JPS63150266A - Benzylimidazole derivative - Google Patents
Benzylimidazole derivativeInfo
- Publication number
- JPS63150266A JPS63150266A JP61294668A JP29466886A JPS63150266A JP S63150266 A JPS63150266 A JP S63150266A JP 61294668 A JP61294668 A JP 61294668A JP 29466886 A JP29466886 A JP 29466886A JP S63150266 A JPS63150266 A JP S63150266A
- Authority
- JP
- Japan
- Prior art keywords
- group
- compound
- lower alkyl
- methylimidazole
- hydrogen atom
- 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
- 150000004962 phenylmethylimidazoles Chemical class 0.000 title claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 41
- 239000003814 drug Substances 0.000 abstract description 9
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 8
- 229910052736 halogen Inorganic materials 0.000 abstract description 5
- 150000002367 halogens Chemical class 0.000 abstract description 5
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 abstract description 3
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 3
- 206010039966 Senile dementia Diseases 0.000 abstract description 3
- 208000000044 Amnesia Diseases 0.000 abstract description 2
- 208000031091 Amnestic disease Diseases 0.000 abstract description 2
- 230000006986 amnesia Effects 0.000 abstract 1
- 230000002490 cerebral effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 abstract 1
- -1 1-methylvinyl group Chemical group 0.000 description 38
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 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
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
- 239000003795 chemical substances by application Substances 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 1
- IWSGKSUCFVOWQU-UHFFFAOYSA-N 2-(2-bromophenyl)-1,3-dioxolane Chemical compound BrC1=CC=CC=C1C1OCCO1 IWSGKSUCFVOWQU-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- WWEDEECRSOOIGH-UHFFFAOYSA-N 5-[(2,6-dimethylphenyl)methyl]-1h-imidazole Chemical compound CC1=CC=CC(C)=C1CC1=CN=CN1 WWEDEECRSOOIGH-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003496 anti-amnesic effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 238000007912 intraperitoneal administration Methods 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
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は脳機能改善薬、抗健忘症薬、抗老人性痴呆症薬
として有用にベンジルイミダゾール誘導体に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to benzylimidazole derivatives useful as brain function improving drugs, anti-amnesia drugs, and anti-senile dementia drugs.
イミダゾール誘導体としては例えば特開昭５６−３２４
６３号、５６−１２８７６７号、５６−１２８７６８号
、５７−１４９２７３号、５Ｂ−１８３６５号、５Ｂ−
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。Examples of imidazole derivatives include JP-A-56-324
No. 63, No. 56-128767, No. 56-128768, No. 57-149273, No. 5B-18365, No. 5B-
Although the compound described in Japanese Patent No. 105970 is known, there are major differences in substituents from the compound of the present invention. Furthermore, the usefulness of these known compounds as brain function improving drugs has not been clarified at all.
本発明は一般式（１）
〔式中、Ｒ１は水素原子であるかあるいはヒドロキシ基
で置換されていてもよい低級アルキル基であり、Ｒ２は
水素原子、低級アルキル基、フェニル基、ハロゲン原子
又はメルカプト基でありＲ３は水素原子、低級アルキル
基又はハロゲン原子であり、Ｒ４は低級アルキル基、ハ
ロゲン原子、ビトロキシ基、エチレンジオキシメチル基
、アミノ基又はニトロ基であり、Ｒ５は水素原子、ヒド
ロキシ基又はアルコキシ基（該アルコキシ基はハロゲン
原子又はアルケニル基で置換されていてもよい。）であ
り、７は１ないし３の整数である。但し、Ｒ１が水素原
子または低級アルキル基であり、Ｒ２およびＲ３が共に
水素原子であり、Ｒ５が水素原子又はヒドロキシ基であ
り、かつＲ４が低級アルキル基であるものを除く。〕で
表わされるベンジルイミダゾール誘導体またはその薬学
的に許容しうる塩類に関するものである。The present invention relates to general formula (1) [wherein R1 is a hydrogen atom or a lower alkyl group which may be substituted with a hydroxy group, and R2 is a hydrogen atom, a lower alkyl group, a phenyl group, a halogen atom or It is a mercapto group, R3 is a hydrogen atom, a lower alkyl group, or a halogen atom, R4 is a lower alkyl group, a halogen atom, a bitroxy group, an ethylenedioxymethyl group, an amino group, or a nitro group, and R5 is a hydrogen atom, a hydroxy group or an alkoxy group (the alkoxy group may be substituted with a halogen atom or an alkenyl group), and 7 is an integer of 1 to 3. However, this excludes those in which R1 is a hydrogen atom or a lower alkyl group, R2 and R3 are both a hydrogen atom, R5 is a hydrogen atom or a hydroxy group, and R4 is a lower alkyl group. ] or its pharmaceutically acceptable salts.
