FI84349C - Foerfarande foer framstaellning av en farmakologiskt vaerdefull foerening. - Google Patents
Foerfarande foer framstaellning av en farmakologiskt vaerdefull foerening. Download PDFInfo
- Publication number
- FI84349C FI84349C FI850323A FI850323A FI84349C FI 84349 C FI84349 C FI 84349C FI 850323 A FI850323 A FI 850323A FI 850323 A FI850323 A FI 850323A FI 84349 C FI84349 C FI 84349C
- Authority
- FI
- Finland
- Prior art keywords
- methyl
- formula
- tetrahydro
- compound
- carbazol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 25
- 230000000144 pharmacologic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 126
- 239000000203 mixture Substances 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 10
- 230000001590 oxidative effect Effects 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 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 claims 1
- ARFOLUOIUFOCJX-UHFFFAOYSA-N 9-cyclopentyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C3CCCC3)=C2CC1 ARFOLUOIUFOCJX-UHFFFAOYSA-N 0.000 claims 1
- VRSLTNZJOUZKLX-UHFFFAOYSA-N Ondansetron hydrochloride Chemical compound O.O.Cl.CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 VRSLTNZJOUZKLX-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 103
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 76
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000007787 solid Substances 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 235000019441 ethanol Nutrition 0.000 description 35
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 239000000725 suspension Substances 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- -1 prop-2-enyl Chemical group 0.000 description 17
- 239000002904 solvent Substances 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
- 239000011976 maleic acid Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000001537 neural effect Effects 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 7
- 239000007800 oxidant agent Substances 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000004423 acyloxy group Chemical group 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 208000019695 Migraine disease Diseases 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 238000007429 general method Methods 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 150000002688 maleic acid derivatives Chemical class 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 150000004677 hydrates Chemical class 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 206010027599 migraine Diseases 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZBFZXENHYIJZGA-UHFFFAOYSA-N 2,3,4,4a-tetrahydrocarbazol-1-one Chemical group C1=CC=C2C3CCCC(=O)C3=NC2=C1 ZBFZXENHYIJZGA-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 230000000202 analgesic effect Effects 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
- 150000002148 esters Chemical class 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 230000008676 import Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- FOTRUJUPLHRVNU-QNBGGDODSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid;hydrate Chemical compound O.C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 FOTRUJUPLHRVNU-QNBGGDODSA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 2
- ZHIDLFGPDBGBLX-UHFFFAOYSA-N 3-(1h-imidazol-2-ylmethyl)-2,3,4,4a-tetrahydrocarbazol-1-one Chemical class C1C(C2=CC=CC=C2N=2)C=2C(=O)CC1CC1=NC=CN1 ZHIDLFGPDBGBLX-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 2
- 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 2
