NO311724B1 - Heksahydro-pyrido (4,3-B)indolderivater som antipsykotiske legemidler - Google Patents

Heksahydro-pyrido (4,3-B)indolderivater som antipsykotiske legemidler Download PDF

Info

Publication number: NO311724B1
Authority: NO; Norway
Prior art keywords: formula; hydrogen; alkyl; pyrido; alk
Prior art date: 1996-05-23

Application number

NO19985389A

Other languages

English (en)

Norwegian (no)

Other versions

NO985389L (no

NO985389D0 (no

Inventor

Ludo Edmond Josephine Kennis

Josephus Carolus Mertens

Original Assignee

Janssen Pharmaceutica Nv

Priority date (The priority date 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 date listed.)

1996-05-23

Filing date

1998-11-19

Publication date

2002-01-14

1998-11-19 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1998-11-19 Publication of NO985389D0 publication Critical patent/NO985389D0/no

1999-01-20 Publication of NO985389L publication Critical patent/NO985389L/no

2002-01-14 Publication of NO311724B1 publication Critical patent/NO311724B1/no

Links

BPPMRCNUQCVVFJ-UHFFFAOYSA-N 2,3,4,4a,5,9b-hexahydro-1h-pyrido[4,3-b]indole Chemical class N1C2=CC=CC=C2C2C1CCNC2 BPPMRCNUQCVVFJ-UHFFFAOYSA-N 0.000 title claims description 7
239000000164 antipsychotic agent Substances 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 86
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 28
239000001257 hydrogen Substances 0.000 claims abstract description 24
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
238000002360 preparation method Methods 0.000 claims abstract description 14
239000003814 drug Substances 0.000 claims abstract description 6
125000003118 aryl group Chemical group 0.000 claims abstract description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 9
125000001475 halogen functional group Chemical group 0.000 claims abstract 3
239000002253 acid Substances 0.000 claims description 21
238000000034 method Methods 0.000 claims description 15
239000002585 base Substances 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 13
238000006243 chemical reaction Methods 0.000 claims description 13
150000003254 radicals Chemical class 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
239000004480 active ingredient Substances 0.000 claims description 6
125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 6
239000012442 inert solvent Substances 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 5
150000001204 N-oxides Chemical group 0.000 claims description 4
239000012458 free base Substances 0.000 claims description 3
150000002576 ketones Chemical class 0.000 claims description 3
HFBVQUOBAIWWLM-UHFFFAOYSA-N 3-[2-(8-fluoro-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indol-2-yl)ethyl]-2-methylpyrido[1,2-a]pyrimidin-4-one Chemical compound N1C2=CC=C(F)C=C2C(C2)C1CCN2CCC(C1=O)=C(C)N=C2N1C=CC=C2 HFBVQUOBAIWWLM-UHFFFAOYSA-N 0.000 claims description 2
150000001299 aldehydes Chemical class 0.000 claims description 2
239000003513 alkali Substances 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims description 2
230000009466 transformation Effects 0.000 claims description 2
239000000203 mixture Substances 0.000 abstract description 47
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 24
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 24
-1 mercapto, amino Chemical group 0.000 abstract description 17
229960003638 dopamine Drugs 0.000 abstract description 12
229940076279 serotonin Drugs 0.000 abstract description 12
230000000694 effects Effects 0.000 abstract description 6
125000004356 hydroxy functional group Chemical group O* 0.000 abstract description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 2
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 1
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
125000004093 cyano group Chemical group *C#N 0.000 abstract 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
239000000543 intermediate Substances 0.000 description 46
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
239000000243 solution Substances 0.000 description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 20
239000002904 solvent Substances 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
230000003042 antagnostic effect Effects 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 9
229960004046 apomorphine Drugs 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
229960002748 norepinephrine Drugs 0.000 description 9
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
241000700159 Rattus Species 0.000 description 8
239000003826 tablet Substances 0.000 description 8
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
150000001721 carbon Chemical group 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
208000028017 Psychotic disease Diseases 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
108010037444 diisopropylglutathione ester Proteins 0.000 description 6
150000002431 hydrogen Chemical class 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
125000000815 N-oxide group Chemical group 0.000 description 5