ｃ本発明の物質〕
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（１）中のＲＩ、Ｒ２、Ｒ３およびＲ４が示
す低級アルキル基としては、メチル基、エチル基、プロ
ピル基、イソプロピル基、ブチル基などを例示すること
ができ、Ｒ３、Ｒ４およびＲ５の置換基としてのハロゲ
ン原子としては塩素原子、臭素原子、フッ素原子などを
例示することができ、Ｒ５のアルコキシ基としてはメト
キシ基、エトキシ基、プロポキシ基、ブトキシ基などを
例示することができ、Ｒ５の置換基としてのアルケニル
基としてはビニル基、１−メチルビニル基、２−メチル
ビニル基などを例示することができる。c Substance of the present invention] The novel compound of the present invention is represented by general formula [I], and the lower alkyl groups represented by RI, R2, R3 and R4 in formula (1) include methyl group, ethyl Examples of the halogen atom as a substituent for R3, R4 and R5 include a chlorine atom, a bromine atom, a fluorine atom, and the like. Examples of the alkoxy group include methoxy group, ethoxy group, propoxy group, butoxy group, etc., and examples of the alkenyl group as a substituent for R5 include vinyl group, 1-methylvinyl group, 2-methylvinyl group, etc. can do.
また、本発明の化合物は遊離の状態であっても塩の形、
たとえば酸付加塩の形になってもよい。In addition, the compound of the present invention may be in the form of a salt, even in a free state.
For example, it may be in the form of an acid addition salt.
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。Examples of acid addition salts 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 are specifically illustrated below.
化合物番号１ ４−（２−（１，３−ジオキソラン−２
−イル）フェニル−ヒドロキシコメチルイミダゾール化
合物番号２ ４−（２−（１，３−ジオキソラン−２−
イル）フェニル−ヒドロキシコメチル−１−イミダゾー
ル
化合物番号３ ５−Ｒ２−（ｉ、ａ−ジオキソラン−２
−イル）フェニル−ヒドロキシコメチル−１−イミダゾ
ール
化合物番号４ ５−（２−（１，３−ジオキソラン−２
−イル）フェニル−メトキシコメチル−１−イミダゾー
ル
化合物番号５４−（２−プロピエノキシ−（２，６−シ
メチルフエノキシ））メチルイミダゾール化合物番号６
４−（２−クロロ−２−プロピエノキシ）−（２，６−
シメチルフエノキシ）〕メチルイミダゾール
化合物番号７４−（２−クロロ−２−プロピエノキシ）
−（２，６−シメチルフユノキシ）〕〕メチルー１−メ
チルイミダゾー
ル合物番号８５−（２−クロロ−２−プロピエノキシ）
−（２，６−シメチルフエノキシ）〕〕メチルー１−メ
チルイミダゾー
ル合物番号９４−（２−クロロ−２−プロピエノキシ）
−（２−メチルフェノキシ）〕メチルイミダゾール化合
物番号１０５−（２−クロロ−２−プロピエノキシ）−
（２−メチルフェノキシ）〕〕メチルー１−メチルイミ
ダゾール ′
化合物番号１１ ４−（２，６−シメチルフエニル）メ
トキシ−１−メチルイミダゾール
化合物番号１２ ５−（２，６−シメチルフエニル）メ
トキシ−１−メチルイミダゾール
化合物番号１３ ４−（２−メチルフェニル）メトキシ
ーエ＝メチルイミダゾール
化合物番号１４ ５−（２−メチルフェニル）メトキシ
−１−メチルイミダゾール
化合物番号１５ ５−（２，３−ジメチルフェニル）メ
トキシ−１−メチルイミダゾール
化合物番号１６ ５−（２，４−ジメチルフェニル）メ
トキシ−１−メチルイミダゾール
化合物番号１７ ４−（２，６−ジメチルベンジル）−
１−ヒドロキシメチルイミダゾール
化合物番号１８ ５−（２，６−ジメチルベンジル）−
１−ヒドロキシメチルイミダゾール
化合物番号１９ ５−（２−メチルベンジル）−１−ヒ
ドロキシメチルイミダゾール
化合物番号２０ ５−（２，３−ジメチルベンジル）−
１−ヒドロキシメチルイミダゾール
化合物番号２１ ４−（２，６−ジメチルベンジル）−
１−（２−ヒドロキシエチル）イミダゾール
化合物番号２２ ５−（２，６−ジメチルベンジル）−
１−（２−ヒドロキシエチル）イミダゾール
化合物番号２３ ４−（２−メチルベンジル）−１−（
２−ヒドロキシエチル）イミダゾール
化合物番号２４ ４−（２，３−ジメチルベンジル）−
１−（２−ヒドロキシエチル）イミダゾール
化合物番号２５ ４−（２，６−ジメチルベンジル）−
１−（２−ヒドロキシプロピル）イミダゾール
化合物番号２６ ４−（２，６−ジメチルベンジル）−
１−（３−ヒドロキシプロピル）イミダゾール
化合物番号２７２−クロロ−４−（（２，６−ジメチル
フェニル）−（２−プロペノキシ）〕メチルイミダゾー
ル化合物番号２８２．訃ジクロロ−４−（（２，６−ジ
メチルフェニル）−（２−プロペノキシ）〕メチルイミ
ダゾール
化合物番号２９２−クロロ−４−（（２，６−ジメチル
フェニル）−（２−プロペノキシ）〕〕メチルー１−メ
チルイミダゾー
ル合物番号３０２−クロロ−５−（（２，６−ジメチル
フェニル）−（２−プロペノキシ）〕〕メチルー１−メ
チルイミダゾー
ル合物番号３１ ２．５−ジクロロ−４−（（２，６−
ジメチルフェニル）−（２−プロペノキシ）〕メチルイ
ミダゾール
化合物番号３２２．訃ジクロロ−４−（（２，６−ジメ
チルフェニル）メトキシコメチルイミダゾール化合物番
号３３ ２．５−ジクロロ−４−（（２，６−ジメチル
フェニル）メトキシコメチル−１−メチルイミダゾール
化合物番号３４ ２．４−ジクロロ−５−’ （（２，
６〜ジメチルフエニル）メトキシコメチル−１−メチル
イミダゾール
化合物番号３５ ４−（２，６−ジメチルベンジル）−
１−メルカプト−１−メチルイミダゾール
化合物番号３６ ５−（２，６−ジメチルベンジル）−
２−メルカプト−１−メチルイミダゾール
化合物番号３７ ５−（２−メチルベンジル）−２−メ
ルカプト−１−メチルイミダゾール
化合物番号３８ ５−（２，３−ジメチルベンジル）−
２−メルカプト−１−メチルイミダゾール
化合物番号３９ ４−（２，４−ジメチルベンジル）−
