JPH0774205B2 - Novel imidazole derivative - Google Patents
Novel imidazole derivativeInfo
- Publication number
- JPH0774205B2 JPH0774205B2 JP61287775A JP28777586A JPH0774205B2 JP H0774205 B2 JPH0774205 B2 JP H0774205B2 JP 61287775 A JP61287775 A JP 61287775A JP 28777586 A JP28777586 A JP 28777586A JP H0774205 B2 JPH0774205 B2 JP H0774205B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- methyl
- group
- methylimidazole
- lower alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000002460 imidazoles Chemical class 0.000 title claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- -1 α-methylbenzyl group Chemical group 0.000 description 62
- 150000001875 compounds Chemical class 0.000 description 43
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- HAHBBDSJTSRKCC-UHFFFAOYSA-N C12C(C=CC=C1C)(C)O2.[K] Chemical compound C12C(C=CC=C1C)(C)O2.[K] HAHBBDSJTSRKCC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000003925 brain function Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- BLNGVSNTBOHTLC-UHFFFAOYSA-N 1,6-dimethyl-7-oxabicyclo[4.1.0]hepta-2,4-diene Chemical compound C1=CC=CC2(C)C1(C)O2 BLNGVSNTBOHTLC-UHFFFAOYSA-N 0.000 description 2
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- BNYKZFOZWZMEJD-UHFFFAOYSA-N 3-methylimidazole-4-carbaldehyde Chemical compound CN1C=NC=C1C=O BNYKZFOZWZMEJD-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 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 2
- 241000699670 Mus sp. Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000003496 anti-amnesic effect Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- PXGQMYCEAWZJJF-UHFFFAOYSA-N (3-methylimidazol-4-yl)methanol Chemical compound CN1C=NC=C1CO PXGQMYCEAWZJJF-UHFFFAOYSA-N 0.000 description 1
- GIWQSPITLQVMSG-UHFFFAOYSA-N 1,2-dimethylimidazole Chemical compound CC1=NC=CN1C GIWQSPITLQVMSG-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- FOYWCEUVVIHJKD-UHFFFAOYSA-N 2-methyl-5-(1h-pyrazol-5-yl)pyridine Chemical compound C1=NC(C)=CC=C1C1=CC=NN1 FOYWCEUVVIHJKD-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- HYAUYIZRVCJJEM-UHFFFAOYSA-N CC(=O)OCc1cncn1C Chemical compound CC(=O)OCc1cncn1C HYAUYIZRVCJJEM-UHFFFAOYSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000037396 body weight Effects 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
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- QDYTUZCWBJRHKK-UHFFFAOYSA-N imidazole-4-methanol Chemical compound OCC1=CNC=N1 QDYTUZCWBJRHKK-UHFFFAOYSA-N 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 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
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- JTQISXJVBBQTEA-UHFFFAOYSA-M sodium 2,6-dimethylbenzenethiolate Chemical compound CC1=C(C(=CC=C1)C)[S-].[Na+] JTQISXJVBBQTEA-UHFFFAOYSA-M 0.000 description 1
- UGOOLIMBWSFDJH-UHFFFAOYSA-M sodium;4-benzylphenolate Chemical compound [Na+].C1=CC([O-])=CC=C1CC1=CC=CC=C1 UGOOLIMBWSFDJH-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は脳機能改善薬、抗健忘症剤、抗老人性痴呆症薬
として有用な新規イミダゾール誘導体に関する。TECHNICAL FIELD The present invention relates to a novel imidazole derivative useful as a brain function improving agent, an antiamnestic agent, and an anti-senile dementia agent.
イミダゾール誘導体としては例えば特開昭56-32463号、
56-128767号、56-128768号、57-149273号、58-18365
号、58-105970号公報に記載されているものが知られて
いるが、本発明の化合物とは置換基に大きな差異が見ら
れる。またこれらの公知化合物についても脳機能改善薬
としての有用性については全く明らかにされていない。As the imidazole derivative, for example, JP-A-56-32463,
56-128767, 56-128768, 57-149273, 58-18365
No. 58-105970, the substituents of the compound of the present invention are significantly different from those of the compound of the present invention. Further, the utility of these known compounds as brain function improving drugs has not been clarified at all.
本発明は一般式［Ｉ］ 式中、R1は低級アルキル基であり、R2、R3はそれぞれ水
素原子、低級アルキル基またはSR5（ここでR5は水素原
子または低級アルキル基である。）であり、R4は置換フ
エニル基または、置換ピリジル基（ここで、置換基は、
水素原子、低級アルキル基、低級アラルキル基またはハ
ロゲン原子である。）であり、Ｘは酸素原子、硫黄原子
または、イミノ基（該イミノ基は低級アルキル基によっ
て置換されていてもよい。）であり、ｍおよびｎは、R4
が置換ピリジル基の場合は、ｍが１又は２、ｎが０、１
又は２であり、R4が置換フエニル基の場合は、ｍ、ｎは
それぞれ０、１又は２であるが、ｎとｍは同時に０でな
いものする。］ で表わされる新規イミダゾール誘導体またはその薬理学
的に許容しうる塩類に関するものである。The present invention has the general formula [I] In the formula, R 1 is a lower alkyl group, R 2 and R 3 are each a hydrogen atom, a lower alkyl group or SR 5 (wherein R 5 is a hydrogen atom or a lower alkyl group), and R 4 is A substituted phenyl group or a substituted pyridyl group (wherein the substituent is
It is a hydrogen atom, a lower alkyl group, a lower aralkyl group or a halogen atom. ), X is an oxygen atom, a sulfur atom or an imino group (the imino group may be substituted by a lower alkyl group), and m and n are R 4
Is a substituted pyridyl group, m is 1 or 2, n is 0, 1
Or 2, and when R 4 is a substituted phenyl group, m and n are 0, 1 or 2, respectively, but n and m are not 0 at the same time. ] It is related with the novel imidazole derivative represented by these, or its pharmacologically acceptable salt.
