JPS63198622A - Neutral muscle relaxant containing indole derivative - Google Patents
Neutral muscle relaxant containing indole derivativeInfo
- Publication number
- JPS63198622A JPS63198622A JP62030774A JP3077487A JPS63198622A JP S63198622 A JPS63198622 A JP S63198622A JP 62030774 A JP62030774 A JP 62030774A JP 3077487 A JP3077487 A JP 3077487A JP S63198622 A JPS63198622 A JP S63198622A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- lower alkyl
- hydrogen atom
- 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
- 150000002475 indoles Chemical class 0.000 title claims abstract description 8
- 239000003158 myorelaxant agent Substances 0.000 title claims description 7
- 230000007935 neutral effect Effects 0.000 title abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000002723 alicyclic group Chemical group 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 210000003205 muscle Anatomy 0.000 abstract description 8
- 230000002040 relaxant effect Effects 0.000 abstract description 5
- 206010019196 Head injury Diseases 0.000 abstract description 4
- 206010041349 Somnolence Diseases 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000002347 injection Methods 0.000 abstract description 2
- 239000007924 injection Substances 0.000 abstract description 2
- 239000006188 syrup Substances 0.000 abstract description 2
- 235000020357 syrup Nutrition 0.000 abstract description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 2
- 206010062575 Muscle contracture Diseases 0.000 abstract 1
- 208000032140 Sleepiness Diseases 0.000 abstract 1
- 208000006111 contracture Diseases 0.000 abstract 1
- 230000037321 sleepiness Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 24
- -1 alicyclic amine Chemical class 0.000 description 19
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- SQUNAWUMZGQQJD-UHFFFAOYSA-N 1-(4-ethylphenyl)-2-methyl-3-(piperidin-1-yl)propan-1-one Chemical compound C1=CC(CC)=CC=C1C(=O)C(C)CN1CCCCC1 SQUNAWUMZGQQJD-UHFFFAOYSA-N 0.000 description 8
- 229960002565 eperisone Drugs 0.000 description 8
- 206010002091 Anaesthesia Diseases 0.000 description 7
- 230000037005 anaesthesia Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- DAITVOCMWPNFTL-UHFFFAOYSA-N 5-methyl-1h-indole-2-carboxylic acid Chemical compound CC1=CC=C2NC(C(O)=O)=CC2=C1 DAITVOCMWPNFTL-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 208000009881 Decerebrate State Diseases 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 3
- 239000002253 acid Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000001198 duodenum Anatomy 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- BYJQAPYDPPKJGH-UHFFFAOYSA-N 3-(2-carboxyethyl)-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2C(CCC(=O)O)=C(C(O)=O)NC2=C1 BYJQAPYDPPKJGH-UHFFFAOYSA-N 0.000 description 2
- OUDKEPMYUAFKLL-UHFFFAOYSA-N 3-nitro-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2C([N+]([O-])=O)=C(C(=O)O)NC2=C1 OUDKEPMYUAFKLL-UHFFFAOYSA-N 0.000 description 2
- FUQOTYRCMBZFOL-UHFFFAOYSA-N 5-chloro-1H-indole-2-carboxylic acid Chemical compound ClC1=CC=C2NC(C(=O)O)=CC2=C1 FUQOTYRCMBZFOL-UHFFFAOYSA-N 0.000 description 2
- YEBJVSLNUMZXRJ-UHFFFAOYSA-N 5-methoxyindole-2-carboxylic acid Chemical compound COC1=CC=C2NC(C(O)=O)=CC2=C1 YEBJVSLNUMZXRJ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000008238 Muscle Spasticity Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- WQJFIWXYPKYBTO-UHFFFAOYSA-N indole-1-acetic acid Chemical compound C1=CC=C2N(CC(=O)O)C=CC2=C1 WQJFIWXYPKYBTO-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 231100000053 low toxicity Toxicity 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
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- PNBRACSSFLTMRS-UHFFFAOYSA-N 1-propan-2-yl-2-propylhydrazine Chemical compound CCCNNC(C)C PNBRACSSFLTMRS-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
- ZIEMPQWRHBEBOT-UHFFFAOYSA-N 2-indol-1-yl-n-methylacetamide Chemical compound C1=CC=C2N(CC(=O)NC)C=CC2=C1 ZIEMPQWRHBEBOT-UHFFFAOYSA-N 0.000 description 1
- IUUZMSMGSOUFTO-UHFFFAOYSA-N 2-indol-1-ylacetamide Chemical compound C1=CC=C2N(CC(=O)N)C=CC2=C1 IUUZMSMGSOUFTO-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- 206010049816 Muscle tightness Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010041415 Spastic paralysis Diseases 0.000 description 1
- 206010057268 Spinal cord paralysis Diseases 0.000 description 1
- 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
- 208000028994 Spinal vascular disease Diseases 0.000 description 1
- 206010058009 Subacute myelo-opticoneuropathy Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000001841 basilar artery Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 208000025434 cerebellar degeneration Diseases 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000009189 diving Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- HZYWFQBABNUAAP-UHFFFAOYSA-N gold;hydrochloride Chemical compound Cl.[Au] HZYWFQBABNUAAP-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002940 repellent Effects 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 210000004189 reticular formation Anatomy 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- DVQHRBFGRZHMSR-UHFFFAOYSA-N sodium methyl 2,2-dimethyl-4,6-dioxo-5-(N-prop-2-enoxy-C-propylcarbonimidoyl)cyclohexane-1-carboxylate Chemical compound [Na+].C=CCON=C(CCC)[C-]1C(=O)CC(C)(C)C(C(=O)OC)C1=O DVQHRBFGRZHMSR-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 208000005801 spondylosis Diseases 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 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
- QEXALZRNBZDFCB-UHFFFAOYSA-N tert-butyl hypofluorite Chemical compound CC(C)(C)OF QEXALZRNBZDFCB-UHFFFAOYSA-N 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 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
- 230000001052 transient effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は後記一般式（１）で表わされるインドール誘導
体を有効成分として含有する中枢性筋弛緩剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a central muscle relaxant containing an indole derivative represented by the general formula (1) below as an active ingredient.