２−メルカプト−１−メチルイミダゾール
化合物番号４０ ５−（２，４−ジメチルベンジル）−
２−メルカプト−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に挙げる。Compound number 1 4-(2-(1,3-dioxolane-2
-yl)phenyl-hydroxycomethylimidazole compound number 2 4-(2-(1,3-dioxolane-2-
yl) phenyl-hydroxycomethyl-1-imidazole compound number 3 5-R2-(i,a-dioxolane-2
-yl)phenyl-hydroxycomethyl-1-imidazole compound number 4 5-(2-(1,3-dioxolane-2
-yl)phenyl-methoxycomethyl-1-imidazole Compound No. 54-(2-propienoxy-(2,6-dimethylphenoxy))methylimidazole Compound No. 6
4-(2-chloro-2-propienoxy)-(2,6-
2-methylphenoxy)] Methylimidazole Compound No. 74-(2-chloro-2-propienoxy)
-(2,6-dimethylfuunoxy)]]Methyl-1-methylimidazole compound number 85-(2-chloro-2-propienoxy)
-(2,6-dimethylphenoxy)]]Methyl-1-methylimidazole compound number 94-(2-chloro-2-propienoxy)
-(2-methylphenoxy)]methylimidazole compound number 105-(2-chloro-2-propienoxy)-
(2-Methylphenoxy)]]Methyl-1-methylimidazole' Compound No. 11 4-(2,6-Simethylphenyl)methoxy-1-methylimidazole Compound No. 12 5-(2,6-Simethylphenyl)methoxy-1-methylimidazole Compound No. 13 4-(2-methylphenyl)methoxy-methylimidazole Compound No. 14 5-(2-methylphenyl)methoxy-1-methylimidazole Compound No. 15 5-(2,3-dimethylphenyl)methoxy-1-methyl Imidazole compound number 16 5-(2,4-dimethylphenyl)methoxy-1-methylimidazole compound number 17 4-(2,6-dimethylbenzyl)-
1-Hydroxymethylimidazole compound number 18 5-(2,6-dimethylbenzyl)-
1-hydroxymethylimidazole compound number 19 5-(2-methylbenzyl)-1-hydroxymethylimidazole compound number 20 5-(2,3-dimethylbenzyl)-
1-Hydroxymethylimidazole compound number 21 4-(2,6-dimethylbenzyl)-
1-(2-hydroxyethyl)imidazole compound number 22 5-(2,6-dimethylbenzyl)-
1-(2-hydroxyethyl)imidazole compound number 23 4-(2-methylbenzyl)-1-(
2-Hydroxyethyl)imidazole Compound No. 24 4-(2,3-dimethylbenzyl)-
1-(2-hydroxyethyl)imidazole compound number 25 4-(2,6-dimethylbenzyl)-
1-(2-hydroxypropyl)imidazole compound number 26 4-(2,6-dimethylbenzyl)-
1-(3-Hydroxypropyl)imidazole Compound No. 272-chloro-4-((2,6-dimethylphenyl)-(2-propenoxy)]methylimidazole Compound No. 282. Dichloro-4-((2,6- Dimethylphenyl)-(2-propenoxy)]Methylimidazole Compound No. 292-chloro-4-((2,6-dimethylphenyl)-(2-propenoxy))]Methyl-1-methylimidazole Compound No. 302-chloro-5 -((2,6-dimethylphenyl)-(2-propenoxy)]]methyl-1-methylimidazole compound number 31 2.5-dichloro-4-((2,6-
Dimethylphenyl)-(2-propenoxy)]methylimidazole Compound No. 322. Dichloro-4-((2,6-dimethylphenyl)methoxycomethylimidazole Compound No. 33 2.5-dichloro-4-((2,6-dimethylphenyl)methoxycomethyl-1-methylimidazole Compound No. 34 2 .4-dichloro-5-' ((2,
6-dimethylphenyl)methoxycomethyl-1-methylimidazole Compound No. 35 4-(2,6-dimethylbenzyl)-
1-mercapto-1-methylimidazole compound number 36 5-(2,6-dimethylbenzyl)-
2-mercapto-1-methylimidazole compound number 37 5-(2-methylbenzyl)-2-mercapto-1-methylimidazole compound number 38 5-(2,3-dimethylbenzyl)-
2-mercapto-1-methylimidazole compound number 39 4-(2,4-dimethylbenzyl)-
2-mercapto-1-methylimidazole compound number 40 5-(2,4-dimethylbenzyl)-
2-Mercapto-1-methylimidazole Particularly preferred compounds of the present invention are listed below.
