NO751055L - - Google Patents

Info

Publication number: NO751055L
Authority: NO; Norway
Prior art keywords: fluorophenyl; tetrahydro; fluoro; carboline; formula
Prior art date: 1974-04-01

Application number

NO751055A

Other languages

English (en)

Norwegian (no)

Inventor

J J Plattner

C A Harbert

J R Tretter

Welch W Mckowan

Original Assignee

Pfizer

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.)

1974-04-01

Filing date

1975-03-25

Publication date

1975-10-02

1974-04-01 Priority claimed from US456641A external-priority patent/US3925409A/en

1975-03-25 Application filed by Pfizer filed Critical Pfizer

1975-10-02 Publication of NO751055L publication Critical patent/NO751055L/no

Links

150000001875 compounds Chemical class 0.000 claims description 54
229910052731 fluorine Inorganic materials 0.000 claims description 41
238000000034 method Methods 0.000 claims description 38
229910052739 hydrogen Chemical group 0.000 claims description 34
239000001257 hydrogen Chemical group 0.000 claims description 32
238000006243 chemical reaction Methods 0.000 claims description 26
239000000460 chlorine Chemical group 0.000 claims description 24
239000011737 fluorine Substances 0.000 claims description 24
125000004432 carbon atom Chemical group C* 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 21
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 20
125000002947 alkylene group Chemical group 0.000 claims description 20
229910052801 chlorine Inorganic materials 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
-1 bromobenzene compound Chemical class 0.000 claims description 17
125000001153 fluoro group Chemical group F* 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 12
150000008064 anhydrides Chemical class 0.000 claims description 11
150000002576 ketones Chemical class 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
229910052794 bromium Inorganic materials 0.000 claims description 8
150000002431 hydrogen Chemical group 0.000 claims description 8
QARVLSVVCXYDNA-UHFFFAOYSA-N phenyl bromide Natural products BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims description 8
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
238000005917 acylation reaction Methods 0.000 claims description 6
125000001589 carboacyl group Chemical group 0.000 claims description 6
150000004820 halides Chemical class 0.000 claims description 6
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 claims description 6
230000010933 acylation Effects 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 4
150000001298 alcohols Chemical class 0.000 claims description 2
230000018044 dehydration Effects 0.000 claims description 2
238000006297 dehydration reaction Methods 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
230000007062 hydrolysis Effects 0.000 claims description 2
238000006460 hydrolysis reaction Methods 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
150000003333 secondary alcohols Chemical class 0.000 claims description 2
125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 claims 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 109
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 96
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 76
229910000041 hydrogen chloride Inorganic materials 0.000 description 76
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
229910001868 water Inorganic materials 0.000 description 51
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
239000000203 mixture Substances 0.000 description 36
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
238000004458 analytical method Methods 0.000 description 34
239000000047 product Substances 0.000 description 34
239000000243 solution Substances 0.000 description 33
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
239000002904 solvent Substances 0.000 description 19
239000000725 suspension Substances 0.000 description 19
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
239000003921 oil Substances 0.000 description 18
235000019198 oils Nutrition 0.000 description 18
229910052943 magnesium sulfate Inorganic materials 0.000 description 17
235000019341 magnesium sulphate Nutrition 0.000 description 17
239000002585 base Substances 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
229920006395 saturated elastomer Polymers 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
238000010992 reflux Methods 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
239000007787 solid Substances 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
239000012458 free base Substances 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000012043 crude product Substances 0.000 description 9
239000003480 eluent Substances 0.000 description 9
239000000284 extract Substances 0.000 description 9
239000007789 gas Substances 0.000 description 9
239000012266 salt solution Substances 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
229910000029 sodium carbonate Inorganic materials 0.000 description 9
238000003756 stirring Methods 0.000 description 9
KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
229940025084 amphetamine Drugs 0.000 description 8
239000002775 capsule Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
239000012442 inert solvent Substances 0.000 description 7
239000012280 lithium aluminium hydride Substances 0.000 description 7
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
230000029936 alkylation Effects 0.000 description 6
238000005804 alkylation reaction Methods 0.000 description 6
238000010438 heat treatment Methods 0.000 description 6
150000002475 indoles Chemical class 0.000 description 6
150000004031 phenylhydrazines Chemical class 0.000 description 6