脳卒中等の脳循環障害の後遺症、あるい（工頭部外傷の
後遺症として、しばしば筋の強硬又は痙縮を発症し、リ
ービリテーションを困難にしている、このために、これ
らの筋強硬又は痙縮を緩解する、眠気を伴なわない中枢
性筋弛緩剤の開発が望まれている。Muscle rigidity or spasticity often develops as a sequela of cerebral circulation disorders such as stroke, or after-effects of head trauma, making rehabilitation difficult. There is a desire to develop a central muscle relaxant that does not cause drowsiness.
本発明者らは、このような目的に沿った化学物質の探索
過程の中から、一般式（Ｉｎ有するインＰ−ル誘導体が
強い中枢性筋弛緩作用をもつことを発見し、中枢性筋弛
緩剤として有用であることを確認して本発明を完成する
に至った。In the process of searching for chemical substances for these purposes, the present inventors discovered that an inP-le derivative having the general formula (In) has a strong central muscle relaxing effect. The present invention was completed after confirming that it is useful as a drug.
本発明の新規な中枢性筋弛緩剤は
一般式
基を示し、Ｒ６は水素原子または低級アルキル基を示し
、Ｙは水酸基、低級アルコキシ基、アミン基、モノ若し
くはジ低級アルキルアミノ基または脂環状アミン基を示
す。）を示し、Ｒ２は水素原子、低級アルキル基、−ロ
ゲン原子または式−〇〇Ｚ基（式中、２は水酸基、低級
アルコキシ基、アミン基、モノ若しくは）低級アルキル
アミノ基または脂環状アミノ基を示す。）全示し、Ｒ３
は水素原子、カルボキシ基で置換されていてもよい低級
アルキル基、−ロゲン原子またはニトロ基金示し、Ｒ４
は水素原子、低級アルキル基、低級アルコキシ基、ハロ
ゲン原子、水酸基、アミン基、モノ若しくはジ低級アル
キルアミノ基、カルボキシ基または低級アルコキシ力ｋ
＆ ： ルキル基またはハロゲン原子を表わす。〕を
有するインＰ−ル誘導体またはその薬理上許容される塩
を有効成分とする。The novel central muscle relaxant of the present invention represents a general formula group, R6 represents a hydrogen atom or a lower alkyl group, and Y represents a hydroxyl group, a lower alkoxy group, an amine group, a mono- or di-lower alkylamino group, or an alicyclic amine. Indicates the group. ), R2 is a hydrogen atom, a lower alkyl group, a -rogen atom, or a group of the formula -〇〇Z (wherein 2 is a hydroxyl group, a lower alkoxy group, an amine group, a mono- or lower alkylamino group, or an alicyclic amino group) shows. ) all shown, R3
represents a hydrogen atom, a lower alkyl group optionally substituted with a carboxy group, a -rogen atom or a nitro group, R4
is a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, a hydroxyl group, an amine group, a mono- or di-lower alkylamino group, a carboxy group, or a lower alkoxy group.
&: Represents an alkyl group or a halogen atom. ] or a pharmacologically acceptable salt thereof as an active ingredient.