表 １
表 １ （つづき）
〔製造方法〕
一般式（１）で表わされる新規なベンジルイミダゾール
誘導体は次の反応式に従って製造することができる。Table 1 Table 1 (continued) [Production method] The novel benzylimidazole derivative represented by general formula (1) can be produced according to the following reaction formula.
＋１）Ｒ’がヒドロキシ基の場合は特開昭５６−３２４
６３などに記載された方法に従い製造することができる
。+1) When R' is a hydroxy group, JP-A-56-324
It can be manufactured according to the method described in 63 etc.
（２）Ｒ’がアルコキシ基の場合は化合物（ＩＶ）とア
ルコール（Ｒ’ＤＨ、Ｒ’はアルキル基である。）をｐ
−トルエンスルホン酸、硫酸などの酸存在下、トルエン
、ベンゼンなどの溶媒中、５０〜１８０℃、好ましくは
８０〜１５０℃で水を抜きながら反応させることによっ
て化合物（１）を得ることができる。(2) When R' is an alkoxy group, compound (IV) and alcohol (R'DH, R' is an alkyl group) are
Compound (1) can be obtained by reacting in the presence of an acid such as toluenesulfonic acid or sulfuric acid in a solvent such as toluene or benzene at 50 to 180°C, preferably 80 to 150°C while removing water.
（３）Ｒ’が水素原子の化合物（Ｖ）はハロゲン化アル
キルまたはアルデヒド類、オキシラン類と反応させるこ
とにより化合物（１）に導くことができる。(3) Compound (V) in which R' is a hydrogen atom can be led to compound (1) by reacting with an alkyl halide, aldehydes, or oxiranes.
（なお、化合物（Ｖ）には本発明の化合物が含まれる場
合がある。以下の化合物（Ｖｌ）も同じ。）（４）Ｒ２
が水素原子の化合物（ＶＩ）はアルキル金属と反応させ
た後、イオウと反応させ、次いで水素化アルミニウムリ
チウムなどの還元剤と反応させることによりＲ２がＳＮ
の化合物ＣＩ）に導くことができる。また、化合物（Ｖ
ｌ）はハロゲン分子またはＮ−ハロゲノフタル酸イミド
などハロゲン化剤と反応させることにより、Ｒ２がハロ
ゲン原子の化合物（１）に導くことができる。(Compound (V) may include the compound of the present invention. The same applies to the following compound (Vl).) (4) R2
The compound (VI) in which R2 is a hydrogen atom is reacted with an alkyl metal, then with sulfur, and then with a reducing agent such as lithium aluminum hydride, so that R2 becomes SN.
can lead to the compound CI). In addition, the compound (V
By reacting l) with a halogen molecule or a halogenating agent such as N-halogenophthalic acid imide, it can be led to compound (1) in which R2 is a halogen atom.
本発明の化合物のうち、上記に説明のない化合物も上記
方法に準じて製造することができる。Among the compounds of the present invention, compounds not described above can also be produced 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 explained with reference to Examples.
実施例１
２−（１，３−ジオキソラン−２−イル）−１−ブロモ
ベンゼン８．０ｇ（３４，９ｍｍｏｌ） 、マグネシウ
ム０．７ｇ（２８，８ｍｍｏｌ）にテトラヒドロフラン
（以下ＴＨＦと略す）１０−を加え、６５℃で１時間加
熱した。室温まで冷却後、４−ホルミルイミダゾール１
．３ｇ（１３，５ｍｍｏｌ）のｌＱｍｆｆｉＴＨＦ懸濁
液を加え、２時間加熱還流させた。反応混合物に水冷下
２Ｎ塩酸を中和するまで加え、クロロホルム抽出した。Example 1 Tetrahydrofuran (hereinafter abbreviated as THF) 10- was added to 8.0 g (34.9 mmol) of 2-(1,3-dioxolan-2-yl)-1-bromobenzene and 0.7 g (28.8 mmol) of magnesium. The mixture was then heated at 65° C. for 1 hour. After cooling to room temperature, 4-formylimidazole 1
．． 3 g (13.5 mmol) of lQmffiTHF suspension was added and the mixture was heated under reflux for 2 hours. 2N hydrochloric acid was added to the reaction mixture under water cooling until neutralization, and the mixture was extracted with chloroform.
水層に炭酸水素ナトリウムを加え、ｐＨを約１０にした
後、クロロホルム抽出した。クロロホルム層を無水硫酸
ナトリウムで乾燥した後、減圧上濃縮乾固し、目的物「
化合物番号１」を無色結晶として０．７ｇ（収率２１％
）得た。Sodium hydrogen carbonate was added to the aqueous layer to adjust the pH to approximately 10, followed by extraction with chloroform. After drying the chloroform layer with anhydrous sodium sulfate, it was concentrated to dryness under reduced pressure to obtain the desired product.
0.7 g of compound number 1 as colorless crystals (yield 21%)
)Obtained.