- 206010026749 Mania Diseases 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- AMLYRCOEFHJSFS-UHFFFAOYSA-N carbazol-1-one Chemical group C1=CC=C2C3=CC=CC(=O)C3=NC2=C1 AMLYRCOEFHJSFS-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical compound [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- XCGSFFUVFURLIX-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(C=3C=CC=C4NC=C(C=34)C2)=C1)C)C1=CC=CC=C1 XCGSFFUVFURLIX-VFGNJEKYSA-N 0.000 description 2
- 229960004943 ergotamine Drugs 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
- 150000002170 ethers Chemical class 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
- 230000008570 general process Effects 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- CQQJSOXDEFZGFG-UHFFFAOYSA-N imidazo[4,5-d]imidazole Chemical group C1=NC2=NC=NC2=N1 CQQJSOXDEFZGFG-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 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
- 230000015654 memory Effects 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 230000010004 neural pathway Effects 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000004053 quinones Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 2
- DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- NTOIKDYVJIWVSU-WOJBJXKFSA-N (2r,3r)-2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical class C1=CC(C)=CC=C1C(=O)[C@@](O)(C(O)=O)[C@](O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-WOJBJXKFSA-N 0.000 description 1
- DAXJNUBSBFUTRP-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6-(hydroxymethyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(CO)C2=C1 DAXJNUBSBFUTRP-RTQNCGMRSA-N 0.000 description 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- FSJSRSHEOFVRHM-UHFFFAOYSA-N 1-methyl-3-[(2-methylimidazol-1-yl)methyl]carbazol-4-one Chemical compound CC1=NC=CN1CC(C1=O)=CC(C)=C2C1=C1C=CC=CC1=N2 FSJSRSHEOFVRHM-UHFFFAOYSA-N 0.000 description 1
- VNHXNDULTGGTII-UHFFFAOYSA-N 1-methylcarbazol-4-one Chemical compound N1=C2C=CC=CC2=C2C1=C(C)C=CC2=O VNHXNDULTGGTII-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- MKBBSFGKFMQPPC-UHFFFAOYSA-N 2-propyl-1h-imidazole Chemical compound CCCC1=NC=CN1 MKBBSFGKFMQPPC-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- KLUNAVKHVFZQKF-UHFFFAOYSA-N 3-(imidazol-1-ylmethyl)-1,2,3,9-tetrahydrocarbazol-4-one Chemical compound C1CC=2NC3=CC=CC=C3C=2C(=O)C1CN1C=CN=C1 KLUNAVKHVFZQKF-UHFFFAOYSA-N 0.000 description 1
- NPVYFSMKVAWIGI-UHFFFAOYSA-N 3-[(2-methylimidazol-1-yl)methyl]-9-prop-2-enyl-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2CC=C)=C2CC1 NPVYFSMKVAWIGI-UHFFFAOYSA-N 0.000 description 1
- PDTRUKJPGPCEGC-UHFFFAOYSA-N 3-[(2-methylimidazol-1-yl)methyl]carbazol-4-one Chemical compound CC=1N(C=CN1)CC1=CC=C2N=C3C=CC=CC3=C2C1=O PDTRUKJPGPCEGC-UHFFFAOYSA-N 0.000 description 1
- UEWOZJZAMBVKAE-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-1,2,3,9-tetrahydrocarbazol-4-one Chemical compound N1C2=CC=CC=C2C2=C1CCC(CN(C)C)C2=O UEWOZJZAMBVKAE-UHFFFAOYSA-N 0.000 description 1
- YNCCNQIEKQPTQU-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-9-phenyl-2,3-dihydro-1h-carbazol-4-one;hydrochloride Chemical compound Cl.O=C1C(CN(C)C)CCC2=C1C1=CC=CC=C1N2C1=CC=CC=C1 YNCCNQIEKQPTQU-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- CGMCWBNRQVJWOH-UHFFFAOYSA-N CC1=NC=CN1CC2CCC3=NC4=CC=CC=C4C3C2=O Chemical compound CC1=NC=CN1CC2CCC3=NC4=CC=CC=C4C3C2=O CGMCWBNRQVJWOH-UHFFFAOYSA-N 0.000 description 1