本発明において用いられる好適な化合物としメチル、エ
チル、プロピル、イソプロピル、ブチル、イソブチル、
式−ブチルのような直鎖状若しくは有枝鎖状の炭素数１
乃至４個を有するアルキル基または芳香環にメチル、エ
チル、プロピル、イソプロピルのような炭素数１乃至３
個を有するアルキル基、メトキシ、エトキシ、プロポキ
ン、イソプロポキシのような炭素数１乃至３個を有する
アルコキシ基またはフッ素、塩素、臭素のＬうな−・ロ
ゲン原子を有するか有しないフェニルなどのアリール基
金示し、Ｒ６は水素原子または前述しりＲ５と同意義含
有するアルキル基を示し、Ｙは水酸基、メトキシ、エト
キシ、プロポキシ、イソプロポキシ、ブトキシ、インブ
トキシ、ｔａｒｔ−シトキシのような直鎖状若しくは有
枝鎖状の炭素数１乃至４個を有するアルコキン基、アミ
ン基、メチルアミン、エチルアミノ、プロピルアミノ、
インプロピルアミノ、ブチルアミノ、インブチルアミノ
、ジメチルアミノ、ジメチルアミノ、ジプロピルアミノ
のような炭素数１乃至６個金有するモノ若しくはシアル
キルアミノ基または１−ピロリジニル、ピペリジノ、モ
ルホリノ、１−ピペラジニル、４−メチル−１−ピペラ
ジニルのような５乃至６員脂環状アミノ基を示す。）を
示し、Ｒ２は水素原子、メチル、エチル、プロピル、イ
ソプロピル、ブチル、インブチル、式−ブチル、ｔａｒ
ｔ−ブチルの工うな直鎖状若しくは有枝鎖状の炭素数１
乃至４個を有するアルキル基、フッ素、塩素、臭素のよ
うなハロゲン原子または式−〇〇Ｚ基（式中、２は前述
したＹと同意義を有する水酸基、アルコキシ基、アミノ
基、モノ若しくにジアルキルアミノ基または脂環状アミ
ン基を示す。）ｔ−示し、Ｒ５は水素原子、メチル、エ
チル、プロピル、イソプロピル、ブチル、イソブチル、
ｔａｒｔ−ブチル、カルボキシメチル、２−カルボキシ
エチル、３−カルボキシプロピルのようなカルぜキシ基
で置換されていてもよい炭素数１乃至４個を有するアル
キル基、フッ素、塩素、臭素のようなハロゲン原子また
はニトロ基を示し Ｈ４は水素原子、メチル、エチル、
プロピル、イソプロピル、ブチル、インブチル、式−ブ
チル、ｔａｒｔ−ブチルのような直鎖状若しくは有枝鎖
状の炭素数１乃至４個を有するアルキル基、メトキシ、
エトキシ、プロポキシ、イソプロポキシ、ブトキシ、イ
ソシトキシ、（８）−ブトキシ、ｔａｒ ｔ−ブトキシ
のような直鎖状若しくは有枝鎖状の炭素数１乃至４個を
有するアルコキシ基、フッ素、塩素、臭素のよりな一ロ
ゲン原子、水酸基、アミノ基、メチルアミノ、エテルア
ミノ、プロピルアミノ、イソプロピルアミン、ブチルア
ミノ、イソブチルアミノ、ジメチルアミノ、ジエチルア
ミノ、ジプロピルアミノのような炭素数１乃至６個を有
するモノ若しくはノアルキルアミノ基、カルブキシ基ま
たはメトキシカルビニル、エトキシカルボニル、プロポ
キシカルゲニル、インプロポキシカルボニル、ブトキシ
カルゼニル、イソブトキシカル−ニルのような炭素数２
乃至５個を有するアルコキシカルボニル基金示し、置換
基Ｒ１とＲ２との相互関係が前述した条件を満たすもの
があげられる。Preferred compounds used in the present invention include methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
Formula - linear or branched chain with 1 carbon number, such as butyl
An alkyl group having 1 to 4 carbon atoms or an aromatic ring having 1 to 3 carbon atoms such as methyl, ethyl, propyl, isopropyl
an alkyl group having 1 to 3 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy; or an aryl group, such as phenyl, with or without a fluorine, chlorine, or bromine atom; R6 represents a hydrogen atom or an alkyl group having the same meaning as the above-mentioned R5, and Y represents a hydroxyl group, a linear or branched group such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, imbutoxy, tart-cytoxy. Alcoquine group having 1 to 4 chain carbon atoms, amine group, methylamine, ethylamino, propylamino,
Mono- or sialkylamino groups having 1 to 6 carbon atoms such as inpropylamino, butylamino, imbutylamino, dimethylamino, dimethylamino, dipropylamino, or 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, It represents a 5- to 6-membered alicyclic amino group such as 4-methyl-1-piperazinyl. ), R2 is a hydrogen atom, methyl, ethyl, propyl, isopropyl, butyl, inbutyl, butyl, tar
Straight chain or branched chain carbon number 1 of t-butyl
an alkyl group having 4 to 4 atoms, a halogen atom such as fluorine, chlorine, or bromine, or a group of the formula -〇〇Z (wherein 2 is a hydroxyl group, alkoxy group, amino group, mono or represents a dialkylamino group or an alicyclic amine group.) t- represents a hydrogen atom, methyl, ethyl, propyl, isopropyl, butyl, isobutyl,
an alkyl group having 1 to 4 carbon atoms which may be substituted with a carboxy group such as tart-butyl, carboxymethyl, 2-carboxyethyl, and 3-carboxypropyl; a halogen such as fluorine, chlorine, and bromine; Represents an atom or nitro group, H4 is a hydrogen atom, methyl, ethyl,
A linear or branched alkyl group having 1 to 4 carbon atoms such as propyl, isopropyl, butyl, inbutyl, formula-butyl, tart-butyl, methoxy,
Linear or branched alkoxy groups having 1 to 4 carbon atoms such as ethoxy, propoxy, isopropoxy, butoxy, isocytoxy, (8)-butoxy, tar t-butoxy, fluorine, chlorine, bromine, etc. Mono- or carbon atoms having 1 to 6 carbon atoms, such as monologen atoms, hydroxyl groups, amino groups, methylamino, etelamino, propylamino, isopropylamine, butylamino, isobutylamino, dimethylamino, diethylamino, and dipropylamino. Alkylamino group, carboxy group or 2 carbon atoms such as methoxycarbinyl, ethoxycarbonyl, propoxycargenyl, impropoxycarbonyl, butoxycarzenyl, isobutoxycargenyl
Examples include alkoxycarbonyl radicals having 5 to 5 alkoxycarbonyl groups, and the mutual relationship between substituents R1 and R2 satisfies the above-mentioned conditions.
