodium hydride was mixed with N,
Suspended in 20ml of N-dimethylformamide and cooled with water for 2 hours.
-Mercaptopyrido[2,3-d)imidazo-Jl,0
．． 88 g was added and stirred for 20 minutes. To this, N-(3-
(3-(piperidinomethyl)phenoxy)propyl]
-6-promohexylamide 2.24. A solution of N,N-dimethylformamide (20 ml) was added thereto, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography.
N-[3-(3-
(piperidinomethyl)phenoxy)propyl]-6(2
1.80 g of -(pyrido(2,3-d)imidazolyl)thio)hexylamide was obtained.
このものの分光学的データは下記式（Ｖｌ）の構造を支
持する。Spectroscopic data of this product support the structure of the following formula (Vl).
ｎ ｍ ｒ （ＣＤ ＣＲａ ）６１．２〜２．７（ｍ
、２０Ｂ）、３．１〜３．７（ｓ、８Ｈ）、３．８７（
ｔ、２）１．Ｊ−６Ｈｚ）、１３．５〜７．８（ｓ、７
Ｈ）、８．２３（ｄ、ＩＨ，Ｊ−５Ｈ２）〈実施例４〉
アルゴン雰囲気下、水素化ナトリウム０．２３ｇをＮ、
Ｎ−ジメチルホルムアミドｌｏｍｌに懸濁し氷冷下２−
メルカプトピリド［３，４−ｄ］イミダゾールｏ、ｇ’
ｙｇを加え２０分間撹拌した。これにＮ−（３（３−（
ピペリジノメチル）フェノキシ）プロピル〕 −４−ク
ロロブチルアミド１．８９ｇをＮ、Ｎ−ジメチルホルム
アミド１０ｍ１に溶解した溶液を加え室温で１６時間撹
拌した。反応混合物を水にそそぎ酢酸エチルで抽出した
。有機層を飽和食塩水で洗浄し無水硫酸ナトリウムで乾
燥した。溶媒を減圧下留去し残渣をシリカゲルカラムク
ロマトグラフィーに付しクロロホルム−メタノール（２
０：１）溶出画分より、Ｎ−（３−（３−（ピペリジノ
メチル）フェノキシ）プロピル）−４−（２−（ピリド
［３，４−ｄ］イミダゾリル）チオ）ブチルアミド１．
０２ｇを得た。n m r (CD CRa ) 61.2 to 2.7 (m
, 20B), 3.1-3.7 (s, 8H), 3.87 (
t, 2) 1. J-6Hz), 13.5-7.8(s, 7
H), 8.23 (d, IH, J-5H2) <Example 4> Under an argon atmosphere, 0.23 g of sodium hydride was mixed with N,
Suspended in N-dimethylformamide loml and cooled on ice for 2-
Mercaptopyrido[3,4-d]imidazole o, g'
yg was added and stirred for 20 minutes. To this, N-(3(3-(
A solution of 1.89 g of piperidinomethyl)phenoxy)propyl]-4-chlorobutyramide dissolved in 10 ml of N,N-dimethylformamide was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography using chloroform-methanol (2
0:1) From the elution fraction, N-(3-(3-(piperidinomethyl)phenoxy)propyl)-4-(2-(pyrido[3,4-d]imidazolyl)thio)butylamide 1.
02g was obtained.
このものの分光学的データは下記式（■）の構造を支持
する。Spectroscopic data of this product support the structure of the following formula (■).
ｎ ｍ ｒ （ＣＤ ＣＩ！ ｓ ）δ １．２〜２．
７（ｓ、１６Ｈ）、３．１〜３．７（＊、８）１）、
６．５〜７．７（ｍ、６Ｈ）、
８．７７（ｓ、ＩＨ）
３．９０（ｔ、２Ｈ，Ｊ−８）１ｚ）、８．２０（ｄ、
ＩＪ（、Ｊ−５）＋２）、〈実施例５〉
アルゴン雰囲気下、水素化ナトリウム０．２７ｇをＮ、
Ｎ−ジメチルホルムアミド１０ｍ１に懸濁し氷冷下２−
メルカプトピリド（２，３−ｄ）イミダゾール０．９２
ｇを加え、２０分間撹拌した。これにＮ−（３−＋３−
（ピロリジノメチル）フェノキシ）プロピル〕 −
４−クロロブチルアミド１．８５ｇをＮ、Ｎ−ジメチル
ホルムアミド１０ｍ１に溶解した溶液を加え、室温で１
６時間撹拌した。反応混合物を水にそそぎ酢酸エチルで
抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナト
リウムで乾燥した。n m r (CD CI! s ) δ 1.2-2.
7 (s, 16H), 3.1-3.7 (*, 8) 1), 6.5-7.7 (m, 6H), 8.77 (s, IH) 3.90 (t, 2H) , J-8) 1z), 8.20(d,
IJ(, J-5)+2), <Example 5> Under an argon atmosphere, 0.27 g of sodium hydride was mixed with N,
Suspended in 10 ml of N-dimethylformamide and cooled on ice for 2-
Mercaptopyrido(2,3-d)imidazole 0.92
g and stirred for 20 minutes. To this, N-(3-+3-
(pyrrolidinomethyl)phenoxy)propyl〕 −
A solution of 1.85 g of 4-chlorobutyramide dissolved in 10 ml of N,N-dimethylformamide was added, and 1.85 g of 4-chlorobutyramide was dissolved at room temperature.
