OA10502A - Indole derivatives as 5-ht receptor antagonist - Google Patents

Indole derivatives as 5-ht receptor antagonist Download PDF

Info

Publication number: OA10502A
Authority: OA; OAPI
Prior art keywords: methoxy; pyrid; pyridyl; phenyl; trifluoromethyl
Prior art date: 1995-02-02

Application number

OA70058A

Other languages

English (en)

Inventor

Laramie Mary Gaster

Paul Adrian Wyman

Keith Raymond Mulholland

David Thomas Davies

David Malcolm Duckworth

Ian Thomson Forbes

Graham Elgin Jones

Original Assignee

Smithkline Beecham Plc

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.)

1995-02-02

Filing date

1997-08-01

Publication date

2002-04-12

1995-02-02 Priority claimed from GBGB9502052.5A external-priority patent/GB9502052D0/en

1995-04-25 Priority claimed from GBGB9508327.5A external-priority patent/GB9508327D0/en

1995-05-03 Priority claimed from GBGB9508967.8A external-priority patent/GB9508967D0/en

1995-08-17 Priority claimed from GBGB9516845.6A external-priority patent/GB9516845D0/en

1995-08-26 Priority claimed from GBGB9517542.8A external-priority patent/GB9517542D0/en

1995-09-12 Priority claimed from GBGB9518574.0A external-priority patent/GB9518574D0/en