さらに、前記一般式（Ｉｎ有するインドール誘導体の好
適化合物として、以下の化合物を例示することができる
。Further, as suitable compounds for the indole derivative having the general formula (In), the following compounds can be exemplified.
（１）インドール−２−カルボン酸
（２）３−クロルインＰ−ルー２−カル？ン酸（３）
３−ニトロインドール−２−カルボン酸（４） ５
−クロルインドール−２−カルボン酸（５） ５−メ
チルインドール−２−カルボン酸（６） ５−メトキ
シインドール−２−カルボン酸（７）７−メドキシイン
ドールー２−カルボン酸（８） ３−β−カルボキシ
エチルインドール−２−カルボン酸
（９）インドール−１−酢酸
α０ インＰ−ルー１−酢醗アミド
α℃ インドール−１−酢酸メチルアミド（６） イン
ｒ−ルー１−酢酸４＼ノプロヒ０ルアミド前記一般式（
１１を有するインドール誘導体の薬理上許容される塩は
、例えばカルボン酸金属塩としてナトリウム塩、カリウ
ム塩、マグネシウム塩、カルシウム塩のようなアルカリ
金属およびアルカリ土類金属の塩、アルミニウム塩など
があげられ、アミンの酸付加塩として塩酸塩、臭化水素
酸塩、硫酸塩のような鉱酸塩、シュウ酸塩、乳酸塩、ク
エン酸塩、酒石酸塩、コーク酸塩、マレイン酸塩、メタ
ンスルホン酸塩のような有機酸塩など金あげることがで
きる。(1) Indole-2-carboxylic acid (2) 3-chloroin P-ru-2-cal? acid (3)
3-nitroindole-2-carboxylic acid (4) 5
-Chlorindole-2-carboxylic acid (5) 5-methylindole-2-carboxylic acid (6) 5-methoxyindole-2-carboxylic acid (7) 7-medoxyindole-2-carboxylic acid (8) 3- β-Carboxyethyl indole-2-carboxylic acid (9) Indole-1-acetic acid α0 Indole-1-acetic acid amide α℃ Indole-1-acetic acid methylamide (6) Indole-1-acetic acid 4＼Noprohyde 0 General formula (
Examples of pharmacologically acceptable salts of indole derivatives having 11 include carboxylic acid metal salts such as alkali metal and alkaline earth metal salts such as sodium salts, potassium salts, magnesium salts, and calcium salts, and aluminum salts. , mineral acid salts like hydrochloride, hydrobromide, sulfate, oxalate, lactate, citrate, tartrate, cochlorate, maleate, methanesulfonic acid as acid addition salts of amines. Organic acid salts such as salts can be used.
本発明の有効成分である一般式ｍｔ有するインドール誘
導体は、公知の化合物であり、文献記載の方法に従って
製造される。例えば化合物（１）および（２）は、Ｂｅ
ｒ、 ５６ Ｂ 、 １０２４〜１０３６（１９２３）
に、ま１こ化合物α０は、Ｊ、 Ｍｅｄ、 Ｃｈｅｍ、
２０ 、５３７−５４０（１９７７）に記載されてい
る方法に従ってつくられる。The indole derivative having the general formula mt, which is the active ingredient of the present invention, is a known compound and is produced according to methods described in literature. For example, compounds (1) and (2) are Be
r, 56 B, 1024-1036 (1923)
The compound α0 is described in J, Med, Chem,
20, 537-540 (1977).
本発明の前記一般式（１） ’＆有する化合物は、薬理
試験および毒性試験によれば、優れた中枢性筋弛緩作用
を示し、しかも毒性の低い化合物であるが、以下にそれ
らの試験について具体的に説明する。According to pharmacological and toxicological tests, the compound of the present invention having the general formula (1) '& shows an excellent central muscle relaxing effect and is a compound with low toxicity. Explain in detail.
