JPH0239510B2 - - Google Patents
Info
- Publication number
- JPH0239510B2 JPH0239510B2 JP57097885A JP9788582A JPH0239510B2 JP H0239510 B2 JPH0239510 B2 JP H0239510B2 JP 57097885 A JP57097885 A JP 57097885A JP 9788582 A JP9788582 A JP 9788582A JP H0239510 B2 JPH0239510 B2 JP H0239510B2
- Authority
- JP
- Japan
- Prior art keywords
- sub
- tropyl
- compounds
- alkyl
- migraine
- 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
- 206010027599 migraine Diseases 0.000 claims abstract description 32
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 12
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 abstract description 70
- 125000003545 alkoxy group Chemical group 0.000 abstract description 6
- 125000000217 alkyl group Chemical group 0.000 abstract description 5
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 56
- 239000000203 mixture Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- 239000002253 acid Substances 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- MNJNPLVXBISNSX-PBWFPOADSA-N [(1s,5r)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3,5-dichlorobenzoate Chemical compound C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C1=CC(Cl)=CC(Cl)=C1 MNJNPLVXBISNSX-PBWFPOADSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- 206010019233 Headaches Diseases 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 229960004503 metoclopramide Drugs 0.000 description 8
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 8
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N Benzoyltropein Chemical class CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 231100000869 headache Toxicity 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000002464 receptor antagonist Substances 0.000 description 6
- 229940044551 receptor antagonist Drugs 0.000 description 6
- QTLOKEVDMMEARP-UHFFFAOYSA-N (8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 3,5-dimethoxybenzoate Chemical compound COC1=CC(OC)=CC(C(=O)OC2CC3CCC(N3C)C2)=C1 QTLOKEVDMMEARP-UHFFFAOYSA-N 0.000 description 5
- FKKLHLZFSZGXBN-UHFFFAOYSA-N 1-chloro-3,5-dimethylbenzene Chemical group CC1=CC(C)=CC(Cl)=C1 FKKLHLZFSZGXBN-UHFFFAOYSA-N 0.000 description 5
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 5
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 5
- MZUIOLZHUUHESU-UHFFFAOYSA-N 3-chloro-5-methylbenzoic acid Chemical compound CC1=CC(Cl)=CC(C(O)=O)=C1 MZUIOLZHUUHESU-UHFFFAOYSA-N 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- -1 methoxy, ethoxy, n-propoxy, n-butoxy Chemical group 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000002775 capsule 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
- 229960004704 dihydroergotamine Drugs 0.000 description 3
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- HDDNYFLPWFSBLN-ZSHCYNCHSA-N tropanyl 3,5-dimethylbenzoate Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C1=CC(C)=CC(C)=C1 HDDNYFLPWFSBLN-ZSHCYNCHSA-N 0.000 description 3
- ASWRTDCDFPALAX-PAFGHYSMSA-N (1s,5r)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol;hydrochloride Chemical compound Cl.C1C(O)C[C@H]2CC[C@@H]1N2C ASWRTDCDFPALAX-PAFGHYSMSA-N 0.000 description 2
- QAOJBHRZQQDFHA-UHFFFAOYSA-N 2,3-dichlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1Cl QAOJBHRZQQDFHA-UHFFFAOYSA-N 0.000 description 2
- SJSOFNCYXJUNBT-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1OC SJSOFNCYXJUNBT-UHFFFAOYSA-N 0.000 description 2
- MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 2
- AMRZUHVOHXAKIW-UHFFFAOYSA-N 3-chloro-5-methylbenzoyl chloride Chemical compound CC1=CC(Cl)=CC(C(Cl)=O)=C1 AMRZUHVOHXAKIW-UHFFFAOYSA-N 0.000 description 2
- DUUGKQCEGZLZNO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Chemical compound C1=C(O)C=C2C(CC(=O)O)=CNC2=C1 DUUGKQCEGZLZNO-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- 208000006561 Cluster Headache Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241000219161 Theobroma Species 0.000 description 2
- FBJOIDSZBBTUOV-JXMYBXCISA-N [(1r,5s)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3,5-dimethylbenzoate;hydrochloride Chemical compound Cl.C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C1=CC(C)=CC(C)=C1 FBJOIDSZBBTUOV-JXMYBXCISA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 229960000836 amitriptyline Drugs 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 230000002921 anti-spasmodic effect Effects 0.000 description 2
- 229940125683 antiemetic agent Drugs 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229960003564 cyclizine Drugs 0.000 description 2
- UVKZSORBKUEBAZ-UHFFFAOYSA-N cyclizine Chemical compound C1CN(C)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 UVKZSORBKUEBAZ-UHFFFAOYSA-N 0.000 description 2
- 229960004943 ergotamine Drugs 0.000 description 2
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 2
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- GPSDUZXPYCFOSQ-UHFFFAOYSA-M m-toluate Chemical compound CC1=CC=CC(C([O-])=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-M 0.000 description 2
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluenecarboxylic acid Natural products CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229960003712 propranolol Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000003506 spasmogen Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/12—Oxygen atoms acylated by aromatic or heteroaromatic carboxylic acids, e.g. cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Description
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Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ æ··åç©ãšããŠåã¯ãã以å€ã®æ¹æ³ã§çµã¿åã
ãããã補è¬äžåãå ¥ããããåžéå€åã¯æ äœ
ãšã次ã®äžè¬åŒã®ãããã«ãã³ãŸãšãŒãèªå°äœ
åã¯ãã®è£œè¬äžåãå ¥ããããå¡©ã®ãåäœæäžé
åœã0.5ãªãã100mgã®éãããªãçé çæ²»ççšã®
åäœæäžåœ¢ã®è£œè¬çµæç© ãåŒäžR1ã¯C1âC4ã¢ã«ãã«ãC1âC4ã¢ã«ã³ã
ã·ãåã¯ããã²ã³ãè¡šããã R2ã¯æ°ŽçŽ ãC1âC4ã¢ã«ãã«ãC1âC4ã¢ã«ã³ã
ã·ãåã¯ããã²ã³ãè¡šããããã㊠R3ã¯æ°ŽçŽ ãC1âC4ã¢ã«ãã«ãC1âC4ã¢ã«ã³ã
ã·ãåã¯ããã²ã³ãè¡šãããäœãR2ãæ°ŽçŽ ã®ãš
ãã¯R3ã¯æ°ŽçŽ ã§ãããã ïŒ æ¬¡ã®äžè¬åŒâ²ã®ãããã«ãã³ãŸãšãŒãèªå°
äœ ãåŒäžãR1ã¯C1âC4ã¢ã«ãã«ãC1âC4ã¢ã«ã³
ãã·ãåã¯ããã²ã³ãè¡šããã Râ²2ã¯C1âC4ã¢ã«ãã«åã¯C1âC4ã¢ã«ã³ãã·ã
è¡šããããã㊠Râ²3ã¯ãC1âC4ã¢ã«ãã«åã¯R1ãC1âC4ã¢ã«ã
ã«ã§ãªãå Žåã®ã¿æ°ŽçŽ ãè¡šããåã¯è£œè¬äžåãå ¥
ãããããã®å¡©ã
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8118249 | 1981-06-13 | ||
| GB8118249 | 1981-06-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58978A JPS58978A (ja) | 1983-01-06 |
| JPH0239510B2 true JPH0239510B2 (ja) | 1990-09-05 |
Family
ID=10522493
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57097885A Granted JPS58978A (ja) | 1981-06-13 | 1982-06-09 | ãããã«ãã³ãŸãšãŒãèªå°äœåã³çé çã®æ²»çè¬ |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US4563465A (ja) |
| EP (1) | EP0067770B1 (ja) |
| JP (1) | JPS58978A (ja) |
| AT (1) | ATE71525T1 (ja) |