230000001624 sedative effect Effects 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
239000000538 analytical sample Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000003814 drug Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
239000000932 sedative agent Substances 0.000 description 5
PBUHAWCPUJZXSL-UHFFFAOYSA-N 7-fluoro-4-(4-fluorophenyl)-2,3-dihydro-1h-pyrrolo[3,4-b]indole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(F)C=C2C2=C1CNC2 PBUHAWCPUJZXSL-UHFFFAOYSA-N 0.000 description 4
239000007818 Grignard reagent Substances 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000002168 alkylating agent Substances 0.000 description 4
229940100198 alkylating agent Drugs 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
150000007857 hydrazones Chemical class 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
AIKRNPPDTQIQIZ-UHFFFAOYSA-N pyrrolo[3,4-b]indole Chemical group C1=CC=C2C3=CN=CC3=NC2=C1 AIKRNPPDTQIQIZ-UHFFFAOYSA-N 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
239000003204 tranquilizing agent Substances 0.000 description 4
230000002936 tranquilizing effect Effects 0.000 description 4
AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
MDAGIYDZFPGBEP-UHFFFAOYSA-N 4-[7-fluoro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indol-2-yl]-1-(4-fluorophenyl)butan-1-ol Chemical compound C=1C=C(F)C=CC=1C(O)CCCN(C1)CC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 MDAGIYDZFPGBEP-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
238000003747 Grignard reaction Methods 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
239000012346 acetyl chloride Substances 0.000 description 3
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
238000006254 arylation reaction Methods 0.000 description 3
RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 3
239000003610 charcoal Substances 0.000 description 3
239000003153 chemical reaction reagent 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
238000001816 cooling Methods 0.000 description 3
NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 3
150000004795 grignard reagents Chemical class 0.000 description 3
238000001819 mass spectrum Methods 0.000 description 3
229910052987 metal hydride Inorganic materials 0.000 description 3
150000004681 metal hydrides Chemical class 0.000 description 3
229940067157 phenylhydrazine Drugs 0.000 description 3
238000000746 purification Methods 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
229940125723 sedative agent Drugs 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
238000001665 trituration Methods 0.000 description 3
YQVZREHUWCCHHX-UHFFFAOYSA-N (4-chlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Cl)C=C1 YQVZREHUWCCHHX-UHFFFAOYSA-N 0.000 description 2
REUPXULKSZESBY-UHFFFAOYSA-N 1-[7-fluoro-4-(4-fluorophenyl)-2,3-dihydro-1h-pyrrolo[3,4-b]indol-1-yl]-3,3-dimethylbutan-1-one Chemical compound CC(C)(C)CC(=O)C1NCC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 REUPXULKSZESBY-UHFFFAOYSA-N 0.000 description 2
UMTDBQHJIKJUGZ-UHFFFAOYSA-N 4-[7-fluoro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indol-2-yl]-1-(4-fluorophenyl)butan-1-one;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C(=O)CCCN1CC(C=2C(=CC=C(F)C=2)N2C=3C=CC(F)=CC=3)=C2C1 UMTDBQHJIKJUGZ-UHFFFAOYSA-N 0.000 description 2
TZWSURDURFBLQE-UHFFFAOYSA-N 4-[8-chloro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indol-2-yl]-1-(4-fluorophenyl)butan-1-ol;hydrochloride Chemical compound Cl.C=1C=C(F)C=CC=1C(O)CCCN(C1)CC2=C1C1=C(Cl)C=CC=C1N2C1=CC=C(F)C=C1 TZWSURDURFBLQE-UHFFFAOYSA-N 0.000 description 2
RUWYUKDWFTUUJZ-UHFFFAOYSA-N 7-fluoro-4-(4-fluorophenyl)-2,3-dihydro-1h-pyrrolo[3,4-b]indole;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1N1C2=CC=C(F)C=C2C2=C1CNC2 RUWYUKDWFTUUJZ-UHFFFAOYSA-N 0.000 description 2
HZZHEIMZMCKOLL-UHFFFAOYSA-N 7-fluoro-4-(4-fluorophenyl)-2-(3-methylbutyl)-1,3-dihydropyrrolo[3,4-b]indole hydrochloride Chemical compound Cl.C1N(CCC(C)C)CC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 HZZHEIMZMCKOLL-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
101001066681 Homo sapiens Integrase Proteins 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
102100034353 Integrase Human genes 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
230000006399 behavior Effects 0.000 description 2
MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 2
230000000973 chemotherapeutic effect Effects 0.000 description 2
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000000084 colloidal system Substances 0.000 description 2
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
238000010828 elution Methods 0.000 description 2
PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
239000012259 ether extract Substances 0.000 description 2
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
LUBGFMZTGFXIIN-UHFFFAOYSA-N ethyl 4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)CC1 LUBGFMZTGFXIIN-UHFFFAOYSA-N 0.000 description 2
JZKXHUGBKHTPCL-UHFFFAOYSA-N ethyl 7-fluoro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indole-2-carboxylate Chemical compound C1N(C(=O)OCC)CC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 JZKXHUGBKHTPCL-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
150000005171 halobenzenes Chemical class 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
239000012264 purified product Substances 0.000 description 2
230000004044 response Effects 0.000 description 2
239000000523 sample Substances 0.000 description 2
239000008159 sesame oil Substances 0.000 description 2
235000011803 sesame oil Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
239000011343 solid material Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