Stirred for 6 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate.
溶媒を減圧下留去し残渣をシリカゲルカラムクロマトグ
ラフィーに付しクロロホルム−メタノール（２０：１）
溶出画分よりＮ−［３−＋３− （ピロリジノメチル
）フェノキシ）プロピル〕 −４−（２−（ピリド（２
，３−ｄ）イミダゾリル）チオ）ブチルアミド０．８９
ｇを得た。The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography using chloroform-methanol (20:1).
From the elution fraction, N-[3-+3-(pyrrolidinomethyl)phenoxy)propyl]-4-(2-(pyrido(2
, 3-d) imidazolyl)thio)butyramide 0.89
I got g.
このものの分光学的データは下記式（■）の構造を支持
する。Spectroscopic data of this product support the structure of the following formula (■).
ｎｍｒ （ＣＤＣＩ ３）δ １．２〜２．７（１，１
４Ｈ）、３．１〜３．８（ｓ、４Ｈ）、３．８０（Ｓ、
２Ｂ）、３，９０Ｃｔ、２Ｈ，Ｊ＝ＢＨｚ） 、６．５
〜７．８（ｍ、７Ｈ）、８．２５（ｄ、ｌＨ，Ｊ−５Ｈ
２）
〔試 験 例〕
（１） 水浸拘束ストレス潰瘍に対する抑制作用ＳＤ
系雌雄性ラット体重２００〜３００ｇ）を２４時間絶食
後、本発明に係るフェノキシプロピルアミン誘導体を３
２■／ｋｇ体重の用量で経口投与し、１時間後ストレス
ケージに入れて２３℃の水浴中で水浸拘束ストレスを負
荷した。ストレス負荷後７時間目にラットをエーテル致
死させ、胃を摘出しホルマリン処理後、腺胃部に発生し
た潰瘍の面積（−）を測定し、−匹あたりの損傷の総和
を潰瘍係数（Ｌｌｌｃｅｒ Ｉｎｄｅｘ）とした。nmr (CDCI 3) δ 1.2-2.7 (1,1
4H), 3.1-3.8 (s, 4H), 3.80 (S,
2B), 3,90Ct, 2H, J=BHz), 6.5
~7.8 (m, 7H), 8.25 (d, lH, J-5H
2) [Test example] (1) Inhibitory effect on water immersion restraint stress ulcer SD
After fasting for 24 hours, male and female rats weighing 200 to 300 g were given 3 phenoxypropylamine derivatives according to the present invention.
The animals were orally administered at a dose of 2 lb/kg body weight, and 1 hour later, they were placed in a stress cage and subjected to water immersion restraint stress in a water bath at 23°C. Seven hours after the stress load, rats were killed with ether, their stomachs were removed and treated with formalin, and the area (-) of ulcers that had developed in the glandular stomach was measured. ).
試験の結果、表に示す如く、本発明化合物の著明な抗潰
瘍作用を見い出した。また表に示されない本発明に係る
フェノキシプロピルアミン誘導体についても同様な抗潰
瘍作用を有することが確認された。As a result of the test, as shown in the table, the compound of the present invention was found to have a remarkable anti-ulcer effect. Furthermore, it was confirmed that the phenoxypropylamine derivative according to the present invention, which is not shown in the table, also has a similar anti-ulcer effect.
尚、表中の潰瘍形成阻害率（％）とは、本発明に係るフ
ェノキシプロピルアミン誘導体を経口投与したラットの
潰瘍係数を経口投与しないラットの潰瘍係数で除した値
を１がら引いて１００倍したものである。In addition, the ulcer formation inhibition rate (%) in the table is calculated by subtracting the value obtained by dividing the ulcer coefficient of rats to which the phenoxypropylamine derivative according to the present invention is orally administered by the ulcer coefficient of rats not orally administered, and subtracting the value by 100 times. This is what I did.
（２）エタノール潰瘍に対する抑制作用ＳＤ系雌雄性ラ
ット体重２００〜３００ｇ）を２４時間絶食後、本発明
に係るフェノキシプロピルアミン誘導体を３２ｍｇ／ｋ
ｇ体重の用量で経口投与し、１時間後エタノールを０．
５ｍｌ ／ １００ ｇ体重の用量で経口投与した。エ
タノール投与１時間後にエーテル致死させ、胃を摘出し
ホルマリン処理後、腺胃部に発生した損傷の面積（−）
を測定し、−匹あたりの損傷の総和をｆｔ瘍係数（Ｕｌ
ｃｅｒ Ｉｎｄｅｘ）とした。(2) Suppressive effect on ethanol ulcer After fasting for 24 hours in male and female SD rats (body weight 200-300 g), 32 mg/kg of the phenoxypropylamine derivative according to the present invention was administered.
g of body weight, and 1 hour later, 0.0 g of ethanol was administered.