230000008485 antagonism Effects 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
230000000144 pharmacologic effect Effects 0.000 description 5
239000000126 substance Substances 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
239000003480 eluent Substances 0.000 description 4
238000004811 liquid chromatography Methods 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
239000002858 neurotransmitter agent Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
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 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000000654 additive Substances 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
239000003420 antiserotonin agent Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
230000002093 peripheral effect Effects 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
239000000843 powder Substances 0.000 description 3
229930195734 saturated hydrocarbon Natural products 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
206010001488 Aggression Diseases 0.000 description 2
208000019901 Anxiety disease Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
208000020925 Bipolar disease Diseases 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
102000015554 Dopamine receptor Human genes 0.000 description 2
108050004812 Dopamine receptor Proteins 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 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
241001465754 Metazoa Species 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
239000000674 adrenergic antagonist Substances 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 2
230000036506 anxiety Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
238000009835 boiling Methods 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000003245 coal Substances 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
230000036461 convulsion Effects 0.000 description 2
239000013078 crystal Substances 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
KPTZZHXTMHWHSK-UYAOXDASSA-N ethyl (4ar,9bs)-5-benzyl-3,4,4a,9b-tetrahydro-1h-pyrido[4,3-b]indole-2-carboxylate Chemical compound C1([C@@H]2[C@H]3CCN(C2)C(=O)OCC)=CC=CC=C1N3CC1=CC=CC=C1 KPTZZHXTMHWHSK-UYAOXDASSA-N 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000011187 glycerol Nutrition 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
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
229940100688 oral solution Drugs 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
150000002978 peroxides Chemical class 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
229960003415 propylparaben Drugs 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
201000000980 schizophrenia Diseases 0.000 description 2
238000010956 selective crystallization Methods 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
239000012453 solvate Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
229930192474 thiophene Natural products 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
BPPMRCNUQCVVFJ-GXSJLCMTSA-N (4ar,9br)-2,3,4,4a,5,9b-hexahydro-1h-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2[C@H]2[C@H]1CCNC2 BPPMRCNUQCVVFJ-GXSJLCMTSA-N 0.000 description 1
DAFWBWMYCWYNEC-FUHWJXTLSA-N (4ar,9br)-2-benzyl-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indole Chemical compound C([C@H]1C2=CC=CC=C2N[C@@H]1CC1)N1CC1=CC=CC=C1 DAFWBWMYCWYNEC-FUHWJXTLSA-N 0.000 description 1
TYLIXOCIUJMGFC-PKOBYXMFSA-N (4ar,9br)-2-benzyl-8-methoxy-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indole Chemical compound C([C@H]1NC2=CC=C(C=C2[C@@H]1C1)OC)CN1CC1=CC=CC=C1 TYLIXOCIUJMGFC-PKOBYXMFSA-N 0.000 description 1
GEFKKHAFZOPSGA-GXSJLCMTSA-N (4ar,9br)-8-fluoro-2,3,4,4a,5,9b-hexahydro-1h-pyrido[4,3-b]indole Chemical compound C1CNC[C@H]2C3=CC(F)=CC=C3N[C@@H]21 GEFKKHAFZOPSGA-GXSJLCMTSA-N 0.000 description 1
DCTSSEIHVASKBC-DOTOQJQBSA-N (4ar,9br)-8-fluoro-5-(4-fluorophenyl)-1,2,3,4,4a,9b-hexahydropyrido[4,3-b]indole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(F)C=C2[C@@H]2CNCC[C@H]21 DCTSSEIHVASKBC-DOTOQJQBSA-N 0.000 description 1
PRTXTCNWQUOIIP-CMPLNLGQSA-N (4ar,9br)-8-methoxy-2,3,4,4a,5,9b-hexahydro-1h-pyrido[4,3-b]indole Chemical compound C1CNC[C@H]2C3=CC(OC)=CC=C3N[C@@H]21 PRTXTCNWQUOIIP-CMPLNLGQSA-N 0.000 description 1
NYGMREOWPIHEDP-SJLPKXTDSA-N (4ar,9bs)-5-benzyl-1,2,3,4,4a,9b-hexahydropyrido[4,3-b]indole Chemical compound C1([C@H]2CNCC[C@H]22)=CC=CC=C1N2CC1=CC=CC=C1 NYGMREOWPIHEDP-SJLPKXTDSA-N 0.000 description 1
JZNDLEDDYQQRAL-ZYHUDNBSSA-N (4ar,9bs)-5-methyl-1,2,3,4,4a,9b-hexahydropyrido[4,3-b]indole Chemical compound C12=CC=CC=C2N(C)[C@H]2[C@@H]1CNCC2 JZNDLEDDYQQRAL-ZYHUDNBSSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 1
OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 1
HCUARRIEZVDMPT-UHFFFAOYSA-M 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)[O-])=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-M 0.000 description 1
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