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

NO751055A 1974-04-01 1975-03-25 NO751055L (pt)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US45664074A	1974-04-01	1974-04-01
US456641A US3925409A (en)	1974-04-01	1974-04-01	4-Aryl-1,2,3,4-tetrahydropyrrolo{8 3,4-b{9 indoles

Publications (1)

Publication Number	Publication Date
NO751055L true NO751055L (pt)	1975-10-02

Family

ID=27038317

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO751055A NO751055L (pt)	1974-04-01	1975-03-25

Country Status (15)

Country	Link
JP (1)	JPS587635B2 (pt)
AR (2)	AR206812A1 (pt)
AU (1)	AU7955975A (pt)
DD (1)	DD118879A5 (pt)
DE (1)	DE2514084A1 (pt)
DK (2)	DK130575A (pt)
ES (3)	ES436157A1 (pt)
FI (1)	FI750940A (pt)
FR (1)	FR2265368A1 (pt)
IL (1)	IL46925A0 (pt)
LU (1)	LU72182A1 (pt)
NL (1)	NL7503700A (pt)
NO (1)	NO751055L (pt)
RO (1)	RO72884A (pt)
SE (2)	SE423630B (pt)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4224329A (en) *	1979-01-23	1980-09-23	Pfizer Inc.	2-Substituted-trans-5-aryl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indoles
US4451655A (en) *	1982-05-17	1984-05-29	Pfizer Inc.	Process for preparing carboline derivatives and compounds used in their preparation
KR20060093139A (ko) *	1998-12-21	2006-08-23	얀센 파마슈티카 엔.브이.	α2-길항제로서의 벤즈이속사졸 및 페논
RU2320662C1 (ru) *	2006-08-24	2008-03-27	Андрей Александрович Иващенко	ЗАМЕЩЕННЫЕ ПИРРОЛО[4,3-b]ИНДОЛЫ, КОМБИНАТОРНАЯ И ФОКУСИРОВАННАЯ БИБЛИОТЕКИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ
RU2591194C2 (ru) *	2010-04-22	2016-07-10	Интра-Селлулар Терапиз, Инк.	Органические соединения

1975
- 1975-01-01 AR AR258188A patent/AR206812A1/es active
- 1975-01-01 AR AR261449A patent/AR207799A1/es active
- 1975-03-14 SE SE7502927A patent/SE423630B/xx unknown
- 1975-03-25 IL IL46925A patent/IL46925A0/xx unknown
- 1975-03-25 NO NO751055A patent/NO751055L/no unknown
- 1975-03-26 AU AU79559/75A patent/AU7955975A/en not_active Expired
- 1975-03-26 DK DK130575A patent/DK130575A/da not_active Application Discontinuation
- 1975-03-27 NL NL7503700A patent/NL7503700A/xx not_active Application Discontinuation
- 1975-03-27 FI FI750940A patent/FI750940A/fi not_active Application Discontinuation
- 1975-03-29 DE DE19752514084 patent/DE2514084A1/de not_active Ceased
- 1975-03-31 ES ES436157A patent/ES436157A1/es not_active Expired
- 1975-04-01 JP JP50040224A patent/JPS587635B2/ja not_active Expired
- 1975-04-01 LU LU72182A patent/LU72182A1/xx unknown
- 1975-04-01 FR FR7510139A patent/FR2265368A1/fr active Granted
- 1975-04-01 DD DD185114A patent/DD118879A5/xx unknown
- 1975-04-01 RO RO7581868A patent/RO72884A/ro unknown
1976
- 1976-11-30 ES ES453788A patent/ES453788A1/es not_active Expired
- 1976-11-30 ES ES453787A patent/ES453787A1/es not_active Expired
1978
- 1978-05-01 DK DK187878A patent/DK187878A/da not_active Application Discontinuation
1982
- 1982-01-07 SE SE8200047A patent/SE8200047L/sv not_active Application Discontinuation