本発明の新規な化合物は一般式〔Ｉ〕で表わされるもの
であり、式〔Ｉ〕中のR1、R2、R3、R5の低級アルキル
基、R4の置換基としての低級アルキル基さらにはＸがイ
ミノ基である場合の置換基としての低級アルキル基とし
ては、メチル基、エチル基、プロピル基、ブチル基など
を例示することができ、R4の置換基としての低級アラル
キル基としてはベンジル基、α−メチルベンジル基、
α，α−ジメチルベンジル基、フエネチル基、α，α−
ジメチルフエネチル基などを例示することができ、同様
にハロゲン原子としては塩素原子、臭素原子、フツ素原
子などを例示することができる。R4の好ましいものとし
ては、後述の表１に示すもののほか次の如き基を例示す
ることができる。The novel compound of the present invention is represented by the general formula [I], and the lower alkyl group of R 1 , R 2 , R 3 and R 5 in the formula [I] and the lower alkyl group as a substituent of R 4 are Examples of the lower alkyl group as a group and a substituent when X is an imino group include a methyl group, an ethyl group, a propyl group and a butyl group, and a lower aralkyl group as a substituent of R 4. As a benzyl group, α-methylbenzyl group,
α, α-dimethylbenzyl group, phenethyl group, α, α-
Examples thereof include a dimethylphenethyl group, and similarly, examples of the halogen atom include a chlorine atom, a bromine atom, and a fluorine atom. Preferred examples of R 4 include those shown in Table 1 below, and the following groups.
２−メチルフエニル基、３−メチルフエニル基、４−メ
チルフエニル基、2,3−ジメチルフエニル基、2,4−ジメ
チルフエニル基、3,4−ジメチルフエニル基、２−クロ
ロフエニル基、2,6−ジクロロフエニル基、３−ベンジ
ルフエニル基、２−α−メチルベンジル基、４−α−メ
チルベンジル基、２−ピリジル基、４−ピリジル基、４
−クロル−２−ピリジル基、６−クロル−２−ピリジル
基、２−メチル−４−ピリジル基、2,6−ジメチル−４
−ピリジル基、６−メチル−２−ピリジル基。2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group, 2,4-dimethylphenyl group, 3,4-dimethylphenyl group, 2-chlorophenyl group, 2,6 -Dichlorophenyl group, 3-benzylphenyl group, 2-α-methylbenzyl group, 4-α-methylbenzyl group, 2-pyridyl group, 4-pyridyl group, 4
-Chloro-2-pyridyl group, 6-chloro-2-pyridyl group, 2-methyl-4-pyridyl group, 2,6-dimethyl-4
-Pyridyl group, 6-methyl-2-pyridyl group.
また、本発明の化合物は遊離の状態であつても塩の形、
たとえば酸付加塩の形になつてもよい。酸付加塩として
は塩酸、硫酸、リン酸のごとき鉱酸、酢酸、マレイン
酸、クエン酸のごとき有機酸を例示することができる。Further, the compound of the present invention is in a salt form even in a free state,
For example, it may be in the form of an acid addition salt. Examples of the acid addition salt include mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and organic acids such as acetic acid, maleic acid and citric acid.
以下に本発明の化合物を具体的に例示する。The compounds of the present invention will be specifically exemplified below.
化合物番号１ ４−（2,6−ジメチルフエノキシ）メチ
ル−１−メチルイミダゾール 化合物番号２ ５−（2,6−ジメチルフエノキシ）メチ
ル−１−メチルイミダゾール 化合物番号３ ５−（２−メチルフエノキシ）メチル−
１−メチルイミダゾール 化合物番号４ ５−（３−メチルフエノキシ）メチル−
１−メチルイミダゾール 化合物番号５ ５−（４−メチルフエノキシ）メチル−
１−メチルイミダゾール 化合物番号６ ５−（２−クロロフエノキシ）メチル−
１−メチルイミダゾール 化合物番号７ ５−（２−ブロモフエノキシ）メチル−
１−メチルイミダゾール 化合物番号８ ４−（２−ベンジルフエノキシ）メチル
−１−メチルイミダゾール 化合物番号９ ５−（２−ベンジルフエノキシ）メチル
−１−メチルイミダゾール 化合物番号10 ５−（４−ベンジルフエノキシ）メチル
−１−メチルイミダゾール 化合物番号11 ５−（２−α−メチルベンジルフエノキ
シ）メチル−１−メチルイミダゾール 化合物番号12 ５−（２−α，α−ジメチルベンジルフ
エノキシ）メチル−１−メチルイミダゾール 化合物番号13 ４−（２−メチルフエニルチオ）メチル
−１−メチルイミダゾール 化合物番号14 ５−（２−メチルフエニルチオ）メチル
−１−メチルイミダゾール 化合物番号15 ５−（2,6−ジメチルフエニルチオ）メ
チル−１−メチルイミダゾール 化合物番号16 ５−（２−クロロフエニルチオ）メチル
−１−メチルイミダゾール 化合物番号17 ５−（２−ベンジルフエニルチオ）メチ
ル−１−メチルイミダゾール 化合物番号18 ５−（４−ベンジルフエニルチオ）メチ
ル−１−メチルイミダゾール 化合物番号19 ４−（Ｎ−メチル−２−トルイジノ）メ
チル−１−メチルイミダゾール 化合物番号20 ４−（Ｎ−メチル−2,6−キシリジノ）
メチル−１−メチルイミダゾール 化合物番号21 ５−（Ｎ−メチル−2,6−キシリジノ）
メチル−１−メチルイミダゾール 化合物番号22 ５−（Ｎ−メチル−2,6−クロロアニリ
ノ）メチル−１−メチルイミダゾール 化合物番号23 ５−（Ｎ−メチル−４−クロロアニリ
ノ）メチル−１−メチルイミダゾール 化合物番号24 ５−（2,6−キシリジノ）メチル−１−
メチルイミダゾール 化合物番号25 ４−（2,6−ジメチルベンジロキシ）メ
チル−１−メチルイミダゾール 化合物番号26 ５−（2,6−ジメチルベンジロキシ）メ
チル−１−メチルイミダゾール 化合物番号27 ５−（２−メチルベンジロキシ）メチル
−１−メチルイミダゾール 化合物番号28 ５−（４−メチルベンジロキシ）メチル
−１−メチルイミダゾール 化合物番号29 ５−（２−クロロベンジロキシ）メチル
