CA2037100C - Derives de substitution en 6 d'hexahydrobenz¢cd!indoles - Google Patents

Derives de substitution en 6 d'hexahydrobenz¢cd!indoles Download PDF

Info

Publication number: CA2037100C
Authority: CA; Canada
Prior art keywords: alkyl; hydrogen; compound; substituted; formula
Prior art date: 1990-02-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA 2037100

Other languages

English (en)

Other versions

CA2037100A1 (fr

Inventor

Michael E. Flaugh

Mark M. Foreman

Michael J. Martinelli

Thomas J. Kress

Marvin R. Leanna

Barry C. Peterson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1990-02-26

Filing date

1991-02-26

Publication date

2003-10-21

1990-02-26 Priority claimed from US07/482,811 external-priority patent/US5204340A/en

1991-02-26 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1991-08-27 Publication of CA2037100A1 publication Critical patent/CA2037100A1/fr

2003-10-21 Application granted granted Critical

2003-10-21 Publication of CA2037100C publication Critical patent/CA2037100C/fr

2011-02-26 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

150000002475 indoles Chemical class 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims description 123
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 119
229910052739 hydrogen Inorganic materials 0.000 claims description 97
239000001257 hydrogen Substances 0.000 claims description 97
150000002431 hydrogen Chemical group 0.000 claims description 55
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
125000003118 aryl group Chemical group 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 26
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
125000000753 cycloalkyl group Chemical group 0.000 claims description 22
125000003342 alkenyl group Chemical group 0.000 claims description 20
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 18
229910052760 oxygen Inorganic materials 0.000 claims description 18
239000001301 oxygen Substances 0.000 claims description 18
125000003107 substituted aryl group Chemical group 0.000 claims description 18
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 15
229910052757 nitrogen Inorganic materials 0.000 claims description 15
229910052717 sulfur Chemical group 0.000 claims description 15
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
239000011593 sulfur Chemical group 0.000 claims description 12
239000004480 active ingredient Substances 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
239000003054 catalyst Substances 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
230000000903 blocking effect Effects 0.000 claims description 8
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
229910052763 palladium Inorganic materials 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
-1 4-amino-6-substituted-hexahydrobenz[cd]indoles Chemical class 0.000 abstract description 43
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
230000004075 alteration Effects 0.000 abstract description 4
201000010099 disease Diseases 0.000 abstract description 4
102000017911 HTR1A Human genes 0.000 abstract description 3
101150015707 HTR1A gene Proteins 0.000 abstract description 3
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 54
238000000034 method Methods 0.000 description 44
239000000203 mixture Substances 0.000 description 40
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
239000000243 solution Substances 0.000 description 27
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 26
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 26
238000002360 preparation method Methods 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical group C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 18
230000000875 corresponding effect Effects 0.000 description 16
239000002904 solvent Substances 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
238000007327 hydrogenolysis reaction Methods 0.000 description 13
239000003921 oil Substances 0.000 description 13
239000000047 product Substances 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
239000003153 chemical reaction reagent Substances 0.000 description 12
150000001412 amines Chemical class 0.000 description 11
235000019439 ethyl acetate Nutrition 0.000 description 11
238000005481 NMR spectroscopy Methods 0.000 description 10
229920002472 Starch Polymers 0.000 description 10
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 10
229940093499 ethyl acetate Drugs 0.000 description 10
238000009472 formulation Methods 0.000 description 10
239000000543 intermediate Substances 0.000 description 10
235000019698 starch Nutrition 0.000 description 10
101150041968 CDC13 gene Proteins 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
239000008107 starch Substances 0.000 description 9
238000003786 synthesis reaction Methods 0.000 description 9
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
150000001414 amino alcohols Chemical class 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
150000003335 secondary amines Chemical class 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
230000027455 binding Effects 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
150000002118 epoxides Chemical class 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
239000000463 material Substances 0.000 description 6
150000004702 methyl esters Chemical class 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
230000000707 stereoselective effect Effects 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
239000003826 tablet Substances 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 5
230000006870 function Effects 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 5
229940076279 serotonin Drugs 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 description 4
MTSYZAHZABCWMS-UHFFFAOYSA-N 6-bromo-2,3-dihydro-1h-indole Chemical compound BrC1=CC=C2CCNC2=C1 MTSYZAHZABCWMS-UHFFFAOYSA-N 0.000 description 4
229920000168 Microcrystalline cellulose Polymers 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
229930006000 Sucrose Natural products 0.000 description 4
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 4
125000002252 acyl group Chemical group 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
235000010980 cellulose Nutrition 0.000 description 4
239000001913 cellulose Substances 0.000 description 4
229920002678 cellulose Polymers 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000003814 drug Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
235000019813 microcrystalline cellulose Nutrition 0.000 description 4
239000008108 microcrystalline cellulose Substances 0.000 description 4
229940016286 microcrystalline cellulose Drugs 0.000 description 4
210000003739 neck Anatomy 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000005720 sucrose Substances 0.000 description 4
235000002906 tartaric acid Nutrition 0.000 description 4
239000011975 tartaric acid Substances 0.000 description 4
238000005406 washing Methods 0.000 description 4
125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 3
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 3
KJLFFCRGGGXQKE-UHFFFAOYSA-N 1h-indole-6-carboxamide Chemical compound NC(=O)C1=CC=C2C=CNC2=C1 KJLFFCRGGGXQKE-UHFFFAOYSA-N 0.000 description 3
JWLQULBRUJIEHY-UHFFFAOYSA-N 2,3-dihydro-1h-indol-6-ol Chemical compound OC1=CC=C2CCNC2=C1 JWLQULBRUJIEHY-UHFFFAOYSA-N 0.000 description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 3
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 3
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
208000019901 Anxiety disease Diseases 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
230000036506 anxiety Effects 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000012267 brine Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
229910002091 carbon monoxide Inorganic materials 0.000 description 3
150000001733 carboxylic acid esters Chemical group 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
238000006073 displacement reaction Methods 0.000 description 3
239000012039 electrophile Substances 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
150000002476 indolines Chemical class 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
230000008569 process Effects 0.000 description 3
238000010926 purge Methods 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
238000000926 separation method Methods 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000000829 suppository Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 2
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
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KGCBZEKELZUOFI-UHFFFAOYSA-N 6-iodo-2,3-dihydro-1h-indole Chemical compound IC1=CC=C2CCNC2=C1 KGCBZEKELZUOFI-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
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KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000004417 unsaturated alkyl group Chemical group 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229940071104 xylenesulfonate Drugs 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