TWZCZLLZJDKWFN-UHFFFAOYSA-N 2-benzyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound C1CC=2NC3=CC=CC=C3C=2CN1CC1=CC=CC=C1 TWZCZLLZJDKWFN-UHFFFAOYSA-N 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
LFTGLYCNMGGMKL-UHFFFAOYSA-N 3-(2-chloroethyl)-2-methylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC=CN2C(=O)C(CCCl)=C(C)N=C21 LFTGLYCNMGGMKL-UHFFFAOYSA-N 0.000 description 1
102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 1
108091005479 5-HT2 receptors Proteins 0.000 description 1
SVZSNASRUSJMAF-UHFFFAOYSA-N 6-(2-chloroethyl)-7-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound O=C1C(CCCl)=C(C)N=C2SC=CN21 SVZSNASRUSJMAF-UHFFFAOYSA-N 0.000 description 1
CQXHBRCTUOFUJB-UHFFFAOYSA-N 6-[2-(8-fluoro-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indol-2-yl)ethyl]-7-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound N1C2=CC=C(F)C=C2C(C2)C1CCN2CCC(C1=O)=C(C)N=C2N1C=CS2 CQXHBRCTUOFUJB-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000020706 Autistic disease Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
206010020565 Hyperaemia Diseases 0.000 description 1
206010020772 Hypertension Diseases 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
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
244000171263 Ribes grossularia Species 0.000 description 1
235000002357 Ribes grossularia Nutrition 0.000 description 1
235000011034 Rubus glaucus Nutrition 0.000 description 1
244000235659 Rubus idaeus Species 0.000 description 1
235000009122 Rubus idaeus Nutrition 0.000 description 1
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000000695 adrenergic alpha-agonist Substances 0.000 description 1
230000016571 aggressive behavior Effects 0.000 description 1
208000012761 aggressive behavior Diseases 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000004974 alkaline earth metal peroxides Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000000561 anti-psychotic effect Effects 0.000 description 1
230000036528 appetite Effects 0.000 description 1
235000019789 appetite Nutrition 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
235000015895 biscuits Nutrition 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 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
ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
229940125758 compound 15 Drugs 0.000 description 1
229940126208 compound 22 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000000254 damaging effect Effects 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
229940075894 denatured ethanol Drugs 0.000 description 1
GYNPZALQDHAKME-DZGCQCFKSA-N diethyl (4ar,9br)-8-chloro-3,4,4a,9b-tetrahydro-1h-pyrido[4,3-b]indole-2,5-dicarboxylate Chemical compound C12=CC(Cl)=CC=C2N(C(=O)OCC)[C@H]2[C@H]1CN(C(=O)OCC)CC2 GYNPZALQDHAKME-DZGCQCFKSA-N 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000003210 dopamine receptor blocking agent Substances 0.000 description 1
239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
230000035622 drinking Effects 0.000 description 1
229940079593 drug Drugs 0.000 description 1
VBDDIOPVRQTWKP-DGCLKSJQSA-N ethyl (4ar,9bs)-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indole-2-carboxylate Chemical compound N1C2=CC=CC=C2[C@@H]2[C@H]1CCN(C(=O)OCC)C2 VBDDIOPVRQTWKP-DGCLKSJQSA-N 0.000 description 1
AKPNWVKYAAVIIB-UHFFFAOYSA-N ethyl 1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylate Chemical compound N1C2=CC=CC=C2C2=C1CCN(C(=O)OCC)C2 AKPNWVKYAAVIIB-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
150000002314 glycerols Chemical class 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
150000008282 halocarbons Chemical class 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
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical class C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
230000001077 hypotensive effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
150000004668 long chain fatty acids Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
208000001022 morbid obesity Diseases 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000001451 organic peroxides Chemical class 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
238000000053 physical method Methods 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Inorganic materials [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
239000001294 propane Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000008213 purified water Substances 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
JADFCQKRKICRKI-UHFFFAOYSA-N quinoline;sulfane Chemical compound S.N1=CC=CC2=CC=CC=C21 JADFCQKRKICRKI-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000000862 serotonergic effect Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
MDDPTCUZZASZIQ-UHFFFAOYSA-N tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] MDDPTCUZZASZIQ-UHFFFAOYSA-N 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- 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
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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

Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Indole Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO19985389A 1996-05-23 1998-11-19 Heksahydro-pyrido (4,3-B)indolderivater som antipsykotiske legemidler NO311724B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP96201450		1996-05-23
PCT/EP1997/002710 WO1997044040A1 (en)	1996-05-23	1997-05-15	Hexahydro-pyrido(4,3-b)indole derivatives as antipsychotic drugs

Publications (3)

Publication Number	Publication Date
NO985389D0 NO985389D0 (no)	1998-11-19
NO985389L NO985389L (no)	1999-01-20
NO311724B1 true NO311724B1 (no)	2002-01-14

Family

ID=8224021

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19985389A NO311724B1 (no)	1996-05-23	1998-11-19	Heksahydro-pyrido (4,3-B)indolderivater som antipsykotiske legemidler

Country Status (22)

Country	Link
US (1)	US6057325A (xx)
EP (1)	EP0902684B1 (xx)
JP (1)	JP2000510860A (xx)
CN (1)	CN1149996C (xx)
AT (1)	ATE236636T1 (xx)
AU (1)	AU714113B2 (xx)
CA (1)	CA2254755C (xx)
CY (1)	CY2381B1 (xx)
CZ (1)	CZ287961B6 (xx)
DE (1)	DE69720715T2 (xx)
DK (1)	DK0902684T3 (xx)
ES (1)	ES2196332T3 (xx)
IL (1)	IL127177A (xx)
MY (1)	MY125562A (xx)
NO (1)	NO311724B1 (xx)
NZ (1)	NZ332310A (xx)
PL (1)	PL187345B1 (xx)
PT (1)	PT902684E (xx)
SI (1)	SI0902684T1 (xx)
TW (1)	TW470745B (xx)
WO (1)	WO1997044040A1 (xx)
ZA (1)	ZA974470B (xx)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1136493A1 (en) *	2000-03-23	2001-09-26	Sanofi-Synthelabo	2-(Thienopyridinyl)pyrimidone, 2-(furopyridinyl)pyrimidone 2-(isoquinolinyl)pyrimidone, 2-(pyridoindolyl)pyrimidone and 2-(benzofuropyridinyl)pyrimidone derivatives
ATE306486T1 (de) *	2001-08-08	2005-10-15	Pharmacia & Upjohn Co Llc	Therapeutische 1h-pyrido(4,3-b)indole
PL377426A1 (pl) *	2002-12-19	2006-02-06	Bristol-Myers Squibb Company	Podstawione tricykliczne gamma-karboliny jako agoniści i antagoniści receptora serotoninowego
CN1882590B (zh) *	2003-09-17	2014-03-05	詹森药业有限公司	作为血清素受体调节剂的稠合杂环化合物
EP1944306A1 (en) *	2003-09-17	2008-07-16	Janssen Pharmaceutica, N.V.	Fused heterocyclic compounds as serotonin receptor modulators
CA2539426C (en) *	2003-09-17	2012-07-10	Janssen Pharmaceutica, Nv	Fused heterocyclic compounds
KR101168611B1 (ko)	2003-09-17	2012-08-03	얀센 파마슈티카 엔.브이.	세로토닌 수용체 조절자로서의 융합된 헤테로사이클릭 화합물
RU2338537C2 (ru) *	2006-01-25	2008-11-20	Сергей Олегович Бачурин	СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ
EP2175724A4 (en) *	2007-08-01	2010-09-15	Medivation Neurology Inc	METHOD AND COMPOSITIONS FOR TREATING SCHIZOPHRENIA USING ANTIPSYCHOTIC COMBINATION THERAPY
TWI482773B (zh)	2008-10-31	2015-05-01	Medivation Technologies Inc	氮呯并〔４，５－ｂ〕吲哚及使用方法
EP2346332A4 (en) *	2008-10-31	2012-08-08	Medivation Technologies Inc	PYRIDOÝ4,3-BINDOLES CONTAINING RIGID FRAGMENTS
IN2013MN01699A (xx)	2011-02-18	2015-06-12	Medivation Technologies Inc
WO2014031165A1 (en) *	2012-08-22	2014-02-27	Medivation Technologies, Inc.	Compounds and methods of treating diabetes