−１−メチルイミダゾール 化合物番号30 ５−（２−ブロモベンジロキシ）メチル
−１−メチルイミダゾール 化合物番号31 ５−（２−ベンジルベンジロキシ）メチ
ル−１−メチルイミダゾール 化合物番号32 ４−（２−ピリジルアミノ）メチル−１
−メチルイミダゾール 化合物番号33 ５−（２−ピリジルアミノ）メチル−１
−メチルイミダゾール 化合物番号34 ５−（３−ピリジルアミノ）メチル−１
−メチルイミダゾール 化合物番号35 ５−（４−ピリジルアミノ）メチル−１
−メチルイミダゾール 化合物番号36 ５−（６−クロロ−２−ピリジルアミ
ノ）メチル−１−メチルイミダゾール 化合物番号37 ５−（４−クロロ−２−ピリジルアミ
ノ）メチル−１−メチルイミダゾール 化合物番号38 ５−（２−メチル−４−ピリジルアミ
ノ）メチル−１−メチルイミダゾール 化合物番号39 ５−（2,6−ジメチル−４−ピリジルア
ミノ）メチル−１−メチルイミダゾール 化合物番号40 ５−（２−ピリジルオキシ）メチル−１
−メチルイミダゾール 化合物番号41 ５−（２−ピリジルチオ）メチル−１−
メチルイミダゾール 化合物番号42 ５−（２−ピリジルメチルオキシ）メチ
ル−１−メチルイミダゾール 本発明の化合物で特に好ましいものを次の表１に挙げ
る。Compound No. 1 4- (2,6-Dimethylphenoxy) methyl-1-methylimidazole Compound No. 2 5- (2,6-Dimethylphenoxy) methyl-1-methylimidazole Compound No. 3 5- (2- Methylphenoxy) methyl-
1-Methylimidazole Compound No. 4 5- (3-Methylphenoxy) methyl-
1-Methylimidazole Compound No. 5 5- (4-Methylphenoxy) methyl-
1-Methylimidazole Compound No. 6 5- (2-chlorophenoxy) methyl-
1-Methylimidazole Compound No. 7 5- (2-Bromophenoxy) methyl-
1-Methylimidazole Compound No. 8 4- (2-Benzylphenoxy) methyl-1-methylimidazole Compound No. 9 5- (2-Benzylphenoxy) methyl-1-methylimidazole Compound No. 10 5- (4- Benzylphenoxy) methyl-1-methylimidazole Compound No. 11 5- (2-α-methylbenzylphenoxy) methyl-1-methylimidazole Compound No. 12 5- (2-α, α-dimethylbenzylphenoxy ) Methyl-1-methylimidazole Compound No. 13 4- (2-methylphenylthio) methyl-1-methylimidazole Compound No. 14 5- (2-methylphenylthio) methyl-1-methylimidazole Compound No. 15 5- (2,6-Dimethylphenylthio) methyl-1-methylimidazole Compound No. 16 5- (2-chlorophenyl) Thio) methyl-1-methylimidazole compound number 17 5- (2-benzylphenylthio) methyl-1-methylimidazole compound number 18 5- (4-benzylphenylthio) methyl-1-methylimidazole compound number 194 -(N-methyl-2-toluidino) methyl-1-methylimidazole Compound No. 20 4- (N-methyl-2,6-xylidino)
Methyl-1-methylimidazole Compound No. 21 5- (N-methyl-2,6-xylidino)
Methyl-1-methylimidazole compound number 22 5- (N-methyl-2,6-chloroanilino) methyl-1-methylimidazole compound number 23 5- (N-methyl-4-chloroanilino) methyl-1-methylimidazole compound number 24 5- (2,6-xylidino) methyl-1-
Methylimidazole Compound No. 25 4- (2,6-Dimethylbenzyloxy) methyl-1-methylimidazole Compound No. 26 5- (2,6-Dimethylbenzyloxy) methyl-1-methylimidazole Compound No. 27 5- (2- Methylbenzyloxy) methyl-1-methylimidazole compound number 28 5- (4-methylbenzyloxy) methyl-1-methylimidazole compound number 29 5- (2-chlorobenzyloxy) methyl-1-methylimidazole compound number 30 5 -(2-Bromobenzyloxy) methyl-1-methylimidazole Compound No. 31 5- (2-benzylbenzyloxy) methyl-1-methylimidazole Compound No. 32 4- (2-pyridylamino) methyl-1
-Methylimidazole Compound No. 33 5- (2-pyridylamino) methyl-1
-Methylimidazole Compound No. 34 5- (3-pyridylamino) methyl-1
-Methylimidazole Compound No. 35 5- (4-pyridylamino) methyl-1
-Methylimidazole Compound No. 36 5- (6-chloro-2-pyridylamino) methyl-1-methylimidazole Compound No. 37 5- (4-chloro-2-pyridylamino) methyl-1-methylimidazole Compound No. 38 5- (2 -Methyl-4-pyridylamino) methyl-1-methylimidazole Compound No. 39 5- (2,6-Dimethyl-4-pyridylamino) methyl-1-methylimidazole Compound No. 40 5- (2-pyridyloxy) methyl-1
-Methylimidazole Compound No. 41 5- (2-pyridylthio) methyl-1-
Methylimidazole Compound No. 42 5- (2-Pyridylmethyloxy) methyl-1-methylimidazole Particularly preferred compounds of the present invention are listed in Table 1 below.