- KLVFKAZHMDQHJJ-UHFFFAOYSA-N CN(C)CC1CCC2=C(C1)C3=CC=CC=C3N2 Chemical compound CN(C)CC1CCC2=C(C1)C3=CC=CC=C3N2 KLVFKAZHMDQHJJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 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
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 208000020114 Schizophrenia and other psychotic disease Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- KZCSGONCLLTHRA-UHFFFAOYSA-N carbazol-4-one Chemical compound C1=CC=CC2=C3C(=O)C=CC=C3N=C21 KZCSGONCLLTHRA-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
- ITZXULOAYIAYNU-UHFFFAOYSA-N cerium(4+) Chemical compound [Ce+4] ITZXULOAYIAYNU-UHFFFAOYSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- NSNHWTBQMQIDCF-UHFFFAOYSA-N dihydrate;hydrochloride Chemical compound O.O.Cl NSNHWTBQMQIDCF-UHFFFAOYSA-N 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 229960002523 mercuric chloride Drugs 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- FGHSTPNOXKDLKU-UHFFFAOYSA-N nitric acid;hydrate Chemical compound O.O[N+]([O-])=O FGHSTPNOXKDLKU-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 230000037047 psychomotor activity Effects 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000004622 sleep time Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848401888A GB8401888D0 (en) | 1984-01-25 | 1984-01-25 | Heterocyclic compounds |
| GB8401888 | 1984-01-25 | ||
| GB8425959 | 1984-10-15 | ||
| GB848425959A GB8425959D0 (en) | 1984-10-15 | 1984-10-15 | Heterocyclic compounds |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI850323A0 FI850323A0 (fi) | 1985-01-25 |
| FI850323L FI850323L (fi) | 1985-07-26 |
| FI84349B FI84349B (fi) | 1991-08-15 |
| FI84349C true FI84349C (fi) | 1991-11-25 |
Family
ID=26287221
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI850323A FI84349C (fi) | 1984-01-25 | 1985-01-25 | Foerfarande foer framstaellning av en farmakologiskt vaerdefull foerening. |
Country Status (29)
Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4695578A (en) * | 1984-01-25 | 1987-09-22 | Glaxo Group Limited | 1,2,3,9-tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, composition containing them, and method of using them to treat neuronal 5HT function disturbances |
| DE3680123D1 (en) * | 1985-01-23 | 1991-08-14 | Glaxo Group Ltd | Tetrahydrocarbazolonderivate. |
| DE3689974T2 (de) * | 1985-03-14 | 1994-11-03 | Beecham Group Plc | Arzneimittel zur Behandlung von Emesis. |
| US5578628A (en) * | 1985-06-25 | 1996-11-26 | Glaxo Group Limited | Medicaments for the treatment of nausea and vomiting |
| GB8516083D0 (en) * | 1985-06-25 | 1985-07-31 | Glaxo Group Ltd | Heterocyclic compounds |
| GB8518743D0 (en) * | 1985-07-24 | 1985-08-29 | Glaxo Group Ltd | Heterocyclic compounds |
| GB8518741D0 (en) * | 1985-07-24 | 1985-08-29 | Glaxo Group Ltd | Process |
| GB8518745D0 (en) | 1985-07-24 | 1985-08-29 | Glaxo Group Ltd | Heterocyclic compounds |
| GB8518742D0 (en) * | 1985-07-24 | 1985-08-29 | Glaxo Group Ltd | Process |
| GB8518658D0 (en) * | 1985-07-24 | 1985-08-29 | Glaxo Group Ltd | Medicaments |
| US5204356A (en) * | 1985-07-24 | 1993-04-20 | Glaxo Group Limited | Treatment of anxiety |
| GB8617994D0 (en) * | 1986-07-23 | 1986-08-28 | Glaxo Group Ltd | Heterocyclic compounds |
| HU895334D0 (en) * | 1986-07-30 | 1990-01-28 | Sandoz Ag | Process for the preparation of nasal pharmaceutical compositions |
| AT396870B (de) * | 1986-08-07 | 1993-12-27 | Sandoz Ag | Verfahren zur herstellung einer galenischen formulierung zur nasalen verabreichung von serotoninantagonisten |