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Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CA 2037100 1990-02-26 1991-02-26 Derives de substitution en 6 d'hexahydrobenz¢cd!indoles Expired - Fee Related CA2037100C (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US07/482,811 US5204340A (en)	1989-04-11	1990-02-26	Tetrahydrobenz(c,d)indole serotonin agonists
US482,811		1990-02-26
US56798690A	1990-08-15	1990-08-15
US567,986		1990-08-15

Publications (2)

Publication Number	Publication Date
CA2037100A1 CA2037100A1 (fr)	1991-08-27
CA2037100C true CA2037100C (fr)	2003-10-21

Family

ID=27047420

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2037100 Expired - Fee Related CA2037100C (fr)	1990-02-26	1991-02-26	Derives de substitution en 6 d'hexahydrobenz¢cd!indoles

Country Status (1)

Country	Link
CA (1)	CA2037100C (fr)

1991
- 1991-02-26 CA CA 2037100 patent/CA2037100C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2037100A1 (fr)	1991-08-27

Legal Events

Date	Code	Title	Description
1998-02-19	EEER	Examination request
2008-02-26	MKLA	Lapsed

Publication	Publication Date	Title
US5244912A (en)	1993-09-14	6-heterocyclic-4-amino-1,3,4,5-tetrahydrobenz(cd)indoles and pharmaceutical use thereof
US5302612A (en)	1994-04-12	6-substituted-hexahydrobenz[cd]indoles
US5229410A (en)	1993-07-20	6-substituted-hexahydrobenz[cd]indoles
US5244911A (en)	1993-09-14	6-heterocyclic-4-amino-1,2,2a,3,4,5-hexahydrobenz(cd)indoles and pharmaceutical use thereof
EP0444854B1 (fr)	1996-09-25	Hexahydrobenz[cd]indoles substitués en 6
US5229409A (en)	1993-07-20	6-substituted-tetrahydrobenz[cd]indoles
CA2037100C (fr)	2003-10-21	Derives de substitution en 6 d'hexahydrobenz¢cd!indoles
US5665744A (en)	1997-09-09	6-heterocyclic-4-amino-1,2,2A,3,4,5-hexahydrobenzn [cd] indoles
KR0176247B1 (ko)	1999-03-20	6-치환된-헥사하이드로벤즈인돌
US5783590A (en)	1998-07-21	6-heterocyclic-4-amino-1,2,2A,3,4,5-hexahydrobenz CD!indoles
CA2049176A1 (fr)	1992-02-16	Hexahydrobenz [cd] indoles a substitution en 6