〔製造方法〕 一般式〔Ｉ〕で表わされる新規なイミダゾール誘導体は
次の反応式に従つて製造することができる。 [Production Method] The novel imidazole derivative represented by the general formula [I] can be produced according to the following reaction formula.
（１） 化合物〔II〕は公知化合物であり、化合物〔II
I〕はピリジン溶媒中トリエチルアミン存在下で無水酢
酸と20〜150℃、好ましくは50〜130℃で反応させ、次い
で蒸発乾固させ、アセトニトリルやテトラヒドロフラン
（以下THFと略す）などの溶媒中、ハロゲン化アルキル
と０〜100℃、好ましくは20〜50℃で反応させることに
よつて得られる。化合物〔IV〕は化合物〔III〕を水酸
化ナトリウム、水酸化カリウムなどのアルカリ水溶液で
０〜100℃、好ましくは０〜50℃で加水分解した後、チ
オニルクロリドと20〜150℃、好ましくは50〜120℃で反
応させることにより得られる。 (1) Compound [II] is a known compound, and compound [II]
I] is reacted with acetic anhydride in the presence of triethylamine in a pyridine solvent at 20 to 150 ° C., preferably 50 to 130 ° C., then evaporated to dryness and halogenated in a solvent such as acetonitrile or tetrahydrofuran (hereinafter abbreviated as THF). It is obtained by reacting with an alkyl at 0 to 100 ° C, preferably 20 to 50 ° C. The compound [IV] is obtained by hydrolyzing the compound [III] with an aqueous alkali solution such as sodium hydroxide or potassium hydroxide at 0 to 100 ° C, preferably 0 to 50 ° C, and then thionyl chloride and 20 to 150 ° C, preferably 50 Obtained by reacting at ~ 120 ° C.
化合物〔Ｉ〕は化合物〔IV〕と化合物〔Ｖ〕のような金
属塩をジメチルホルムアミド（以下DMFと略す）、ジメ
チルホルムアミド（以下DMSOと略す）などの溶媒中20〜
150℃、好ましくは50〜100℃で反応させることによつて
得られる。Compound [I] is prepared by mixing a metal salt such as compound [IV] and compound [V] in a solvent such as dimethylformamide (hereinafter abbreviated as DMF), dimethylformamide (hereinafter abbreviated as DMSO), etc.
It is obtained by reacting at 150 ° C, preferably 50 to 100 ° C.
（２） 化合物〔VI〕は化合物〔II〕をジオキサン、TH
Fなどの溶媒中、二酸化マンガン、過マンガン酸カリウ
ムなどと20〜150℃好ましくは50〜100℃で反応させるこ
とによつて得られる。化合物〔Ｉ〕（Ｘ＝NH）は化合物
〔VI〕と化合物〔VII〕とを反応させイミンにした後、
水酸化ホウ素ナトリウムなどの還元剤と反応させること
によつて得られる。(2) Compound [VI] is obtained by converting Compound [II] into dioxane and TH.
It can be obtained by reacting with manganese dioxide, potassium permanganate or the like in a solvent such as F at 20 to 150 ° C, preferably 50 to 100 ° C. The compound [I] (X = NH) is converted into an imine by reacting the compound [VI] with the compound [VII].
It is obtained by reacting with a reducing agent such as sodium borohydride.
上記以外の化合物〔Ｉ〕についても、上記の方法に準じ
て合成することができる。Compounds [I] other than the above can also be synthesized according to the above method.
以下、実施例等により本発明を具体的に説明する。 Hereinafter, the present invention will be specifically described with reference to examples and the like.
参考例１ ５−ヒドロキシメチル−１−メチルイミダゾールの製造 ４−ヒドロキシメチルイミダゾール2.0g（20.3mmol）に
ピリジン10ml、トルエチルアミン10ml、無水酢酸10mlを
加え、100℃で２時間加熱した。反応混合物を減圧下濃
縮乾固し、残渣にアセトニトリル20ml、ヨウ化メチル10
mlを加え、室温で20時間攪拌した。反応混合物を減圧下
濃縮乾固し、エタノール10mlを加え、室温で１時間攪拌
した後、濃縮し、５−アセトキシメチル−１−メチルイ
ミダゾールを褐色液体として2.70g（収率86％）得た。
これに５％水酸化ナトリウム水溶液27mlを加え、室温で
１時間攪拌した後、2N塩酸で中和し、減圧下濃縮乾固し
た。得られた残渣をエタノール、トルエンで抽出し、５
−ヒドロキシメチル−１−メチルイミダゾールを無色結
晶として1.6g（収率82％）得た。Reference Example 1 Production of 5-hydroxymethyl-1-methylimidazole To 2.0 g (20.3 mmol) of 4-hydroxymethylimidazole, 10 ml of pyridine, 10 ml of toluethylamine and 10 ml of acetic anhydride were added, and heated at 100 ° C. for 2 hours. The reaction mixture was concentrated to dryness under reduced pressure, and 20 ml of acetonitrile and 10 ml of methyl iodide were added to the residue.
ml was added, and the mixture was stirred at room temperature for 20 hours. The reaction mixture was concentrated to dryness under reduced pressure, 10 ml of ethanol was added, and the mixture was stirred at room temperature for 1 hour and then concentrated to obtain 2.70 g (yield 86%) of 5-acetoxymethyl-1-methylimidazole as a brown liquid.