| GB8623819D0 (en) * | 1986-10-03 | 1986-11-05 | Glaxo Group Ltd | Heterocyclic compounds |
| GB8627909D0 (en) * | 1986-11-21 | 1986-12-31 | Glaxo Group Ltd | Medicaments |
| WO1988003801A1 (en) * | 1986-11-21 | 1988-06-02 | Glaxo Group Limited | Medicaments for treatment or prevention of withdrawal syndrome |
| GR871809B (en) * | 1986-11-28 | 1988-03-07 | Glaxo Group Ltd | Process for the preparation of tricyclic ketones |
| GB8628475D0 (en) * | 1986-11-28 | 1987-01-07 | Glaxo Group Ltd | Medicaments |
| GB8812002D0 (en) * | 1988-05-20 | 1988-06-22 | Glaxo Group Ltd | Chemical compounds |
| US5202343A (en) * | 1986-11-28 | 1993-04-13 | Glaxo Group Limited | Tricyclic ketones useful as HT3 -receptor antagonists |
| JPS63277622A (ja) * | 1986-12-17 | 1988-11-15 | グラクソ、グループ、リミテッド | 医薬 |
| US4845115A (en) * | 1986-12-17 | 1989-07-04 | Glaxo Group Limited | Method of medical treatment |
| GB8630071D0 (en) * | 1986-12-17 | 1987-01-28 | Glaxo Group Ltd | Medicaments |
| US5190954A (en) * | 1986-12-17 | 1993-03-02 | Glaxo Group Limited | Methods for the treatment of cognitive disorders |
| GB8630079D0 (en) * | 1986-12-17 | 1987-01-28 | Glaxo Group Ltd | Medicaments |
| US5200414A (en) * | 1986-12-17 | 1993-04-06 | Glaxo Group Limited | Methods for the treatment of cognitive disorders |
| DE3876006T2 (de) * | 1987-04-14 | 1993-03-25 | Glaxo Group Ltd | Keton-derivate. |
| DE3874229T2 (de) * | 1987-06-16 | 1993-03-25 | British Tech Group | Verwendung von dioxopiperidin-derivaten zur herstellung eines topischen praeparates als analgetika. |
| DE3822792C2 (de) * | 1987-07-11 | 1997-11-27 | Sandoz Ag | Neue Verwendung von 5HT¶3¶-Antagonisten |
| GB8723157D0 (en) * | 1987-10-02 | 1987-11-04 | Beecham Group Plc | Compounds |
| CA1304082C (en) * | 1987-10-22 | 1992-06-23 | Tetsuya Tahara | Benzoxazine compounds and pharmaceutical use thereof |
| EP0317088A1 (en) * | 1987-10-22 | 1989-05-24 | Glaxo Group Limited | Ketone derivatives |
| US5225431A (en) * | 1987-10-23 | 1993-07-06 | Burroughs Wellcome Co. | Therapeutic substituted indole compounds and compositions thereof |
| GB8805269D0 (en) * | 1988-03-04 | 1988-04-07 | Glaxo Group Ltd | Medicaments |
| JPH0249772A (ja) * | 1988-04-07 | 1990-02-20 | Glaxo Group Ltd | イミダゾール誘導体 |
| DK185489A (da) * | 1988-04-22 | 1989-10-23 | Duphar Int Res | Imidazolylmethyl-cycloalkanoebaaindoloner, deres fremstilling og anvendelse |
| JPH0256485A (ja) * | 1988-04-27 | 1990-02-26 | Glaxo Group Ltd | ラクタム誘導体 |
| GB8812636D0 (en) * | 1988-05-27 | 1988-06-29 | Glaxo Group Ltd | Chemical compounds |
| US5173493A (en) * | 1988-09-27 | 1992-12-22 | Fujisawa Pharmaceutical Company, Ltd. | Pyridoindole derivatives and processes for preparation thereof |
| AU627221B2 (en) * | 1988-09-27 | 1992-08-20 | Fujisawa Pharmaceutical Co., Ltd. | Pyridoindole derivatives and processes for preparation thereof |
| US5290785A (en) * | 1988-09-27 | 1994-03-01 | Fujisawa Pharmaceutical Co., Ltd. | Therapeutic agent for ischemic diseases |
| FR2639944B1 (fr) * | 1988-12-06 | 1991-01-18 | Adir | Nouveaux derives de l'indole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US5223625A (en) * | 1988-12-22 | 1993-06-29 | Duphar International Research B.V. | Annelated indolo [3,2,-C]lactams |
| EP0377238A1 (en) * | 1988-12-22 | 1990-07-11 | Duphar International Research B.V | New annelated indolo (3,2-c)-lactams |
| CA2004911A1 (en) * | 1988-12-22 | 1990-06-22 | Mitsuaki Ohta | 4,5,6,7-tetrahydrobenzimidazole derivatives |