融点 １２５〜１３２℃
１Ｈ−核磁気共鳴スペクトル（重ジメチルスルホキシド
、δｐｐｍ ）
４．０〜４．２（ｍ、４Ｈ） 、６．０７（ｓ、 ＬＨ
） 、６．２３（ｓ、 ＩＨ） １６．６８（ｓ、ＩＨ
）、７．２〜７．８（ｍ、５Ｈ）実施例２
４− （（２，６−シメチルフエニル）−ヒドロキシコ
メチルイミダゾール３．０ｇ（１４，８ｍｍｏｌ） 、
２．３−ジクロロプロパツール２２．９ｇ（１７８ｍｍ
ｏｌ）、Ｐ−）ルエンスルホン酸１２．７ｇ（７３，８
ｍｍｏｌ）にベンゼン１６０−を加え、留出する水を抜
きながら２時間加熱還流させた。反応混合物を炭酸カリ
ウム水溶液で洗浄後、０、ｌｍｍＨｇ 、 １００℃で
濃縮乾固し、４− （（２，３−ジクロロプロポキシ）
−（２，６−シメチルフエニル）〕メチルイミダゾール
を無色油状物として４．３ｇ（収率９３％）得た。これ
をジメチルホルムアミド（以下ＤＭＦと略す）８０−に
溶解し、水素化ナトリウム０．３４ｇ（１４，２ｍｍｏ
ｌ）の３０ｍｌＤＭＦ懸濁液を室温で加え、１時間攪拌
した後、１００℃で２時間加熱した。Melting point 125-132°C 1H-nuclear magnetic resonance spectrum (deuterium dimethyl sulfoxide, δppm) 4.0-4.2 (m, 4H), 6.07 (s, LH)
), 6.23(s, IH) 16.68(s, IH
), 7.2-7.8 (m, 5H) Example 2 4-((2,6-dimethylphenyl)-hydroxycomethylimidazole 3.0 g (14.8 mmol),
2.3-dichloropropertool 22.9g (178mm
ol), P-) luenesulfonic acid 12.7 g (73,8
160 mmol of benzene was added to the mixture, and the mixture was heated under reflux for 2 hours while removing distilled water. After washing the reaction mixture with an aqueous potassium carbonate solution, it was concentrated to dryness at 0.1 mmHg and 100°C to give 4-((2,3-dichloropropoxy)
4.3 g (yield 93%) of -(2,6-dimethylphenyl)]methylimidazole was obtained as a colorless oil. This was dissolved in dimethylformamide (hereinafter abbreviated as DMF) 80-, and 0.34 g (14.2 mmol) of sodium hydride was added.
A suspension of 1) in 30 ml of DMF was added at room temperature, stirred for 1 hour, and then heated at 100°C for 2 hours.
反応混合物を減圧上濃縮乾固し、トルエンを加え、５％
水酸化ナトリウム水溶液で洗浄した。トルエン層を水洗
、無水硫酸ナトリウムで乾燥後、減圧下濃縮乾固し、目
的物「化合物番号６」を褐色結晶として３．８ｇ（収率
１００％）得た。The reaction mixture was concentrated to dryness under reduced pressure, and toluene was added to give a 5%
Washed with aqueous sodium hydroxide solution. The toluene layer was washed with water, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure to obtain 3.8 g (yield: 100%) of the target compound "Compound No. 6" as brown crystals.
１Ｈ−核磁気共鳴スペクトル（重クロロホルム。1H-Nuclear Magnetic Resonance Spectrum (Deuterochloroform.
δｐｐｍ ）
２．８８（ｓ、６Ｈ） 、３．９２（ｄ、Ｊ＝１４ＦＩ
ｚ、 ０１） 。δppm) 2.88 (s, 6H), 3.92 (d, J=14FI
z, 01).
４．１２（ｄ、Ｊ＝１４Ｈｚ、 ＩＨ） 、５．３６（
ｓ、 ＩＨ） 、５．５０（ｓ、 ＩＨ） 。4.12 (d, J=14Hz, IH), 5.36 (
s, IH), 5.50 (s, IH).
５．９８（ｓ、ＩＨ）、６．６０（ｓ、ＬＨ）、６．９
〜７．１（ｍ、３Ｈ）。5.98 (s, IH), 6.60 (s, LH), 6.9
~7.1 (m, 3H).
７．５０（ｓ、 ＩＨ）
実施例３
４− Ｄ２，６−シメチルフエニル）メトキシコメチル
イミダゾール０．７７ｇ（３，６ｍｍｏｌ）にピリジン
７−１無水酢酸７−、トリエチルアミン７−を加え２．
５時間加熱還流させた。反応混合物を減圧上濃縮乾固し
、アセトニトリル７−、ヨウ化メチル５．０ｇ（３５，
２ｍｍｏｌ）を加え室温で２日間攪拌した。この反応混
合物を減圧上濃縮し、トルエンを加え、炭酸水素ナトリ
ウム水溶液で洗浄した後、無水硫酸すトリウムで乾燥し
た。これを減圧上濃縮した後、減圧蒸留し、目的物「化
合物番号１１」を淡黄色液体として０．４ｇ （収率４
８％）得た。7.50 (s, IH) Example 3 Pyridine 7-1, acetic anhydride 7-, and triethylamine 7- were added to 0.77 g (3.6 mmol) of 4-D2,6-dimethylphenyl)methoxycomethylimidazole, and 2.
The mixture was heated under reflux for 5 hours. The reaction mixture was concentrated to dryness under reduced pressure, and acetonitrile 7-, methyl iodide 5.0 g (35,
2 mmol) was added thereto, and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure, toluene was added thereto, washed with an aqueous sodium bicarbonate solution, and then dried over anhydrous sodium sulfate. After concentrating this under reduced pressure, it was distilled under reduced pressure to obtain 0.4 g of the target compound "Compound No. 11" as a pale yellow liquid (yield: 4
8%).