1997-08-01 Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc

2002-04-12 Publication of OA10502A publication Critical patent/OA10502A/en

Links

229940127239 5 Hydroxytryptamine receptor antagonist Drugs 0.000 title description 2
239000003420 antiserotonin agent Substances 0.000 title description 2
150000002475 indoles Chemical class 0.000 title description 2
229940054051 antipsychotic indole derivative Drugs 0.000 title 1
239000000203 mixture Substances 0.000 claims abstract description 81
238000000034 method Methods 0.000 claims abstract description 66
150000001875 compounds Chemical class 0.000 claims description 154
125000000217 alkyl group Chemical group 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
230000008878 coupling Effects 0.000 claims description 5
238000010168 coupling process Methods 0.000 claims description 5
238000005859 coupling reaction Methods 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 1
235000019256 formaldehyde Nutrition 0.000 claims 1
125000000524 functional group Chemical group 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 19
208000015114 central nervous system disease Diseases 0.000 abstract description 4
208000019901 Anxiety disease Diseases 0.000 abstract description 3
230000036506 anxiety Effects 0.000 abstract description 3
230000000144 pharmacologic effect Effects 0.000 abstract description 3
150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 163
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 120
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 78
239000007787 solid Substances 0.000 description 78
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
239000000243 solution Substances 0.000 description 64
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 42
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
MCSWKSCZARDPJX-UHFFFAOYSA-N 5-methoxy-6-(trifluoromethyl)-2,3-dihydro-1h-indole Chemical compound C1=C(C(F)(F)F)C(OC)=CC2=C1NCC2 MCSWKSCZARDPJX-UHFFFAOYSA-N 0.000 description 38
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
-1 SCF3 Chemical group 0.000 description 31
229940093499 ethyl acetate Drugs 0.000 description 31
235000019439 ethyl acetate Nutrition 0.000 description 31
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 27
239000008186 active pharmaceutical agent Substances 0.000 description 24
229910052786 argon Inorganic materials 0.000 description 21
239000000047 product Substances 0.000 description 21
238000010992 reflux Methods 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
239000002253 acid Substances 0.000 description 17
239000003208 petroleum Substances 0.000 description 17
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
229960001866 silicon dioxide Drugs 0.000 description 17
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 16
239000000284 extract Substances 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
235000011121 sodium hydroxide Nutrition 0.000 description 14
238000001816 cooling Methods 0.000 description 13
238000001914 filtration Methods 0.000 description 13
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 13
239000000725 suspension Substances 0.000 description 13
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 11
239000011734 sodium Substances 0.000 description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 10
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 10
239000003921 oil Substances 0.000 description 10
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 10
229940083608 sodium hydroxide Drugs 0.000 description 10
238000001035 drying Methods 0.000 description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
239000000377 silicon dioxide Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
DVFKRWUIYPFWHQ-UHFFFAOYSA-N 5-methylsulfanyl-6-(trifluoromethyl)-2,3-dihydro-1h-indole Chemical compound C1=C(C(F)(F)F)C(SC)=CC2=C1NCC2 DVFKRWUIYPFWHQ-UHFFFAOYSA-N 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
208000035475 disorder Diseases 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
125000004076 pyridyl group Chemical group 0.000 description 8
235000002639 sodium chloride Nutrition 0.000 description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
239000012043 crude product Substances 0.000 description 7
125000000623 heterocyclic group Chemical group 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
125000004414 alkyl thio group Chemical group 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
229910052736 halogen Inorganic materials 0.000 description 6
150000002367 halogens Chemical class 0.000 description 6
235000011167 hydrochloric acid Nutrition 0.000 description 6
229960000443 hydrochloric acid Drugs 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
150000003839 salts Chemical class 0.000 description 6
235000017550 sodium carbonate Nutrition 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
229940001593 sodium carbonate Drugs 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000003981 vehicle Substances 0.000 description 6
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
239000012267 brine Substances 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
239000008367 deionised water Substances 0.000 description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
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 5
CGUOPPPIULULIN-UHFFFAOYSA-N 2-pyridin-3-yloxypyridin-4-amine Chemical compound NC1=CC=NC(OC=2C=NC=CC=2)=C1 CGUOPPPIULULIN-UHFFFAOYSA-N 0.000 description 4
UQIRNFWEYGHLFN-UHFFFAOYSA-N 3-[[5-methylsulfanyl-6-(trifluoromethyl)-2,3-dihydroindole-1-carbonyl]amino]benzoic acid Chemical compound C1=2C=C(C(F)(F)F)C(SC)=CC=2CCN1C(=O)NC1=CC=CC(C(O)=O)=C1 UQIRNFWEYGHLFN-UHFFFAOYSA-N 0.000 description 4
CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 4
DZEIKJMNXHOFHL-UHFFFAOYSA-N 3-pyrimidin-5-ylaniline Chemical compound NC1=CC=CC(C=2C=NC=NC=2)=C1 DZEIKJMNXHOFHL-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 4
MYASECUWWGFQOJ-UHFFFAOYSA-N phenyl n-(4-tert-butyl-3-pyridin-3-ylphenyl)carbamate Chemical compound C1=C(C=2C=NC=CC=2)C(C(C)(C)C)=CC=C1NC(=O)OC1=CC=CC=C1 MYASECUWWGFQOJ-UHFFFAOYSA-N 0.000 description 4
SDBPWHDOWAKIJH-UHFFFAOYSA-N phenyl n-(6-pyridin-3-ylpyridin-3-yl)carbamate Chemical compound C=1C=CC=CC=1OC(=O)NC(C=N1)=CC=C1C1=CC=CN=C1 SDBPWHDOWAKIJH-UHFFFAOYSA-N 0.000 description 4
239000000843 powder Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
ASXFMIDIRZPCGK-UHFFFAOYSA-N (4-methylpyridin-3-yl)boronic acid Chemical compound CC1=CC=NC=C1B(O)O ASXFMIDIRZPCGK-UHFFFAOYSA-N 0.000 description 3
JZIGUWAAZINEDW-UHFFFAOYSA-N 4-nitro-1-oxido-2-pyridin-3-yloxypyridin-1-ium Chemical compound [O-][N+](=O)C1=CC=[N+]([O-])C(OC=2C=NC=CC=2)=C1 JZIGUWAAZINEDW-UHFFFAOYSA-N 0.000 description 3
DZNUXAXDALUDBZ-UHFFFAOYSA-N 5-(2,6-difluorophenyl)pyridine-3-carbonyl azide Chemical compound FC1=CC=CC(F)=C1C1=CN=CC(C(=O)N=[N+]=[N-])=C1 DZNUXAXDALUDBZ-UHFFFAOYSA-N 0.000 description 3
HRALXSSCXYCKIN-UHFFFAOYSA-N 7-pyridin-3-yl-2,3-dihydro-1-benzofuran-5-amine Chemical compound C=1C(N)=CC=2CCOC=2C=1C1=CC=CN=C1 HRALXSSCXYCKIN-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
239000005864 Sulphur Chemical group 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
239000006071 cream Substances 0.000 description 3
125000004093 cyano group Chemical group *C#N 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 3
BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 3
VHHSXTMSVQGBCZ-UHFFFAOYSA-N phenyl n-(3-fluoro-4-methoxy-5-pyridin-3-ylphenyl)carbamate Chemical compound C1=C(C=2C=NC=CC=2)C(OC)=C(F)C=C1NC(=O)OC1=CC=CC=C1 VHHSXTMSVQGBCZ-UHFFFAOYSA-N 0.000 description 3
RFEBPXVCSFLNGT-UHFFFAOYSA-N phenyl n-(4-chloro-3-pyridin-3-ylphenyl)carbamate Chemical compound C1=C(C=2C=NC=CC=2)C(Cl)=CC=C1NC(=O)OC1=CC=CC=C1 RFEBPXVCSFLNGT-UHFFFAOYSA-N 0.000 description 3
ROLBIVHOVWGRPJ-UHFFFAOYSA-N phenyl n-[3-(4-methylpyridin-3-yl)phenyl]carbamate Chemical compound CC1=CC=NC=C1C1=CC=CC(NC(=O)OC=2C=CC=CC=2)=C1 ROLBIVHOVWGRPJ-UHFFFAOYSA-N 0.000 description 3
235000015320 potassium carbonate Nutrition 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
238000011321 prophylaxis Methods 0.000 description 3
ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 3
125000000714 pyrimidinyl group Chemical group 0.000 description 3
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
239000001117 sulphuric acid Substances 0.000 description 3
235000011149 sulphuric acid Nutrition 0.000 description 3
239000003826 tablet Substances 0.000 description 3
238000001665 trituration Methods 0.000 description 3
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
RNTCWULFNYNFGI-UHFFFAOYSA-N 1-(2,3-dihydroindol-1-yl)ethanone Chemical compound C1=CC=C2N(C(=O)C)CCC2=C1 RNTCWULFNYNFGI-UHFFFAOYSA-N 0.000 description 2
JULUAUZIVDSBND-UHFFFAOYSA-N 1-pyridin-4-ylindol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1C1=CC=NC=C1 JULUAUZIVDSBND-UHFFFAOYSA-N 0.000 description 2
IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 2
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical class N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
ROXMEGSVJDLDHD-UHFFFAOYSA-N 3-amino-n-pyridin-3-ylbenzamide Chemical compound NC1=CC=CC(C(=O)NC=2C=NC=CC=2)=C1 ROXMEGSVJDLDHD-UHFFFAOYSA-N 0.000 description 2
NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 2
NQPTZDNPCHRUKQ-UHFFFAOYSA-N 3-fluoro-5-pyrimidin-5-ylbenzoyl azide Chemical compound FC1=CC(C(=O)N=[N+]=[N-])=CC(C=2C=NC=NC=2)=C1 NQPTZDNPCHRUKQ-UHFFFAOYSA-N 0.000 description 2
SUFBXXRIPSNILO-UHFFFAOYSA-N 3-nitro-n-pyridin-3-ylbenzamide Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)NC=2C=NC=CC=2)=C1 SUFBXXRIPSNILO-UHFFFAOYSA-N 0.000 description 2
YTJQJGKMRLQBJP-UHFFFAOYSA-N 3-pyridin-3-ylaniline Chemical compound NC1=CC=CC(C=2C=NC=CC=2)=C1 YTJQJGKMRLQBJP-UHFFFAOYSA-N 0.000 description 2
BDSBSHZVSVKIHM-UHFFFAOYSA-N 3-pyridin-4-ylaniline Chemical compound NC1=CC=CC(C=2C=CN=CC=2)=C1 BDSBSHZVSVKIHM-UHFFFAOYSA-N 0.000 description 2
GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 2
NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 2
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Classifications