方法：ラットを一ロセン麻酔下に脳定位固定装置（ｓＲ
−ｓ、成茂）上に固定した上、中脳網様体（ＡＰ：０．
Ｌ：±１．５ 、 Ｈ： −３，０）に、直径０．７ｆ
ｌで先端１正以外を絶縁した電極をＰｅｌｌｅｇｒｉｎ
ｏらの脳地図（Ｌ、Ｊ 、 Ｐｅｌ’ｌｅｇｒｉｎｏ、
Ａ、Ｓ、 Ｐｅｌｌｅｇｉｒｉｎｏ ａｎｄＡ、Ｊ
、Ｃｕｓｂｍａｎ ： Ａ ５ｔｅｒｅｏｔａｘｉｃ
Ａｔ１ａｓ ｏｆ ｔｈｅ ＲａｔＢｒａｉｎ、
Ｐｌｅｎｕｍ Ｐｒｅｓｓ、 Ｎｅｗ Ｙｏｒｋ ａ
ｎｄ Ｌｏｎｄｏｎ（１９６７） 〕に従って両側性に
挿入した。この電極を介してリージョン ジェネレータ
ー（グラス社Ｍ、ＬＭ４Ａ）から高周波（１００ｋＨｚ
、１０〜２０ｍＡ） の電流を２〜３分間流し、この
部位を電気的に焼灼した。Method: Rats were placed in a stereotaxic apparatus (sR) under monolocene anesthesia.
-s, Narishige) and the midbrain reticular formation (AP: 0.
L: ±1.5, H: -3,0), diameter 0.7f
Pellegrin the electrode insulated except for the tip 1 with l
Brain map of o et al. (L, J, Pel'legrino,
A, S, Pellegirino and A, J
,Cusbman: A5tereotaxic
At1as of the RatBrain,
Plenum Press, New York a
nd London (1967)]. A high frequency (100kHz
, 10-20 mA) for 2-3 minutes to electrically cauterize the site.
なお、この時の不関電極として頭皮内膜にクリップをは
さんで用いた。その後直ちに動物を脳定位固定装置から
はずし、十二指腸内にポリエチレン製カニユーレ（Ｆｒ
、３）を挿入し、接着剤で固定した。これらの手術が終
了し１このち、厘ちに一ロセン麻酔を停止し、１．５時
間経過して動物が麻酔から覚醒するのを待って、自家製
の後肢固定装置上に固定し１こ、動物の両側後肢足首前
部の付根を固定したうえ、両側足前部を１分間に６秒間
、４ｆｌの長さだけ押し、その除虫ずる反発カーｉ Ｆ
Ｄビック・アップ（日本光電）を介してポリグラフ上に
描記した。Note that a clip was used as an indifferent electrode at this time by inserting it into the scalp lining. Thereafter, the animal was immediately removed from the stereotaxic apparatus, and a polyethylene cannula (Fr) was inserted into the duodenum.
, 3) was inserted and fixed with adhesive. Immediately after these surgeries were completed, the 1-Locene anesthesia was stopped, and after 1.5 hours the animal woke up from anesthesia, it was fixed on a homemade hindlimb fixation device. After fixing the bases of the front ankles of both hind legs of the animal, the front parts of both hind legs were pressed by a length of 4 fl for 6 seconds per minute, and the repellent car was used to remove insects.
It was drawn on a polygraph using D Big Up (Nihon Kohden).
被検化合物ｉ ０．５１ ＣＭＣ溶液に懸濁し、予め挿
入しておいたカニユーレを介して十二指腸内（ｉ、ｄ、
）または胃内（ｐ−ｏ、）に投与した。Test compound i 0.51 Suspended in CMC solution and injected into the duodenum (i, d,
) or intragastrically (po, ).
成績：成績を第１表にまとめた。Results: The results are summarized in Table 1.
第１表 ラット除脳固縮に対する抑制作用（１）
３０〜勺ＣＩ）−０−） ５０チ ６０分（２
） ５０φ（ｉ、’ｄ、） ２５チ ４０
分（Ｌｏ ５０１ｖＫｆ（ｐ、ｏ、） ７０％
＞９０分（対照化合物）
塩酸エペリゾン ３０’％’麺（ｐ、ｏ−） ３
０チ ４５分治療剤として既に臨床上用いられ
ている塩酸エペリゾンと同等又はそれ以上にラットの除
脳固縮を緩解させることが明らかにされた。Table 1 Inhibitory effect on rat decerebrate rigidity (1)
30～庺CI)-0-) 50chi 60min(2
) 50φ(i,'d,) 25chi 40
Minutes (Lo 501vKf(p, o,) 70%
>90 minutes (control compound) Eperisone hydrochloride 30'%' noodles (p, o-) 3
It has been shown that this drug alleviates decerebrate rigidity in rats as much as or better than eperisone hydrochloride, which has already been clinically used as a 45-minute therapeutic agent.