| EP0392663A1 (en) * | 1989-03-13 | 1990-10-17 | Ono Pharmaceutical Co., Ltd. | Carboline derivative as a 5-HT3 receptor antagonist |
| JPH0669963B2 (ja) * | 1989-04-21 | 1994-09-07 | サンド・アクチエンゲゼルシャフト | ５ｈｔ▲下３▼受容体拮抗薬の治療的用途 |
| GB8914804D0 (en) * | 1989-06-28 | 1989-08-16 | Glaxo Group Ltd | Process |
| US5276050A (en) * | 1989-08-01 | 1994-01-04 | Glaxo Group Limited | Medicaments |
| GB8917557D0 (en) * | 1989-08-01 | 1989-09-13 | Glaxo Group Ltd | Medicaments |
| US5126343A (en) * | 1989-09-11 | 1992-06-30 | G. D. Searle & Co. | N-azabicyclo [3.3.0]octane amides of aromatic acids |
| GB2236751B (en) | 1989-10-14 | 1993-04-28 | Wyeth John & Brother Ltd | Heterocyclic compounds |
| GB8928837D0 (en) * | 1989-12-21 | 1990-02-28 | Beecham Group Plc | Pharmaceuticals |
| US5187166A (en) * | 1990-07-31 | 1993-02-16 | Nisshin Flour Milling Co., Ltd. | Azabicyclo derivatives and their use as antiemetics |
| WO1993000074A1 (en) | 1991-06-26 | 1993-01-07 | Sepracor, Inc. | Method and compositions for treating emesis, nausea and other disorders using optically pure r(+) ondansetron |
| JPH05310732A (ja) * | 1992-03-12 | 1993-11-22 | Mitsubishi Kasei Corp | シンノリン−３−カルボン酸誘導体 |
| ES2043535B1 (es) * | 1992-03-13 | 1994-08-01 | Vita Invest Sa | Procedimiento para la obtencion de la 1,2,3,9-tetrahidro-9-metil-3-(2-metil-1h-imidazol-1-il)metil*-4h-carbazol-4-ona. |
| HU212934B (en) | 1992-10-14 | 1996-12-30 | Richter Gedeon Vegyeszet | Process for producing novel alkoxalylated carbazolone derivatives |
| CA2106642C (en) * | 1992-10-14 | 2005-08-16 | Peter Bod | Carbazolone derivatives and process for preparing the same |
| CA2157671A1 (en) * | 1993-03-08 | 1994-09-15 | Kiyotaka Katsuta | Medicament for treating or preventing cerebrovascular diseases |
| GB9310756D0 (en) * | 1993-05-25 | 1993-07-14 | Glaxo Lab Sa | Compositions |
| GB2325408B (en) * | 1994-06-28 | 1999-01-27 | Kenneth Francis Prendergast | Chewing gum formulation comprising ondansetron |
| GB9423588D0 (en) * | 1994-11-22 | 1995-01-11 | Glaxo Wellcome Inc | Compositions |
| US6365743B1 (en) | 1995-10-13 | 2002-04-02 | Duphar International Research B.V. | Process for the preparation of enantiomerically pure imidazolyl compounds |
| AU702594B2 (en) * | 1995-10-13 | 1999-02-25 | Duphar International Research B.V. | Process for the preparation of enantiomerically pure imidazolyl compounds |
| US5969137A (en) * | 1996-09-19 | 1999-10-19 | Virginia Commonwealth University | Benzylamidine derivatives with serotonin receptor binding activity |
| EP1181015A2 (en) | 1999-03-01 | 2002-02-27 | Sepracor Inc. | Methods for treating apnea and apnea disorders using optically pure r(+)ondansetron |
| EP1207160A1 (en) * | 2000-11-20 | 2002-05-22 | Hanmi Pharm. Co., Ltd. | Process for the preparation of 1,2,3,9-tetrahydro-9-methyl-3-((2-methyl-1H-imidazol-1-yl)-methyl)-4H-carbazol-4-one |
| RU2207340C2 (ru) * | 2001-08-10 | 2003-06-27 | Ципла Лтд. | Способ получения 1,2,3,9-тетрагидро-9-метил-3-[(2-метил-1н-имидазол-1-ил)метил]-4н-карбазол -4-она или его фармацевтически приемлемых солей |
| PT1499623E (pt) | 2002-04-29 | 2007-08-10 | Teva Gyogyszergyar Zartkoeruee | ''processo papa a preparação de 1, 2, 3, 9-tetra-hidro-9-metil-3- [(2-metil-1h-imidazol-1-il) metil] -4h-carbazol-4-ona'' |
| FI6164U1 (fi) * | 2003-01-09 | 2004-03-15 | Synthon Bv | Ondansetronmuotoja |
| GB2398071B (en) * | 2003-01-24 | 2006-06-07 | Synthon Bv | Process for making ondansetron and intermediate thereof |