沸点 １１５℃１０． ｌｍｍＨｇ ＋Ｈ−核磁気共鳴スペクトル（重クロロホルム。Boiling point 115℃10. lmmHg +H-Nuclear Magnetic Resonance Spectrum (Deuterochloroform.
δｐｐｍ ）
２．３２（ｓ、 ６）１） 、 ３．２８（ｓ、 ３１
（） 、 ３．７２（ｓ、 ３Ｈ） 、 ５．６６（ｓ
、 ＬＨ） 。δppm) 2.32(s, 6)1), 3.28(s, 31
(), 3.72(s, 3H), 5.66(s
, LH).
６．３０（ｓ、 ＩＨ） 、６．９〜７．２（ｍ、３Ｈ
） 、 ７．４５（ｓ、 ＩＨ）実施例４
４−（２，，６−シメチルベンジル）イミダゾール０．
７０ｇ（３，８ｍｍｏｌ）にトルエン１５−を加え、５
０℃でバラホルムアルデヒド０． ｌ１ｇ（３，７ｍｍ
ｏｌ）を添加した。6.30 (s, IH), 6.9-7.2 (m, 3H
), 7.45 (s, IH) Example 4 4-(2,,6-dimethylbenzyl)imidazole 0.
Add toluene 15- to 70 g (3.8 mmol),
Rose formaldehyde 0.0 at 0°C. l1g (3.7mm
ol) was added.
５０℃で１８．５時間加熱攪拌した後、減圧上濃縮し、
アセトンを加え、冷蔵庫内で２４時間放置した。生じた
結晶を濾過し、アセトン、エーテルで洗浄し、目的物「
化合物番号１８」を無色結晶として０．４２ｇ（収率４
９％）得た。After heating and stirring at 50°C for 18.5 hours, the mixture was concentrated under reduced pressure.
Acetone was added and left in the refrigerator for 24 hours. The resulting crystals are filtered and washed with acetone and ether to obtain the desired product.
0.42 g of compound number 18 as colorless crystals (yield: 4
9%) obtained.
融点 １３３〜１３９℃ ＋Ｈ−核磁気共鳴スペクトル（重クロロボルム。Melting point: 133-139℃ +H-Nuclear Magnetic Resonance Spectrum (Deuterochloroborum.
δｐｐｍ ）
２．２８（ｓ、 ６Ｈ） 、 ３．８６ （ｓ、 ２Ｈ
） 、 ５．０７（ｓ、 ２Ｈ） 、 ６．４４ （ｓ
、 ＩＨ） 。δppm) 2.28 (s, 6H), 3.86 (s, 2H
), 5.07(s, 2H), 6.44(s
, IH).
６．９〜７．１（ｍ、４Ｈ）
実施例５
４−（２，６−シメチルベンジル）イミダゾール１．８
６ｇ（１０ｍｍｏｌ）にＴＨＦ１５−を加え、室温で円
チレンオキシド０．５４ｄ （ｌｌｍｍｏｌ）の５ｍｆ
ｆ１ＴＨＦ溶液およびカリウム−ｔ−ブトキシド１．１
２ｇ（１０ｍｍｏｌ）を加え、１２時間攪拌した。反応
混合物にエタノール１゜−を加え０．５時間攪拌した後
、減圧上濃縮乾固した。これにクロロホルムを加え、不
溶物を濾別した後、濾液を濃縮し、シリカゲルクロマト
グラフィーで精製し、目的物「化合物番号２１」を無色
結晶として０．５３ｇ（収率２３％）得た。6.9-7.1 (m, 4H) Example 5 4-(2,6-dimethylbenzyl)imidazole 1.8
Add THF15- to 6g (10mmol), and add 5mf of 0.54d (llmmol) of cylene oxide at room temperature.
f1THF solution and potassium-t-butoxide 1.1
2 g (10 mmol) was added and stirred for 12 hours. After adding 1° of ethanol to the reaction mixture and stirring for 0.5 hours, the mixture was concentrated to dryness under reduced pressure. After adding chloroform and filtering off insoluble matter, the filtrate was concentrated and purified by silica gel chromatography to obtain 0.53 g (yield 23%) of the target compound "Compound No. 21" as colorless crystals.
融点 ９５〜９７℃ ＋Ｈ−核磁気共鳴スペクトル（重クロロホルム。Melting point: 95-97℃ +H-Nuclear Magnetic Resonance Spectrum (Deuterochloroform.
δｐｐＩＩ＋）
２．２０（ｓ、６Ｈ）、３．６〜３．８（ｍ、４Ｈ）
３．８２（ｓ、２Ｈ）。δppII+) 2.20 (s, 6H), 3.6-3.8 (m, 4H)
3.82 (s, 2H).
６、１８（ｓ、 ＬＨ） 、６．９６（ｓ、３Ｈ） 、
７．２５（ｓ、 ＩＨ）実施例６
実施例２と同様に４− （（２，６−シメチルフエニル
）−ヒドロキシコメチルイミダゾールとアリルアルコー
ルを反応させ、４− （（２，６−シメチルフエニル）
−（２−プロペノキシ）〕メチルイミダゾールを得た（
収率１００％）。この化合物０．５５ｇ（２，３ｍｍｏ
ｌ）をＴ ＨＦ １０ＴＲ１に溶解し、Ｎ−クロロフタ
ル酸イミド０．６１ｇ （４，６ｍｍｏｌ）を加え、室
温で２時間撹拌した。6, 18 (s, LH), 6.96 (s, 3H),
7.25(s, IH) Example 6 In the same manner as in Example 2, 4-((2,6-dimethylphenyl)-hydroxycomethylimidazole and allyl alcohol were reacted to form 4-((2,6-dimethylphenyl)
-(2-propenoxy)]methylimidazole was obtained (
yield 100%). 0.55 g (2,3 mmo) of this compound
1) was dissolved in THF 10TR1, 0.61 g (4.6 mmol) of N-chlorophthalic acid imide was added, and the mixture was stirred at room temperature for 2 hours.