27 ml of a 5% aqueous sodium hydroxide solution was added thereto, and the mixture was stirred at room temperature for 1 hour, neutralized with 2N hydrochloric acid, and concentrated to dryness under reduced pressure. The obtained residue is extracted with ethanol and toluene, and then 5
1.6 g (yield 82%) of -hydroxymethyl-1-methylimidazole was obtained as colorless crystals.
融点114〜116℃ 実施例１ ５−（2,6−ジメチルフエノキシ）メチル−１−メチル
イミダゾール「化合物番号２」の製造 ５−ヒドロキシメチル−１−イミダゾール1.0g（8.9mmo
l）に塩化チオニル10mlを加え、100℃で0.5時間加熱し
た。反応混合物を減圧下濃縮乾固し、これに、2,6−キ
シレノールと水酸化カリウムより調製したカリウム2,6
−キシレノキシド3.6g（22.3mmol）のDMF溶液20mlを加
え、80℃で２時間加熱した。反応混合物を減圧下濃縮乾
固し、炭酸カリウム水溶液で中和した後、クロロホルム
抽出した。クロロホルム層を無水硫酸ナトリウムで乾
燥、減圧下濃縮した後、シリカゲルクロマトグラフイー
で精製し、目的物「化合物番号１」を淡褐色結晶として
0.87g（収率45％）得た。Melting point 114-116 ° C. Example 1 Preparation of 5- (2,6-dimethylphenoxy) methyl-1-methylimidazole “Compound No. 2” 5-hydroxymethyl-1-imidazole 1.0 g (8.9 mmo
10 ml of thionyl chloride was added to (l) and heated at 100 ° C. for 0.5 hours. The reaction mixture was concentrated to dryness under reduced pressure, and potassium 2,6 prepared from 2,6-xylenol and potassium hydroxide was added thereto.
20 ml of DMF solution containing 3.6 g (22.3 mmol) of xylenoxide was added and heated at 80 ° C for 2 hours. The reaction mixture was concentrated to dryness under reduced pressure, neutralized with an aqueous potassium carbonate solution, and extracted with chloroform. The chloroform layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified by silica gel chromatography to obtain the target compound "Compound No. 1" as light brown crystals.
0.87 g (yield 45%) was obtained.
融点208〜212℃（塩酸塩）1 H−核磁気共鳴スペクトル（重クロロホルム，δppm） 2.20（s,6H）,3.72（s,3H）,4.73（s,2H）,6.99（s,4
H）,7.48（s,1H） 実施例２ ５−（２−ベンジルフエノキシ）メチル−１−メチルイ
ミダゾール「化合物番号９」の製造 実施例１においてカリウム2,6−キシレノキシドのかわ
りにナトリウム２−ベンジルフエノキシドを用いて同様
に反応を行い、目的物「化合物番号９」を淡褐色液体と
して得た（収率56％）。Melting point 208-212 ° C (hydrochloride) 1 H-nuclear magnetic resonance spectrum (deuterated chloroform, δppm) 2.20 (s, 6H), 3.72 (s, 3H), 4.73 (s, 2H), 6.99 (s, 4)
H), 7.48 (s, 1H) Example 2 Preparation of 5- (2-benzylphenoxy) methyl-1-methylimidazole “Compound No. 9” In Example 1, sodium 2 was used instead of potassium 2,6-xylenoxide. The same reaction was carried out using -benzylphenoxide to obtain the target compound "Compound No. 9" as a pale brown liquid (yield 56%).
融点174〜175℃（塩酸塩）1 H−核磁気共鳴スペクトル（重クロロホルム，δppm） 3.28（s,3H）,3.92（s,2H）,4.90（s,2H）,6.90〜7.30
（m,10H）,7.38（s,1H） 実施例３ ５−（４−ベンジルフエノキシ）メチル−１−メチルイ
ミダゾール「化合物番号10」の製造 実施例１においてカリウム2,6−キシレノキシドのかわ
りにナトリウム４−ベンジルフエノキシドを用いて同様
に反応を行い、目的物「化合物番号10」を淡黄色液体と
して得た（収率64％）。Melting point 174 to 175 ° C (hydrochloride) 1 H-nuclear magnetic resonance spectrum (deuterated chloroform, δppm) 3.28 (s, 3H), 3.92 (s, 2H), 4.90 (s, 2H), 6.90 to 7.30
(M, 10H), 7.38 (s, 1H) Example 3 Preparation of 5- (4-benzylphenoxy) methyl-1-methylimidazole "Compound No. 10" In Example 1, instead of potassium 2,6-xylenoxide. Similarly, sodium 4-benzylphenoxide was used as the reaction product to obtain the target compound "Compound No. 10" as a pale yellow liquid (yield 64%).