| ES2238001B1 (es) * | 2004-01-21 | 2006-11-01 | Vita Cientifica, S.L. | Nuevas formas polimorficas de ondansetron, procedimientos para su preparacion, composiciones farmaceuticas que los contienen y su uso como aantiemeticos. |
| WO2005108392A2 (en) | 2004-05-07 | 2005-11-17 | Taro Pharmaceutical Industries Ltd. | Process for preparing ondansetron hydrochloride dihydrate having a defined particle size |
| WO2007004041A2 (en) * | 2005-07-05 | 2007-01-11 | Orchid Research Laboratories Limited | New compounds and their pharmaceutical use |
| US8580730B2 (en) | 2009-05-20 | 2013-11-12 | (Inserm) Institut National De La Sante Et De La Recherche Medicale | Methods of treating lesional vestibular disorders by administering serotonin 5-HT3 receptor antagonists |
| ES2432618T3 (es) | 2009-05-20 | 2013-12-04 | Inserm (Institut National De La Santé Et De La Recherche Medicale) | Antagonistas del receptor 5-HT3 de serotonina para usar en el tratamiento o prevención de una patología del oído interno con déficit vestibular |
| CN115611864A (zh) * | 2022-11-01 | 2023-01-17 | 常州兰陵制药有限公司 | 一种昂丹司琼类化合物及其制备方法与应用 |
| GB202301322D0 (en) | 2023-01-30 | 2023-03-15 | Therakind Ltd | Antiemetic pharmaceutical compositions for nasal delivery |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3634420A (en) * | 1969-05-09 | 1972-01-11 | American Cyanamid Co | 3(morpholinomethyl)-2 3-dihydro-carbazol-4(1h)-ones |
| US3740404A (en) * | 1969-05-09 | 1973-06-19 | American Cyanamid Co | Piperidinomethylenedihydrocarbazolones |
| DE3680123D1 (en) * | 1985-01-23 | 1991-08-14 | Glaxo Group Ltd | Tetrahydrocarbazolonderivate. |
-
1985
- 1985-01-25 HU HU85296A patent/HU193592B/hu unknown
- 1985-01-25 FI FI850323A patent/FI84349C/fi not_active IP Right Cessation
- 1985-01-25 DE DE19853502508 patent/DE3502508A1/de active Granted
- 1985-01-25 IT IT47600/85A patent/IT1182150B/it active Protection Beyond IP Right Term
- 1985-01-25 NZ NZ210940A patent/NZ210940A/xx unknown
- 1985-01-25 LU LU88268C patent/LU88268I2/xx unknown
- 1985-01-25 LU LU85743A patent/LU85743A1/fr active Protection Beyond IP Right Term
- 1985-01-25 AU AU38097/85A patent/AU579132B2/en not_active Expired
- 1985-01-25 KR KR1019850000454A patent/KR920003064B1/ko not_active Expired
- 1985-01-25 ES ES539852A patent/ES8609309A1/es not_active Expired
- 1985-01-25 SE SE8500368A patent/SE460359B/sv not_active IP Right Cessation
- 1985-01-25 DK DK035785A patent/DK169521B1/da not_active IP Right Cessation
- 1985-01-25 IE IE187/85A patent/IE57809B1/en not_active IP Right Cessation
- 1985-01-25 BE BE0/214394A patent/BE901576A/fr not_active IP Right Cessation
- 1985-01-25 IL IL74165A patent/IL74165A/xx not_active IP Right Cessation
- 1985-01-25 GR GR850219A patent/GR850219B/el active IP Right Revival
- 1985-01-25 GB GB08501889A patent/GB2153821B/en not_active Expired
- 1985-01-25 CH CH346/85A patent/CH664152A5/fr not_active IP Right Cessation
- 1985-01-25 NO NO850300A patent/NO164025C/no not_active IP Right Cessation
- 1985-01-25 DE DE1993175046 patent/DE19375046I2/de active Active
- 1985-01-25 PT PT79890A patent/PT79890B/pt unknown
- 1985-01-25 PH PH31770A patent/PH22672A/en unknown
- 1985-01-25 FR FR8501056A patent/FR2561244B1/fr not_active Expired
- 1985-01-25 CA CA000472888A patent/CA1252793A/en not_active Expired
- 1985-01-25 AT AT204/85A patent/AT392276B/de not_active IP Right Cessation
- 1985-01-25 NL NLAANVRAGE8500202,A patent/NL190373C/xx not_active IP Right Cessation
- 1985-10-31 ES ES548430A patent/ES8708224A1/es not_active Expired
-
1986
- 1986-06-16 ES ES556101A patent/ES8801247A1/es not_active Expired