２、 ネコの貧血性除脳固縮緩解作用
方法：ネコをエーテル麻酔下に脳定位固定装置上に固定
、気管カニユーレを装着した。次いで両側総頚動脈なら
びに脳底動脈を結紮して完状筋から筋電図を導出し、積
分計を介してベン書きレコーダー上に描記した。2. Method for resolving anemic decerebrate rigidity in cats: The cat was fixed on a stereotaxic apparatus under ether anesthesia, and a tracheal cannula was attached. Next, both common carotid arteries and basilar arteries were ligated, and an electromyogram was derived from the muscle perfectus and was recorded on a Ben recorder via an integrator.
また、股静脈から常時血圧全モニターし、自発性呼吸と
ともに積分された筋放電と同時に記録した。なお、動物
の体温上３７−３９℃に常に維持し、被検化合物を予め
挿入したカテーテル金倉して十二指腸内に投与した。In addition, total blood pressure was constantly monitored from the femoral vein, and spontaneous respiration and integrated muscle discharge were recorded simultaneously. The animal's body temperature was always maintained at 37-39°C, and the test compound was administered into the duodenum through a catheter inserted in advance.
成績：インｔ−ルー２−カルボン酸（化合物（１））を
３０■／Ｋｆ投与すると、投与後１０分には、積分され
た筋放電は投与前の約３０％に減少し投与後２０分には
完全に抑制され、この状態が約３〜４時間、又はそれ以
上持続し１こ。この間投与直後に、一過性に心拍数が増
加した以外、血圧および自発性呼吸に特記すべき影響を
認めなかった。Results: When int-2-carboxylic acid (compound (1)) was administered at 30 μ/Kf, the integrated muscle discharge decreased to approximately 30% of the pre-administration level at 10 minutes after administration, and 20 minutes after administration. The condition is completely suppressed and lasts for about 3 to 4 hours or more. During this period, no notable effects on blood pressure or spontaneous respiration were observed, other than a transient increase in heart rate immediately after administration.
即ち、化合物（１）は、ラットのみでなく、ネコでも、
痙縮のモデルである除脳固１Ｉｉ７Ａｔ−抑制する作用
含水すことが明らかにされた。このことは、化合物（１
）の中枢性筋弛緩作用がラットに限定されるものではな
いことを意味している。That is, compound (1) is effective not only in rats but also in cats.
It was revealed that decerebrate 1Ii7At, a model of spasticity, has an inhibitory effect on water content. This means that the compound (1
This means that the central muscle relaxant effect of ) is not limited to rats.
方法＝１群５〜７匹のＤＤＹ系雄性成熟マウス（体！２
０〜３０ ｆ ） ？使用した。マウスに被検化合物（
０，５％ ＣＭＣ溶液に懸濁）を経口的に投与した１時
間後（塩酸エペリゾンは作用の持続時間が短いので５〜
１５分後）に、チオベンタール（３０ｍ９／Ｋｇ） ’
（ｒ尾静脈から注射し、マウスの正向反射が回復するま
での時間を計測した。Method = 5 to 7 DDY male adult mice per group (body!2
0~30f)? used. Test compound (
1 hour after orally administering 0.5% CMC solution (suspended in CMC solution) (eperisone hydrochloride has a short duration of action, so
15 minutes later), thiobental (30m9/Kg)'
(r) was injected through the tail vein, and the time until the righting reflex of the mouse recovered was measured.
成績：成績を第２表にまとめた。Results: The results are summarized in Table 2.
第２表 チオベンタール麻酔時間におよぼす影響化合物
番号 用−ｔＣηＡ） 投与経路 動物数麻酔時間（
秒〕（２） ０ ６２
４３・７±２７・６５０ １、ｐ、 １０
３０６．９±３１．６αＯＯ８２４３・６±２０・２
５０ ｐ、ｏ、 ７ ３９７．６±１
１３．４（対照化合物）
塩酸エペリゾン ０ １０ ２０
６±１３．１１０ ｐ、０．５ １８２±
９．８３０ ５ １９２±１８，３
１００ ５ ２４７±３４，９即ち
、化合物（２）およびαＯは、脳循環障害治療剤として
既に臨床上使用されている塩酸エペリゾンと同様に、チ
オベンタール麻酔時間を延長しなかった。このことは、
化合物（２）およびαＱは、塩酸エペリゾンと同様に眠
気を催し難い化合物であることを意味している。Table 2 Effect of thiobental on anesthesia time Compound number -tCηA) Administration route Number of animals Anesthesia time (
seconds〕(2) 0 62
43.7±27.650 1, p, 10
306.9±31.6αOO8243・6±20・2 50 p, o, 7 397.6±1
13.4 (control compound) Eperisone hydrochloride 0 10 20
6±13.110 p, 0.5 182±
9.830 5 192±18,3
100 5 247±34,9 That is, compound (2) and αO did not prolong the thiobental anesthesia time, similar to eperisone hydrochloride, which has already been used clinically as a therapeutic agent for cerebral circulation disorder. This means that
Compound (2) and αQ mean that, like eperisone hydrochloride, they are compounds that do not easily cause drowsiness.