融点172〜174℃（塩酸塩） 実施例４ ５−（2,6−ジメチルフエニルチオ）メチル−１−メチ
ルイミダゾール「化合物番号15」の製造 実施例１においてカリウム2,6−キシレノキシドのかわ
りにナトリウム2,6−ジメチルチオフエノキシドを用い
て同様に反応を行い、目的物「化合物番号15」を褐色液
体として得た（収率52％） 融点230〜235℃（塩酸塩）1 H−核磁気共鳴スペクトル（重クロロホルム，δppm） 2.36（s,6H）,3.63（s,3H）,3.77（s,2H）,7.10（s,4
H）,7.38（s,1H） 実施例５ ５−（Ｎ−メチル−2,6−−キシリジノ）メチル−１−
メチルイミダゾール「化合物番号21」の製造 実施例１においてカリウム2,6−キシレノキシドのかわ
りにナトリウムＮ−メチル−2,6−ジメチルアニリドを
用いて同様に反応を行い、目的物「化合物番号21」を黄
色液体として得た（収率34％）。1 H−核磁気共鳴スペクトル（重クロロホルム，δppm） 2.32（s,6H）,2.76（s,3H）,3.50（s,3H）,4.16（s,2
H）,7.03（s,4H）,7.44（s,1H） 実施例６ ５−2,6−ジエチルベンジロキシ）メチル−１−メチル
イミダゾール「化合物番号26」の製造 実施例１においてカリウム2,6−キシレノキシドのかわ
りにナトリウム2,6−ジメチルベンジロキシドを用いて
同様に反応を行い、目的物「化合物番号26」を淡褐色液
体として得た（収率62％）。Melting point 172-174 ° C. (hydrochloride) Example 4 Preparation of 5- (2,6-dimethylphenylthio) methyl-1-methylimidazole “Compound No. 15” In Example 1, instead of potassium 2,6-xylenoxide. The same reaction was carried out using sodium 2,6-dimethylthiophenoxide to obtain the target compound "Compound No. 15" as a brown liquid (yield 52%). Melting point 230-235 ° C (hydrochloride) 1 H- Nuclear magnetic resonance spectrum (deuterated chloroform, δppm) 2.36 (s, 6H), 3.63 (s, 3H), 3.77 (s, 2H), 7.10 (s, 4)
H), 7.38 (s, 1H) Example 5 5- (N-methyl-2,6-xylidino) methyl-1-
Production of Methylimidazole "Compound No. 21" In the same manner as in Example 1, sodium N-methyl-2,6-dimethylanilide was used in place of potassium 2,6-xylenoxide to carry out the same reaction to give the desired product "Compound No. 21". Obtained as a yellow liquid (yield 34%). 1 H-nuclear magnetic resonance spectrum (deuterated chloroform, δppm) 2.32 (s, 6H), 2.76 (s, 3H), 3.50 (s, 3H), 4.16 (s, 2
H), 7.03 (s, 4H), 7.44 (s, 1H) Example 6 Preparation of 5-2,6-diethylbenzyloxy) methyl-1-methylimidazole “Compound No. 26” In Example 1, potassium 2,6 -Sodium 2,6-dimethylbenziloxide was used instead of xylenoxide to carry out the same reaction to obtain the target compound "Compound No. 26" as a light brown liquid (yield 62%).
融点168〜172℃（塩酸塩）1 H−核磁気共鳴スペクトル（重クロロホルム，δppm） 2.34（s,6H）,3.65（s,3H）,4.52（s,2H）,4.56（s,2
H）,7.06（s,4H）,7.45（s,1H） 参考例２ ５−ホルミル−１−メチルイミダゾールの製造 ５−ヒドロキシメチル−１−メチルイミダゾール0.8g
（7.1mmol）、二酸化マンガン7.0gにジオキサン60mlを
加え、４時間加熱還流した。反応液を濾過し、固体をジ
オキサン50mlで２回洗浄し、濾液を合わせて減圧下濃縮
し、５−ホルミル−１−メチルイミダゾールを無色固体
として0.43g（収率53％）得た。Melting point 168-172 ° C (hydrochloride) 1 H-nuclear magnetic resonance spectrum (deuterated chloroform, δppm) 2.34 (s, 6H), 3.65 (s, 3H), 4.52 (s, 2H), 4.56 (s, 2
H), 7.06 (s, 4H), 7.45 (s, 1H) Reference Example 2 Preparation of 5-formyl-1-methylimidazole 5-hydroxymethyl-1-methylimidazole 0.8 g
(7.1 mmol) and 60 g of dioxane were added to 7.0 g of manganese dioxide, and the mixture was heated under reflux for 4 hours. The reaction solution was filtered, the solid was washed twice with 50 ml of dioxane, the filtrates were combined and concentrated under reduced pressure to obtain 0.43 g (yield 53%) of 5-formyl-1-methylimidazole as a colorless solid.
実施例７ ５−（３−ピリジルアミノ）メチル−１−メチルイミダ
ゾール「化合物番号34」の製造 ５−ホルミル−１−メチルイミダゾール0.3g（2.7mmo
l）、３−アミノピリジン0.3g（3.2mmol）を加工、留出
する水をぬきながら３時間加熱還流した。反応混合物を
減圧下濃縮乾固し、エタノール20mlに溶解させ、室温で
水素化ホウ素ナトリウム0.11g（2.9mmol）を約10分間で
加工、そのまま３時間攪拌した。反応混合物に2N塩酸を
加工中和した後、クロロホルムで抽出した。クロロホル
ム層を無水硫酸ナトリウムで乾燥後、減圧濃縮し、シリ
カゲルカラムクロマトグライフイーで精製し、目的物
「化合物番号34」を黄色結晶として0.15g（収率29％）
得た。Example 7 Preparation of 5- (3-pyridylamino) methyl-1-methylimidazole "Compound No. 34" 5-formyl-1-methylimidazole 0.3 g (2.7 mmo
l) and 3-aminopyridine (0.3 g, 3.2 mmol) were processed, and the mixture was heated under reflux for 3 hours while removing distilled water. The reaction mixture was concentrated to dryness under reduced pressure, dissolved in 20 ml of ethanol, 0.11 g (2.9 mmol) of sodium borohydride was processed at room temperature for about 10 minutes, and the mixture was stirred for 3 hours as it was. The reaction mixture was processed and neutralized with 2N hydrochloric acid, and then extracted with chloroform. The chloroform layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography, 0.15 g (yield 29%) of the desired product, "Compound No. 34" as yellow crystals.