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AR205452A1 (es) *	1973-12-06	1976-05-07	Endo Lab	Metodo para preparar nuevos trans-2, 3, 4, 4a, 5, 9b-hexahidro-5-fenil-1h-pirido(4,3-b) indoles
US4337250A (en) *	1979-07-30	1982-06-29	Pfizer Inc.	Hexahydro-trans- and tetrahydropyridoindole neuroleptic agents

1997
- 1997-05-01 TW TW086105765A patent/TW470745B/zh not_active IP Right Cessation
- 1997-05-15 WO PCT/EP1997/002710 patent/WO1997044040A1/en not_active Application Discontinuation
- 1997-05-15 DE DE69720715T patent/DE69720715T2/de not_active Expired - Fee Related
- 1997-05-15 US US09/180,366 patent/US6057325A/en not_active Expired - Fee Related
- 1997-05-15 EP EP97924014A patent/EP0902684B1/en not_active Expired - Lifetime
- 1997-05-15 JP JP09541588A patent/JP2000510860A/ja not_active Ceased
- 1997-05-15 DK DK97924014T patent/DK0902684T3/da active
- 1997-05-15 ES ES97924014T patent/ES2196332T3/es not_active Expired - Lifetime
- 1997-05-15 CA CA002254755A patent/CA2254755C/en not_active Expired - Fee Related
- 1997-05-15 CZ CZ19983774A patent/CZ287961B6/cs not_active IP Right Cessation
- 1997-05-15 NZ NZ332310A patent/NZ332310A/xx unknown
- 1997-05-15 AT AT97924014T patent/ATE236636T1/de not_active IP Right Cessation
- 1997-05-15 IL IL12717797A patent/IL127177A/xx not_active IP Right Cessation
- 1997-05-15 AU AU29616/97A patent/AU714113B2/en not_active Ceased
- 1997-05-15 PT PT97924014T patent/PT902684E/pt unknown
- 1997-05-15 PL PL97330079A patent/PL187345B1/pl not_active IP Right Cessation
- 1997-05-15 CN CNB971948739A patent/CN1149996C/zh not_active Expired - Fee Related
- 1997-05-15 SI SI9730542T patent/SI0902684T1/xx unknown
- 1997-05-22 MY MYPI97002245A patent/MY125562A/en unknown
- 1997-05-22 ZA ZA974470A patent/ZA974470B/xx unknown
1998
- 1998-11-19 NO NO19985389A patent/NO311724B1/no unknown
2003
- 2003-11-04 CY CY0300075A patent/CY2381B1/xx unknown

Also Published As

Publication number	Publication date
WO1997044040A1 (en)	1997-11-27
DE69720715T2 (de)	2004-03-11
DK0902684T3 (da)	2004-03-29
NO985389L (no)	1999-01-20
EP0902684B1 (en)	2003-04-09
PT902684E (pt)	2003-08-29
PL187345B1 (pl)	2004-06-30
SI0902684T1 (en)	2003-10-31
ES2196332T3 (es)	2003-12-16
IL127177A (en)	2003-10-31
EP0902684A1 (en)	1999-03-24
JP2000510860A (ja)	2000-08-22
CN1149996C (zh)	2004-05-19
CA2254755C (en)	2007-01-16
ATE236636T1 (de)	2003-04-15
ZA974470B (en)	1998-11-23
IL127177A0 (en)	1999-09-22
US6057325A (en)	2000-05-02
AU714113B2 (en)	1999-12-16
CA2254755A1 (en)	1997-11-27
CZ377498A3 (cs)	1999-02-17
NO985389D0 (no)	1998-11-19
CY2381B1 (en)	2004-06-04
PL330079A1 (en)	1999-04-26
DE69720715D1 (en)	2003-05-15
CN1219875A (zh)	1999-06-16
TW470745B (en)	2002-01-01
AU2961697A (en)	1997-12-09
NZ332310A (en)	1999-08-30
CZ287961B6 (cs)	2001-03-14
MY125562A (en)	2006-08-30