反応混合物を減圧上濃縮した後、炭酸カリウム水溶液で
中和し、トルエンで抽出した。トルエン層を無水硫酸ナ
トリウムで乾燥した後、減圧上濃縮し、シリカゲルクロ
マトグラフィーで精製し、目約物「化合物番号３１」を
無色結晶として０．３４ｇ（収率４８％）得た。The reaction mixture was concentrated under reduced pressure, neutralized with an aqueous potassium carbonate solution, and extracted with toluene. The toluene layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel chromatography to obtain 0.34 g (yield: 48%) of a compound "Compound No. 31" as colorless crystals.
融点 ８３〜８５℃（塩酸塩） ＋Ｈ−核磁気共鳴スペクトル（重クロロホルム。Melting point: 83-85℃ (hydrochloride) +H-Nuclear Magnetic Resonance Spectrum (Deuterochloroform.
δｐｐｍ ）
２．２８（ｓ、６Ｈ）、５．０〜５．４（ｍ、２Ｈ）、
５．６〜６．３（ｍ、３８）。δppm) 2.28 (s, 6H), 5.0 to 5.4 (m, 2H),
5.6-6.3 (m, 38).
６．５５（ｓ、 ＩＨ） 、６．９〜７．１（ｎｒ、３
）り実施例７
５−（２，６−シメチルフエニル）−１−メチルイミダ
ゾール０．３７ｇ（１，９ｍｍｏｌ）をＴＨＦＩＯ−に
溶解し、０℃でｎ−ブチルリチウム（１４，５％ヘキサ
ン溶液）１．２ｍ （１’、８５ｎｃｍｏｌ ）を加え
、１５分間攪拌した後、イオウ粉末０．０６ｇ（１，９
ｍｍｏｌ）を加え、４時間加熱還流した。6.55 (s, IH), 6.9-7.1 (nr, 3
) Example 7 0.37 g (1.9 mmol) of 5-(2,6-dimethylphenyl)-1-methylimidazole was dissolved in THFIO-, and n-butyllithium (14.5% hexane solution) was dissolved at 0°C. After adding 0.2 m (1', 85 nmol) and stirring for 15 minutes, 0.06 g (1,9 nmol) of sulfur powder was added.
mmol) and heated under reflux for 4 hours.
反応混合物を水冷した後、水素化アルミニウムリチウム
０．０７ｇ（１，８ｍｍｏｌ）を加え、１時間加熱還流
した。再び氷冷した後、２Ｎ塩酸を加え、クロロホルム
抽出した。クロロホルム層を水洗、無水硫酸すトリウム
で乾燥後、減圧上濃縮乾固した。得られた固体をエタノ
ールから再結晶し、目的物「化合物番号３６」を淡褐色
結晶として０．１８ｇ（収率４２％）得た。After cooling the reaction mixture with water, 0.07 g (1.8 mmol) of lithium aluminum hydride was added, and the mixture was heated under reflux for 1 hour. After cooling on ice again, 2N hydrochloric acid was added and extracted with chloroform. The chloroform layer was washed with water, dried over anhydrous sodium sulfate, and then concentrated to dryness under reduced pressure. The obtained solid was recrystallized from ethanol to obtain 0.18 g (yield: 42%) of the target compound "Compound No. 36" as pale brown crystals.
融点 ２４４〜２４６℃ ＋Ｈ−核磁気共鳴スペクトル（重クロロホルム。Melting point: 244-246℃ +H-Nuclear Magnetic Resonance Spectrum (Deuterochloroform.
δｐｐｎ ）
２．２６（ｓ、６Ｈ） 、３．７０（ｓ、３Ｈ） 、３
．７４（ｓ、２Ｈ） 。δppn) 2.26 (s, 6H), 3.70 (s, 3H), 3
．． 74(s, 2H).
５．７８（ｓ、ＩＨ）、７．１０（ｓ、３０）〔作用お
よび効果〕
本発明の一般式（Ｎ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。5.78 (s, IH), 7.10 (s, 30) [Action and effect] The compound of the general formula (N) of the present invention and its acid addition salt have excellent anti-cerebral ischemic action and anti-hypobaric hypoxic action. and is useful as a brain function improving agent or an anti-amnestic agent, and also as a therapeutic agent for senile dementia.The compound according to the present invention may be administered alone, but if necessary or If desired, it can be administered orally or parenterally in various dosage forms.
坑１１１ｕＫ狡
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
後に話頭した。話頭後、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。Six ddY male mice weighing 22 to 30 g were used in each group. The test drug was administered intraperitoneally (i, p,), and 30 minutes after administration, the subject began speaking. After the onset of speech, the time until the head's gasping-like breathing ceased was measured, and the minimum dose that would significantly prolong this time was determined.