Also Published As

Publication number	Publication date
AR206812A1 (es)	1976-08-23
ES436157A1 (es)	1977-04-16
FI750940A (pt)	1975-10-02
JPS587635B2 (ja)	1983-02-10
RO72884A (ro)	1983-08-03
SE7502927L (pt)	1975-10-02
IL46925A0 (en)	1975-05-22
ES453788A1 (es)	1978-01-01
FR2265368B1 (pt)	1978-07-28
AR207799A1 (es)	1976-10-29
DK130575A (pt)	1975-10-02
SE423630B (sv)	1982-05-17
JPS50140494A (pt)	1975-11-11
NL7503700A (nl)	1975-10-03
RO72884B (ro)	1983-07-30
DK187878A (da)	1978-05-01
DD118879A5 (pt)	1976-03-20
DE2514084A1 (de)	1975-11-20
FR2265368A1 (en)	1975-10-24
LU72182A1 (pt)	1976-03-02
AU7955975A (en)	1976-09-30
ES453787A1 (es)	1978-01-01
SE8200047L (sv)	1982-01-07

Publication	Publication Date	Title
EP0054507B1 (en)	1988-02-17	3-substituted beta-carbolines, process for their production and compositions containing them
US4487929A (en)	1984-12-11	Intermediates for pyrazolopyridazine derivatives
EP0248523B1 (en)	1991-10-16	Pyrazoles
US5602152A (en)	1997-02-11	Benzoxepines
RO117917B1 (ro)	2002-09-30	Derivati de imidazopiridina, procedee de obtinere si produs medicamentos
NO823775L (no)	1983-05-13	3-(1-substituert-4-piperidyl)-1,2-benzisoksazoler, fremgangsmaate til deres fremstilling, farmasoeytisk blanding inneholdende disse og deres bruk som legemidler
KR960011775B1 (ko)	1996-08-30	새로운 피롤 유도체, 이들의 제조방법 및 이들을 포함하는 약제학적 조성물
HU190984B (en)	1986-12-28	Process for producing new furo-, thieno- or pinolo-azepin derivatives
RU2114833C1 (ru)	1998-07-10	Арил-конденсированные 2,4-диазепиновые соединения, промежуточные продукты, антиаритмический агент и композиция
US4277476A (en)	1981-07-07	Derivatives of fluorenes and fluoranthenes and process for their preparation
EP0173279B1 (en)	1989-08-23	2-(3,5-dialkyl-4-hydroxyphenyl)indole derivatives
US4329467A (en)	1982-05-11	Phenyl-quinolizidines
NO751055L (pt)	1975-10-02
NZ204369A (en)	1986-09-10	Piperazine derivatives,their production,and pharmaceutical compositions which contain them
US4442102A (en)	1984-04-10	1,5-Diphenylpyrazolin-3-one compounds, process and intermediates for preparation thereof and pharmaceutical compositions containing same
JPS6026115B2 (ja)	1985-06-21	オキサジアゾロピリミジン誘導体
NZ202045A (en)	1986-03-14	Benzisoxazole derivatives and pharmaceutical compositions
HU191167B (en)	1987-01-28	Process for preparing 2-hydroxymethyl-1,4-dihydro-pyridine-3-carboxylic acid lactones and pharmaceutical compositions containing thereof
NO852663L (no)	1986-01-06	Fremgangsmaate ved fremstilling av 3-aminocarbonylmethoxy-5-fenylpyrazol-forbindelser.
US3753992A (en)	1973-08-21	Process and intermediates for quinine,quinidine and derivatives thereof
US4482714A (en)	1984-11-13	Pyrazino[2',3'-3,4]pyrido[1,2-a]indole derivatives
NO157578B (no)	1988-01-04	Analogifremgangsmaate ved fremstilling av terapeutisk aktive imidazo(1,2-a)kinolinderivater
US5310750A (en)	1994-05-10	Heterocyclic compounds useful as α2 -adrenoceptor antagonists
US4777181A (en)	1988-10-11	Alpha-2-antagonistic substituted 4-fluoro-isoindolines
NO742929L (pt)	1975-04-07