Obtained.
融点206〜209℃（塩酸塩）1 H−核磁気共鳴スペクトル（重クロロホルム，δppm） 3.64（s,3H）,4.27（s,2H）,7.00（s,1H）,6.9〜7.2
（m,2H）,7.40（s,1H）,7.95〜8.10（m,2H） 〔作用および効果〕 本発明の一般式〔Ｉ〕の化合物およびその酸付加塩は優
れた抗脳虚血作用および抗低圧低酸素作用を示し、脳機
能改善剤または抗健忘症剤として有用であり、また老人
性痴呆症治療剤としても有用である。本発明に係わる化
合物は、それ自体単独で投与してもよいが、必要又は所
望により種々の剤型として経口的又は非経口的に投与す
ることができる。Melting point 206-209 ° C (hydrochloride) 1 H-nuclear magnetic resonance spectrum (deuterated chloroform, δppm) 3.64 (s, 3H), 4.27 (s, 2H), 7.00 (s, 1H), 6.9-7.2
(M, 2H), 7.40 (s, 1H), 7.95 to 8.10 (m, 2H) [Action and effect] The compound of the general formula [I] and its acid addition salt of the present invention have excellent anti-cerebral ischemic action and It exhibits an antihypertensive hypoxic effect and is useful as a brain function improving agent or an antiamnestic agent, and also as a therapeutic agent for senile dementia. The compound according to the present invention may be administered alone, but may be orally or parenterally administered in various dosage forms as necessary or desired.
抗脳虚血試験 体重22〜30gのddY系雄マウスを１群６匹使用した。被検
薬を腹腔内（i.p.）に投与し、投与30分後に断頭した。
断頭後、頭部のgasping様呼吸が停止するまでの時間を
測定し、これを有意に延長する最小の投与量を求めた。Anti-Cerebral Ischemia Test A group of 6 ddY male mice weighing 22 to 30 g was used. The test drug was administered intraperitoneally (ip) and decapitated 30 minutes after the administration.
After decapitation, the time until the gasping-like breathing of the head stopped was measured, and the minimum dose that significantly prolongs this was determined.
抗低圧低酸素試験 体重23〜28gのddY系雄マウスを１群７〜10匹使用した。
被検薬を腹腔内（i.p.）に投与30分後、デシケータ内に
入れ180mmHgまで減圧した後から死亡までの時間（生存
時間）を測定し、これを有意に延長する最小の投与量を
求めた。Anti-hypobaric hypoxia test A group of 7 to 10 male ddY mice having a body weight of 23 to 28 g was used.
Thirty minutes after the test drug was administered intraperitoneally (ip), it was placed in a desiccator and decompressed to 180 mmHg until the death (survival time) was measured, and the minimum dose that significantly prolongs this was determined. .
結果を次表に示す。The results are shown in the table below.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｃ０７Ｄ 233/86 233/88 401/12 ２３３ // Ａ６１Ｋ 31/415 ＡＡＭ 31/44 (56)参考文献 米国特許4505918（ＵＳ，Ａ) Ｊ．Ｃｈｅｍ．Ｓｏｃ．，Ｐｅｒｋｉｎ Ｔｒａｎｓ．１（15），（1972），Ｐ. 1955−1960─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification number Office reference number FI technical display location C07D 233/86 233/88 401/12 233 // A61K 31/415 AAM 31/44 (56) Reference Literature US Pat. No. 4,505,918 (US, A) J. Am. Chem. Soc. , Perkin Trans. 1 (15), (1972), P. 1955-1960
Claims (1)
水素原子、低級アルキル基またはSR5（ここでR5は水素
原子または低級アルキル基である。）であり、R4は置換
フエニル基または、置換ピリジル基（ここで、置換基
は、水素原子、低級アルキル基、低級アラルキル基また
はハロゲン原子である。）であり、Ｘは酸素原子、硫黄
原子または、イミノ基（該イミノ基は低級アルキル基に
よって置換されていてもよい。）であり、ｍ及びｎは、
R4が置換ピリジル基の場合は、ｍが１又は２、ｎが０、
１又は２であり、R4が置換フエニル基の場合は、ｍ、ｎ
はそれぞれ０、１又は２であるが、ｎとｍは同時に０で
ないものとする。］ で表わされる新規イミダゾール誘導体またはその薬理学
的に許容しうる塩類。1. A general formula [I] [Wherein, R 1 is a lower alkyl group, R 2 and R 3 are a hydrogen atom, a lower alkyl group or SR 5 (wherein R 5 is a hydrogen atom or a lower alkyl group), and R 4 Is a substituted phenyl group or a substituted pyridyl group (wherein the substituent is a hydrogen atom, a lower alkyl group, a lower aralkyl group or a halogen atom), and X is an oxygen atom, a sulfur atom or an imino group ( The imino group may be substituted by a lower alkyl group), and m and n are
When R 4 is a substituted pyridyl group, m is 1 or 2, n is 0,
1 or 2 and R 4 is a substituted phenyl group, m, n
Are 0, 1 or 2, respectively, but n and m are not 0 at the same time. ] The novel imidazole derivative represented by these, or its pharmacologically acceptable salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61287775A JPH0774205B2 (en) | 1986-12-04 | 1986-12-04 | Novel imidazole derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61287775A JPH0774205B2 (en) | 1986-12-04 | 1986-12-04 | Novel imidazole derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63141969A JPS63141969A (en) | 1988-06-14 |
| JPH0774205B2 true JPH0774205B2 (en) | 1995-08-09 |
Family
ID=17721588