| AU (1) | AU549640B2 (ja) |
| CA (1) | CA1220141A (ja) |
| DE (1) | DE3280390D1 (ja) |
| ES (1) | ES8401067A1 (ja) |
| ZA (1) | ZA823884B (ja) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2531083B1 (fr) * | 1982-06-29 | 1986-11-28 | Sandoz Sa | Nouveaux derives de la piperidine, leur preparation et leur utilisation comme medicaments |
| JPS5936675A (ja) * | 1982-07-13 | 1984-02-28 | ãµã³ãã»ã¢ã¯ããšã³ã²ãŒã«ã·ã€ãã | äºç°æ§è€çŽ ç°åŒã«ã«ãã³é žã¢ã¶ãã·ã¯ãã¢ã«ãã«ãšã¹ãã«ãŸãã¯ã¢ãã |
| CH664567A5 (de) * | 1983-08-26 | 1988-03-15 | Sandoz Ag | Aromatische carbonsaeure- und sulfonsaeureester oder -amide. |
| DE3445377A1 (de) * | 1983-12-23 | 1985-07-04 | Sandoz-Patent-GmbH, 7850 Lörrach | Carbocylische und heterocyclische carbonsaeureester und -amide von ueberbrueckten und nicht ueberbrueckten cyclischen stickstoffhaltigen aminen oder alkoholen |
| CH667657A5 (de) * | 1985-01-07 | 1988-10-31 | Sandoz Ag | Carbocyclische und heterocyclische carbonylmethylen- und methylpiperidine und -pyrrolidine. |
| GB8518658D0 (en) * | 1985-07-24 | 1985-08-29 | Glaxo Group Ltd | Medicaments |
| US4906755A (en) * | 1986-11-03 | 1990-03-06 | Merrell Dow Pharmaceuticals Inc. | Esters of hexahydro-8-hydroxy-2,6-methano-2H-quinolizin-3-(4H)-one and related compounds |
| GB8701022D0 (en) * | 1987-01-19 | 1987-02-18 | Beecham Group Plc | Treatment |
| US5017573A (en) * | 1988-07-29 | 1991-05-21 | Dainippon Pharmaceutical Co., Ltd. | Indazole-3-carboxylic acid derivatives |
| US5166341A (en) * | 1988-07-29 | 1992-11-24 | Dainippon Pharmaceutical Co., Ltd. | 6-amino-1,4-hexahydro-1H-diazepine derivatives |
| US5126343A (en) * | 1989-09-11 | 1992-06-30 | G. D. Searle & Co. | N-azabicyclo [3.3.0]octane amides of aromatic acids |
| CA2030051C (en) * | 1989-11-17 | 2001-08-07 | Haruhiko Kikuchi | Indole derivatives |
| JP3026845B2 (ja) * | 1991-02-20 | 2000-03-27 | æ¥æž 補ç²æ ªåŒäŒç€Ÿ | ãããªãžã³èªå°äœ |
| US5460972A (en) * | 1991-04-08 | 1995-10-24 | Research Foundation Of The State University Of New York | Ionized magnesium2+ concentrations in biological samples |
| JP2541231Y2 (ja) * | 1992-10-06 | 1997-07-16 | 圊倫 ææ | èç«çšå®å šæ£ |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3170927A (en) * | 1965-02-23 | O chzoh |
-
1982
- 1982-06-01 CA CA000404222A patent/CA1220141A/en not_active Expired
- 1982-06-02 ZA ZA823884A patent/ZA823884B/xx unknown
- 1982-06-08 ES ES512925A patent/ES8401067A1/es not_active Expired
- 1982-06-09 JP JP57097885A patent/JPS58978A/ja active Granted
- 1982-06-10 AU AU84749/82A patent/AU549640B2/en not_active Ceased
- 1982-06-11 AT AT82401060T patent/ATE71525T1/de not_active IP Right Cessation
- 1982-06-11 DE DE8282401060T patent/DE3280390D1/de not_active Expired - Fee Related
- 1982-06-11 EP EP82401060A patent/EP0067770B1/en not_active Expired - Lifetime
-
1984
- 1984-12-13 US US06/681,984 patent/US4563465A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| AU549640B2 (en) | 1986-02-06 |
| EP0067770B1 (en) | 1992-01-15 |
| CA1220141A (en) | 1987-04-07 |
| US4563465A (en) | 1986-01-07 |
| JPS58978A (ja) | 1983-01-06 |
| DE3280390D1 (de) | 1992-02-27 |
| ATE71525T1 (de) | 1992-02-15 |
| EP0067770A2 (en) | 1982-12-22 |
| ES512925A0 (es) | 1983-12-01 |
| AU8474982A (en) | 1982-12-23 |
| ES8401067A1 (es) | 1983-12-01 |
| EP0067770A3 (en) | 1983-04-06 |
| ZA823884B (en) | 1983-03-30 |
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