-
1989
- 1989-02-09 SG SG70/89A patent/SG7089G/en unknown
- 1989-04-20 HK HK331/89A patent/HK33189A/xx not_active IP Right Cessation
- 1989-07-21 CY CY1479A patent/CY1479A/en unknown
-
1991
- 1991-12-23 SK SK4043-91A patent/SK277923B6/sk unknown
- 1991-12-23 CZ CS914043A patent/CZ404391A3/cs unknown
-
1994
- 1994-05-31 NL NL940009C patent/NL940009I2/nl unknown
- 1994-11-09 NO NO1994022C patent/NO1994022I1/no unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI84349C (fi) | Foerfarande foer framstaellning av en farmakologiskt vaerdefull foerening. | |
| US4695578A (en) | 1,2,3,9-tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, composition containing them, and method of using them to treat neuronal 5HT function disturbances | |
| EP0219193B1 (en) | Tetrahydrocarbazolone derivatives, processes for their preparation and pharmaceutical compositions containing them | |
| EP0191562B1 (en) | Tetrahydrocarbazolone derivatives | |
| EP0210840B1 (en) | Substituted imidazolylmethyltetrahydro-carbazolones | |
| WO1998056768A1 (fr) | Derives tricycliques de pyrrole ou de pyrazole | |
| US5563147A (en) | Serotonerbic tetrahydropyridoindoles | |
| US5849746A (en) | Substituted 1,4-piperazine-heteroaryl derivatives as 5-HT1D receptor agonists | |
| CZ2000320A3 (cs) | Deriváty 4-oxo-3,5dihydro-4H-pyridazino[4,5-b]indol-1-acetamidu a farmaceutický prostředek, který je obsahuje | |
| HU188475B (en) | Process for producing benzothiopyrano-pyridinones | |
| RU2098418C1 (ru) | Конденсированное производное тиазола или его фармацевтически приемлемая соль, фармацевтическая композиция, проявляющая активность агониста 5-нт*003-рецептора на его основе | |
| JPH01258673A (ja) | ケトン誘導体 | |
| US6127388A (en) | Azetidine, pyrrolidine and piperidine derivatives as 5-HT1D receptor agonists | |
| IE60265B1 (en) | Condensed diazepinones | |
| EP0072029B1 (de) | Triazolobenzazepine, Verfahren und Zwischenprodukte zu deren Herstellung und diese enthaltende Arzneimittel | |
| US4482714A (en) | Pyrazino[2',3'-3,4]pyrido[1,2-a]indole derivatives | |
| US5994374A (en) | Substituted 1-indolylpropyl-4-benzyl-tetrahydropyridine derivatives | |
| US4515949A (en) | [2-(1H-indol-1-yl)ethyl]-2-piperazine and pyrido[1,2-a]indol-9-one as intermediates for pyrazino(2,3-3,4)pyrido(1,2-a) indoles which are useful for treating hypertension in mammals | |
| RU2081117C1 (ru) | Производные лактама или их физиологические приемлемые соли или сольваты | |
| PT93668A (pt) | Processo para a preparacao de derivados de benzazepina e de benzotiazepina com accao vasodilatadora | |
| EP0726257B1 (en) | 1-(Hetero)Arylvinyl-5H-2,3-benzodiazepine derivatives useful for the treatment of central nervous system disorders, and benzopyrylium intermediates for their preparation | |
| JPH0378862B2 (enrdf_load_stackoverflow) | ||
| FI89484B (fi) | Foerfarande foer framstaellning av terapeutiskt aktiva tetrahydro-2-/(imidazol-4-yl)metyl/pyrido(4,3-b)indol- och azepino-/4,3-b/indol-1-oner | |
| PL81337B1 (en) | Indolazonine and indolazecine derivs. - having pharmacological activity[FR2059489A1] | |
| DE4120109A1 (de) | 3-aryl- oder 3-hetaryl-(beta)-carboline, deren herstellung und verwendung in arzneimitteln |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ND | Supplementary protection certificate (spc) granted | ||
| SPCG | Supplementary protection certificate granted |
Spc suppl protection certif: L59 Extension date: 20050223 |
|
| FG | Patent granted |
Owner name: GLAXO GROUP LIMITED |
|
| MA | Patent expired |