Publication	Publication Date	Title
US20030064991A1 (en)	2003-04-03	Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor
NO301421B1 (no)	1997-10-27	Analogifremgangsmåte for fremstilling av terapeutisk aktive, heterocykliske aminer
CZ281676B6 (cs)	1996-12-11	1-piperazin-1,2-dihydroindenové deriváty, farmaceutické prostředky s jejich obsahem a použití uvedených látek pro výrobu farmaceutických prostředků
SK27196A3 (en)	1996-10-02	Bicyclic aromatic compounds as therapeutic agents
NO311724B1 (no)	2002-01-14	Heksahydro-pyrido (4,3-B)indolderivater som antipsykotiske legemidler
MXPA00007058A (es)	2002-04-24	Nuevos compuestos de -carbolina, un proceso para su preparacion y composiciones farmaceuticas que los contienen.
NZ203302A (en)	1986-08-08	Pyrazolo(4,3-c)pyridine derivatives,methods for their preparation and pharmaceutical compositions which contain them
MXPA05002743A (es)	2005-06-03	Derivados arilpiperazina de benzodioxanos con heterociclos fusionados antidepresivos.
NO129043B (xx)	1974-02-18
DE69829317T2 (de)	2006-04-06	Tetrahydrobenzindol-derivate
NO315236B1 (no)	2003-08-04	Tetrahydro gamma-karboliner, deres fremstilling og farmasöytiske sammensetninger inneholdende det samme
EP0808313B1 (en)	2003-08-13	Antipsychotic 4-(1h-indolyl-1-yl)-1-substituted piperidine derivatives
NO173058B (no)	1993-07-12	Analogifremgangsmaate for fremstilling av terapeutisk aktive kinolinderivater
IE66198B1 (en)	1995-12-13	Antipsychotic 3-piperazinylbenzazole derivatives
JP6267334B2 (ja)	2018-01-24	５−ｈｔ６拮抗薬としてのピロロキノリン誘導体、それらの製造方法および使用
JPS60188385A (ja)	1985-09-25	置換ヘキサヒドロアリ−ルキノリジン類
AU2002300094B2 (en)	2007-06-14	New octahydro-2H-pyrido[1,2-alpha]pyrazine compounds, a process for their preparation and pharmaceutical compositions containing them
NO300847B1 (no)	1997-08-04	Analogifremgangsmåte for fremstilling av terapeutisk aktive perhydro-1H-pyrido£1,2-a\|pyraziner
KR100539724B1 (ko)	2006-07-06	항정신병성약제로서의헥사하이드로-피리도(4,3-b)인돌유도체
RU2126005C1 (ru)	1999-02-10	3-{2-[4-(6-фторбензо[d]изоксазол-3-ил)-3,6-дигидро-2h-пиридин-1-ил]этил}-2 -метил- 6,7,8,9[-тетрагидропиридо{1,2-a] пиримидин-4-он и его фармацевтически приемлемые соли, способ его получения, способ получения соли 1-[2-(2-метил-4-оксо-6,7,8,9- тетрагидро-4h-пиридо[1,2-a]пиримидин-3-ил)этил]-4-(6-фторбензо[d]изоксазол -3- ил)пиридиния, фармацевтическая композиция
CN111386270B (zh)	2022-05-03	作为毒蕈碱m1受体正向别构调节剂的经取代氮杂环
EP0746556B1 (en)	2002-09-25	Tricyclic compounds having affinity for the 5-ht1a receptor
US20100311734A1 (en)	2010-12-09	Spiro Compounds Useful as Antagonists of the H1 Receptor
NO315001B1 (no)	2003-06-23	Farmasöytisk aktive substituerte dihydropyranopyridiner samt fremgangsmåteved fremstilling derav, hvor dihydropytanopyridinene harvaskokonstriktive egenskaper
BG64625B1 (bg)	2005-09-30	Бензотиено[3,2-c]пиридини, като алфа 2 - антагонисти