４、急性毒性
化合物０ｑおよび塩酸エペリゾン金１群１０匹のマウス
に１００，３００および１０００Ｔｎ？Ａ経口投与し、
５日間の観察をした。その結果、化合物叫では検討した
すべての用量において、金側生存したが、塩酸エペリゾ
ン投与群では、３００■／Ｋｆで２７１０例、１００Ｏ
Ｗ／Ｋｇでは金側死亡した。このことは、化合物αＱは
、既に臨床上使用されている塩酸エペリゾンより急性毒
性が低い化合物であることを意味している。4. Acutely toxic compound 0q and eperisone gold hydrochloride 100,300 and 1000Tn to 1 group of 10 mice? A Orally administered;
Observations were made for 5 days. As a result, in the case of the compound, 2,710 patients survived at 300 μ/Kf, and 2,710 patients survived at 100 O
In W/Kg, the gold side died. This means that compound αQ is a compound with lower acute toxicity than eperisone hydrochloride, which is already in clinical use.
以上説明したように、前記一般式ＣＩ） を有する化合
物は、眠気を誘発することなく、極めて低毒性で且つ中
枢性筋弛緩作用を有し、経口投与または十二指腸内ある
いは腹腔内投与法によってもすみやかに吸収されて、作
用を発現するに至るものである。上記の動物実験から、
臨床的には経口投与が可能であるが、特に中枢性筋弛緩
剤として、脳卒中後遺症および頭部外傷性後遺症に有用
である。さらにまた、痙性背髄麻痺、頚部背椎症術後後
遺症（脳背髄腫瘍を含む）、外傷後遺症〔背髄損傷、頭
部外傷〕、筋萎縮性側索硬化症、脳性小児麻痺、背髄小
脳変性症、背髄血管障害、スモン（５Ｍ０Ｎ ）、潜水
病、その他の脳背髄疾患による痙性麻痺および全身こむ
ら返り病ならびに肩こり等の筋緊張先進にも有用である
。その形態としては、例えば錠剤、カプセル剤、顆粒剤
、散剤、シロップ剤などによる経口投与方法、注射剤、
半開などによる非経口投与法があげられる。これらの各
種製剤は、常法に従って目的に応じて生薬に賦形剤、結
合剤、崩壊剤、滑沢剤、矯味剤など医薬の製剤技術分野
において通常使用しうる既知の補助剤を用いて製剤化す
ることができる。その使用１−ｔＸ症状、年令、体重等
によって異なるが、経口投与の場合、通常は底入に対し
、１回５ｑ乃至５０ｑｔ＝１日１乃至３回投与すること
ができる。As explained above, the compound having the general formula CI) does not induce drowsiness, has extremely low toxicity, has a central muscle relaxing effect, and can be administered orally, intraduodenumally, or intraperitoneally. It is absorbed by the body and develops its effects. From the above animal experiments,
Clinically, it can be administered orally, and is particularly useful as a central muscle relaxant for the aftereffects of stroke and head trauma. Furthermore, spastic dorsal spinal cord paralysis, cervical dorsal spondylosis postoperative sequelae (including cerebrospinal cord tumors), trauma sequelae [dorsal spinal cord injury, head trauma], amyotrophic lateral sclerosis, cerebral palsy, dorsal spinal cord It is also useful for developing muscle tension such as cerebellar degeneration, dorsal spinal vascular disease, SMON (5M0N), diving disease, and other cerebrospinal diseases such as spastic paralysis and full-body cramp disease, and stiff shoulders. Its forms include oral administration methods such as tablets, capsules, granules, powders, and syrups, injections,
Parenteral administration methods include half-opening, etc. These various preparations are formulated according to the conventional method according to the purpose using known adjuvants that are commonly used in the field of pharmaceutical formulation technology, such as crude drugs, excipients, binders, disintegrants, lubricants, and flavoring agents. can be converted into Use of 1-tX Although it varies depending on the symptoms, age, body weight, etc., in the case of oral administration, it can usually be administered 5 q to 50 qt at a time, 1 to 3 times a day.
次に製剤例をあげてさらに具体的に説明する。Next, a more specific explanation will be given using formulation examples.
製剤例１ （錠剤）
トウモロコシ澱粉 ２５．０乳
糖 ８３．３Ｅ
ＰＣ（日本曹達製造）１．２
計１２０■
上記の処方のものを通常の製剤操作により１錠１２０■
の錠剤とした。Formulation example 1 (tablet) Corn starch 25.0 milk
Sugar 83.3E
PC (manufactured by Nippon Soda) 1.2 Total 120■ One tablet of the above formulation is 120■
It was made into tablets.