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61287775A Expired - Lifetime JPH0774205B2 (en) | 1986-12-04 | 1986-12-04 | Novel imidazole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0774205B2 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9127304D0 (en) * | 1991-12-23 | 1992-02-19 | Boots Co Plc | Therapeutic agents |
| US5728842A (en) * | 1992-06-30 | 1998-03-17 | Smithkline Beecham Corporation | Substituted imidazolyl-alkylthio-alkanoic acids |
| GB9213934D0 (en) * | 1992-06-30 | 1992-08-12 | Smithkline Beecham Corp | Chemical compounds |
| GB9312893D0 (en) * | 1993-06-22 | 1993-08-04 | Boots Co Plc | Therapeutic agents |
| WO1995004723A1 (en) * | 1993-08-04 | 1995-02-16 | Yamanouchi Pharmaceutical Co., Ltd. | Imidazolylalkylamine derivative and pharmaceutical composition thereof |
| DE60205338T2 (en) | 2001-01-30 | 2006-06-01 | Zenyaku Kogyo K.K. | HETEROCYCLIC COMPOUNDS AND AGENTS THAT IMPROVE THE BRAIN FUNCTION AND INCLUDE THESE COMPOUNDS AS AN ACTIVE SUBSTANCE |
| KR101176699B1 (en) | 2006-10-19 | 2012-08-23 | 에프. 호프만-라 로슈 아게 | Aminomethyl-4-imidazoles |
| US20080146523A1 (en) * | 2006-12-18 | 2008-06-19 | Guido Galley | Imidazole derivatives |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4505918A (en) | 1982-11-08 | 1985-03-19 | Merck & Co., Inc. | 4-[2-Pyridinylthio(oxy or amino)methyl]-1H-imidazoles and derivatives |
-
1986
- 1986-12-04 JP JP61287775A patent/JPH0774205B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4505918A (en) | 1982-11-08 | 1985-03-19 | Merck & Co., Inc. | 4-[2-Pyridinylthio(oxy or amino)methyl]-1H-imidazoles and derivatives |
Non-Patent Citations (1)
| Title |
|---|
| Ｊ．Ｃｈｅｍ．Ｓｏｃ．，ＰｅｒｋｉｎＴｒａｎｓ．１（１５），（１９７２），Ｐ．１９５５−１９６０ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63141969A (en) | 1988-06-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4886803A (en) | Benzimidazole derivatives | |
| US4181658A (en) | Certain nicotinamido-n-benzoic acid derivatives | |
| JPH10503501A (en) | Indole, indazole, pyridopyrrole and pyridopyrazole derivatives having anti-asthma, anti-allergy, anti-inflammatory and immunomodulatory effects | |
| US4166851A (en) | Certain imidazo(1,2a)pyridine derivatives | |
| US20060128757A1 (en) | Pyridine derivatives useful as cyclooxygenase inhibitor | |
| US5663340A (en) | N-(2-amino-4,6-dichloropyrimidine-5-yl)formamide, and a process for its preparation | |
| US4148801A (en) | 3-[(Chlorophenylsulfonyl)methyl]-1,2,4-oxadiazole-5-carboxylic acid derivatives | |
| US20100144782A1 (en) | Derivatives of 7-alkynyl-1,8-naphthyridones, preparation method thereof and use of same in therapeutics | |
| KR20070043779A (en) | 4-phenyl-pyrimidine-2-carbonitrile derivatives | |
| JPH0774205B2 (en) | Novel imidazole derivative | |
| KR20010085852A (en) | 2,3-disubstituted pyridine derivatives, process for the preparation thereof, drug compositions containing the same and intermediates for the preparation | |
| JP2707936B2 (en) | β-oxo-β-benzenepropanethioamide derivative | |
| KR860000104B1 (en) | Process for preparing 2-pyridine carboxamide derivatives | |
| EP0623023A1 (en) | Retroreverse pyrrole-amidino oligopeptide anticancer agent analogues, preparation of same, and pharmaceutical compositions containing such analogues | |
| JPS62252780A (en) | Novel indenothiazole derivative and production thereof | |
| JPH0692915A (en) | 1,2-diaminocyclobutene-3,4-dione derivative and its use | |
| JPS6055069B2 (en) | N-pyridyl-amide of 1-phenyl-cyclopentanecarboxylic acid, its production method, and anti-inflammatory and antitussive agents containing it as an active ingredient | |
| US4495194A (en) | Antihypertensive isoindole derivatives | |
| US6288271B1 (en) | Process for the preparation of (2,2,2-trifluoroethoxy)benzoic acids | |
| US4168313A (en) | Phthalidyl 2-(3'-trifluoromethyl-anilino)-pyridine-3-carboxylate and its salts | |
| JPH027952B2 (en) | ||
| JPH0629264B2 (en) | 2-amino-5-hydroxy-4-pyrimidone | |
| JP2831000B2 (en) | (2-aminobenzoyl) acetic acid ester derivative | |
| JPH064625B2 (en) | Substituted isoquinoline derivative and anti-ulcer agent | |
| JPH0378384B2 (en) |