抗低圧他敗素跋験
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、）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 and anti-hyperopic experiments Groups of 7 to 10 ddY male mice weighing 23 to 28 g were used. 30 minutes after intraperitoneal (i, p) administration of the test drug,
The time from when the animal was placed in a desiccator and the pressure was reduced to 180 mmHg until death (survival time) was measured, and the minimum dose that would significantly prolong this time was determined.
結果を次表に示す。The results are shown in the table below.
Claims (1)
基で置換されていてもよい低級アルキル基であり、Ｒ＾
２は水素原子、低級アルキル基、フェニル基、ハロゲン
原子又はメルカプト基でありＲ＾３は水素原子、低級ア
ルキル基又はハロゲン原子であり、Ｒ＾４は低級アルキ
ル基、ハロゲン原子、ヒドロキシ基、エチレンジオキシ
メチル基、アミノ基又はニトロ基であり、Ｒ＾５は水素
原子、ヒドロキシ基又はアルコキシ基（該アルコキシ基
はハロゲン原子又はアルケニル基で置換されていてもよ
い。）であり、ｎは１ないし３の整数である。但し、Ｒ
＾１が水素原子または低級アルキル基であり、Ｒ＾２お
よびＲ＾３が共に水素原子であり、Ｒ＾５が水素原子又
はヒドロキシ基であり、かつＲ＾４が低級アルキル基で
あるものを除く。〕て表わされるベンジルイミダゾール
誘導体またはその薬学的に許容しうる塩類。(1) General formula [I] ▲Mathematical formulas, chemical formulas, tables, etc.▼[I] [In the formula, R^1 is a hydrogen atom or a lower alkyl group that may be substituted with a hydroxy group, R^
2 is a hydrogen atom, a lower alkyl group, a phenyl group, a halogen atom, or a mercapto group, R^3 is a hydrogen atom, a lower alkyl group, or a halogen atom, and R^4 is a lower alkyl group, a halogen atom, a hydroxyl group, or ethylene It is a dioxymethyl group, an amino group or a nitro group, R^5 is a hydrogen atom, a hydroxy group or an alkoxy group (the alkoxy group may be substituted with a halogen atom or an alkenyl group), and n is 1 An integer between 3 and 3. However, R
^1 is a hydrogen atom or a lower alkyl group, R^2 and R^3 are both hydrogen atoms, R^5 is a hydrogen atom or a hydroxy group, and R^4 is a lower alkyl group. except. ] A benzylimidazole derivative or a pharmaceutically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61294668A JPS63150266A (en) | 1986-12-12 | 1986-12-12 | Benzylimidazole derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61294668A JPS63150266A (en) | 1986-12-12 | 1986-12-12 | Benzylimidazole derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63150266A true JPS63150266A (en) | 1988-06-22 |
Family
ID=17810758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61294668A Pending JPS63150266A (en) | 1986-12-12 | 1986-12-12 | Benzylimidazole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63150266A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0552060A1 (en) * | 1992-01-16 | 1993-07-21 | Shionogi & Co., Ltd. | Imidazole derivatives having anti-HIV activity |
| WO1996010019A1 (en) * | 1994-09-26 | 1996-04-04 | Shionogi & Co., Ltd. | Imidazole derivative |
| US7141597B2 (en) * | 2003-09-12 | 2006-11-28 | Allergan, Inc. | Nonsedating α-2 agonists |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5632463A (en) * | 1979-08-07 | 1981-04-01 | Farmos Oy | Imidazole derivative* its manufacture and medicine as active component thereof |
| JPS57149273A (en) * | 1981-02-05 | 1982-09-14 | Farmos Oy | Imidazole derivative, manufacture and medicinal composition containing same as effective component |
-
1986
- 1986-12-12 JP JP61294668A patent/JPS63150266A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5632463A (en) * | 1979-08-07 | 1981-04-01 | Farmos Oy | Imidazole derivative* its manufacture and medicine as active component thereof |
| JPS57149273A (en) * | 1981-02-05 | 1982-09-14 | Farmos Oy | Imidazole derivative, manufacture and medicinal composition containing same as effective component |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0552060A1 (en) * | 1992-01-16 | 1993-07-21 | Shionogi & Co., Ltd. | Imidazole derivatives having anti-HIV activity |
| US5326780A (en) * | 1992-01-16 | 1994-07-05 | Shionogi & Co., Ltd. | Imidazole derivatives having anti-HIV activity |
| US5472965A (en) * | 1992-01-16 | 1995-12-05 | Shionogi & Co., Ltd. | Imidazole derivatives having anti-HIV activity |
| WO1996010019A1 (en) * | 1994-09-26 | 1996-04-04 | Shionogi & Co., Ltd. | Imidazole derivative |
| US5910506A (en) * | 1994-09-26 | 1999-06-08 | Shionogi & Co., Ltd. | Imidazole derivatives as anti-HIV agents |
| AU706095B2 (en) * | 1994-09-26 | 1999-06-10 | Shionogi & Co., Ltd. | Imidazole derivative |
| US6147097A (en) * | 1994-09-26 | 2000-11-14 | Shionogi & Co., Ltd. | Imidazole derivatives as anti-HIV agents |
| US7141597B2 (en) * | 2003-09-12 | 2006-11-28 | Allergan, Inc. | Nonsedating α-2 agonists |
| US7312238B2 (en) | 2003-09-12 | 2007-12-25 | Allergan, Inc. | Nonsedating α-2 agonists |
| US8022226B2 (en) | 2003-09-12 | 2011-09-20 | Allergan, Inc. | Nonsedating α-2 agonists |
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