製剤例２ （カプセル剤）
乳 糖 １５３
．６トウモロコシ澱粉 １００．０ス
テアリン酸マグネシウム １．４計２
８０１９
上記の処方の粉末を混合し、６０メツシユのふるいを通
した後、この粉末２８０７１９を３号ゼラチンカプセル
に入れカプセル剤とした。Formulation example 2 (capsule) Lactose 153
．． 6 Corn starch 100.0 Magnesium stearate 1.4 Total 2
8019 After mixing the powder of the above formulation and passing it through a 60 mesh sieve, the powder 280719 was placed in a No. 3 gelatin capsule to form a capsule.
Claims (1)
等があります▼基（式中、Ｒ＾５は水素原子、低級アル
キル基またはアリール基を示し、Ｒ＾６は水素原子また
は低級アルキル基を示し、Ｙは水酸基、低級アルコキシ
基、アミノ基、モノ若しくはジ低級アルキルアミノ基ま
たは脂環状アミノ基を示す。）を示し、Ｒ＾２は水素原
子、低級アルキル基、ハロゲン原子または式−ＣＯＺ基
（式中、Ｚは水酸基、低級アルコキシ基、アミノ基、モ
ノ若しくはジ低級アルキルアミノ基または脂環状アミノ
基を示す。）を示し、Ｒ＾３は水素原子、カルボキシ基
で置換されていてもよい低級アルキル基、ハロゲン原子
またはニトロ基を示し、Ｒ＾４は水素原子、低級アルキ
ル基、低級アルコキシ基、ハロゲン原子、水酸基、アミ
ノ基、モノ若しくはジ低級アルキルアミノ基、カルボキ
シ基または低級アルコキシカルボニル基を示す。但し、
Ｒ＾１が水素原子を表わす場合には、Ｒ＾２は式−ＣＯ
Ｚ基を表わし、Ｒ＾１が式▲数式、化学式、表等があり
ます▼基を表わす場合には、Ｒ＾２は水素原子、低級ア
ルキル基またはハロゲン原子を表わす。〕で表わされる
インドール誘導体またはその薬理上許容される塩を含有
する中枢性筋弛緩剤。[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R^1 is a hydrogen atom or formula ▲ Numerical formula, chemical formula, table, etc. ▼ Group (In the formula, R^5 is hydrogen represents an atom, a lower alkyl group, or an aryl group, R^6 represents a hydrogen atom or a lower alkyl group, and Y represents a hydroxyl group, a lower alkoxy group, an amino group, a mono- or di-lower alkylamino group, or an alicyclic amino group. ), and R^2 represents a hydrogen atom, a lower alkyl group, a halogen atom, or a -COZ group (wherein Z represents a hydroxyl group, a lower alkoxy group, an amino group, a mono- or di-lower alkylamino group, or an alicyclic amino group). ), R^3 represents a hydrogen atom, a lower alkyl group optionally substituted with a carboxy group, a halogen atom or a nitro group, and R^4 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen Indicates an atom, a hydroxyl group, an amino group, a mono- or di-lower alkylamino group, a carboxy group, or a lower alkoxycarbonyl group. however,
When R^1 represents a hydrogen atom, R^2 has the formula -CO
When it represents a Z group and R^1 represents a group of the formula ▲ which has a numerical formula, chemical formula, table, etc., R^2 represents a hydrogen atom, a lower alkyl group or a halogen atom. ] A central muscle relaxant containing an indole derivative or a pharmacologically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62030774A JPS63198622A (en) | 1987-02-13 | 1987-02-13 | Neutral muscle relaxant containing indole derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62030774A JPS63198622A (en) | 1987-02-13 | 1987-02-13 | Neutral muscle relaxant containing indole derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63198622A true JPS63198622A (en) | 1988-08-17 |
Family
ID=12313030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62030774A Pending JPS63198622A (en) | 1987-02-13 | 1987-02-13 | Neutral muscle relaxant containing indole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63198622A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5229413A (en) * | 1989-05-05 | 1993-07-20 | G. D. Searle & Co. | Compositions containing indole-2-carboxylate compounds for treatment of CNS disorders |
| FR2807659A1 (en) * | 2000-04-13 | 2001-10-19 | Centre Nat Rech Scient | Pharmaceutical composition containing 5-hydroxy-oxindole or related material, useful for treating cancer, anxiety, hyperactivity, insomnia, depression or muscular pain |
-
1987
- 1987-02-13 JP JP62030774A patent/JPS63198622A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5229413A (en) * | 1989-05-05 | 1993-07-20 | G. D. Searle & Co. | Compositions containing indole-2-carboxylate compounds for treatment of CNS disorders |
| FR2807659A1 (en) * | 2000-04-13 | 2001-10-19 | Centre Nat Rech Scient | Pharmaceutical composition containing 5-hydroxy-oxindole or related material, useful for treating cancer, anxiety, hyperactivity, insomnia, depression or muscular pain |
| WO2001078722A1 (en) * | 2000-04-13 | 2001-10-25 | Centre National De La Recherche Scientifique | Pharmaceutical compositions containing 5-hydroxyoxindole and use thereof |
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