It was administered orally at a dose of 5 ml/100 g body weight. After 1 hour of ethanol administration, the stomach was removed and treated with formalin, and the area of damage caused in the glandular stomach (-)
-The total damage per animal was calculated as the ft tumor coefficient (Ul
cer Index).
試験の結果、表に示す如く、本発明化合物の著明な抗潰
瘍作用を見い出した。また、表に示されない本発明に係
るフェノキシプロピルアミン誘導体についても同様な抗
潰瘍作用を有することが確認された。As a result of the test, as shown in the table, the compound of the present invention was found to have a remarkable anti-ulcer effect. Furthermore, it was confirmed that the phenoxypropylamine derivative according to the present invention, which is not shown in the table, also has a similar anti-ulcer effect.
尚、表中の潰瘍形成阻害率（％）とは、本発明に係るフ
ェノキシプロピルアミン誘導体を経口投与したラットの
潰瘍係数を経口投与しないラットの潰瘍係数で除した値
を１から引いて１００倍したものである。In addition, the ulcer formation inhibition rate (%) in the table is 100 times the value obtained by dividing the ulcer coefficient of rats to which the phenoxypropylamine derivative according to the present invention is orally administered by the ulcer coefficient of rats not orally administered. This is what I did.
ＩＣＲ系雄性マウス（５週令）を用いて経口投与による
急性毒性試験を行った。本発明の化合物をＬ Ｄ ｓｏ
値はいずれも１０００＋ａｇ／ｋｇ以上であり、有効量
に比べて高い安全性が確認された。An acute toxicity test was conducted by oral administration using ICR male mice (5 weeks old). The compound of the present invention is L D so
All values were 1000+ag/kg or higher, confirming high safety compared to the effective dose.
本発明によれば新規なフェノキシプロピルアミン誘導体
およびこれを含有する抗潰瘍剤が提供される。本発明の
上記化合物はすぐれた抗潰瘍作用を有することが明らか
にされた。即ち胃酸分泌を抑制することにより潰瘍の治
癒を促進し、さらに強力な防御因子増強作用により投与
中止後の再発を防止することができるので胃潰瘍などの
治療薬として有効に使用することができる。According to the present invention, a novel phenoxypropylamine derivative and an antiulcer agent containing the same are provided. It has been revealed that the above compounds of the present invention have excellent anti-ulcer effects. That is, it promotes the healing of ulcers by suppressing gastric acid secretion, and furthermore, it can prevent recurrence after discontinuation of administration due to its strong protective factor-enhancing action, so it can be effectively used as a therapeutic agent for gastric ulcers and the like.
Claims (1)
れぞれ低級アルキル基を示すか、またはＲ＿１とＲ＿２
がいっしょになって式▲数式、化学式、表等があります
▼（ｍは４または５である）を有する基を示し、Ａは式
−ＣＨ＝Ｎ−または−Ｎ＝ＣＨ−を有する基を示し、ｎ
は１乃至５の整数を示す。〕で表わされるフェノキシプ
ロピルアミン誘導体またはその生理学的に許容し得る塩
。 ２）請求項１に記載のフェノキシプロピルアミン誘導体
またはその生理学的に許容し得る塩を含有する抗潰瘍剤
。[Claims] 1) Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) [In the formula, R_1 and R_2 are the same or different and each represents a lower alkyl group, or R_1 and R_2
together indicate a group having the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (m is 4 or 5), and A indicates a group having the formula -CH=N- or -N=CH- , n
represents an integer from 1 to 5. ] A phenoxypropylamine derivative or a physiologically acceptable salt thereof. 2) An antiulcer agent containing the phenoxypropylamine derivative according to claim 1 or a physiologically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16663290A JPH07119225B2 (en) | 1990-06-27 | 1990-06-27 | Phenoxypropylamine derivative and antiulcer agent containing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16663290A JPH07119225B2 (en) | 1990-06-27 | 1990-06-27 | Phenoxypropylamine derivative and antiulcer agent containing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0459776A true JPH0459776A (en) | 1992-02-26 |
| JPH07119225B2 JPH07119225B2 (en) | 1995-12-20 |
Family
ID=15834885
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16663290A Expired - Lifetime JPH07119225B2 (en) | 1990-06-27 | 1990-06-27 | Phenoxypropylamine derivative and antiulcer agent containing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07119225B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994012473A1 (en) * | 1992-11-20 | 1994-06-09 | Kaken Pharmaceutical Co., Ltd. | Acetamide derivative |
| WO1997003077A1 (en) * | 1995-07-12 | 1997-01-30 | Yungjin Pharmaceutical Co., Ltd. | Benz- or pyrido-imidazole derivatives |
-
1990
- 1990-06-27 JP JP16663290A patent/JPH07119225B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994012473A1 (en) * | 1992-11-20 | 1994-06-09 | Kaken Pharmaceutical Co., Ltd. | Acetamide derivative |
| WO1997003077A1 (en) * | 1995-07-12 | 1997-01-30 | Yungjin Pharmaceutical Co., Ltd. | Benz- or pyrido-imidazole derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07119225B2 (en) | 1995-12-20 |
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