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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

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

OA70058A 1995-02-02 1997-08-01 Indole derivatives as 5-ht receptor antagonist OA10502A (en)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
GBGB9502052.5A GB9502052D0 (en)	1995-02-02	1995-02-02	Novel compounds
GBGB9508327.5A GB9508327D0 (en)	1995-04-25	1995-04-25	Novel compounds
GBGB9508967.8A GB9508967D0 (en)	1995-05-03	1995-05-03	Novel compounds
GBGB9516845.6A GB9516845D0 (en)	1995-08-17	1995-08-17	Novel compounds
GBGB9517542.8A GB9517542D0 (en)	1995-08-26	1995-08-26	Novel compounds
GBGB9518574.0A GB9518574D0 (en)	1995-09-12	1995-09-12	Novel compounds

Publications (1)

Publication Number	Publication Date
OA10502A true OA10502A (en)	2002-04-12

Family

ID=27547235

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA70058A OA10502A (en)	1995-02-02	1997-08-01	Indole derivatives as 5-ht receptor antagonist

Country Status (33)

Country	Link
US (3)	US5990133A (de)
EP (1)	EP0808312B1 (de)
JP (1)	JPH10513442A (de)
KR (1)	KR19980701879A (de)
CN (1)	CN1151147C (de)
AP (1)	AP657A (de)
AR (1)	AR002705A1 (de)
AT (1)	ATE197300T1 (de)
AU (1)	AU699727B2 (de)
BG (1)	BG101806A (de)
BR (1)	BR9607016A (de)
CA (1)	CA2212061A1 (de)
CZ (1)	CZ294097B6 (de)
DE (1)	DE69610822T2 (de)
DK (1)	DK0808312T3 (de)
EA (1)	EA000304B1 (de)
ES (1)	ES2151652T3 (de)
FI (1)	FI973205A7 (de)
GR (1)	GR3035075T3 (de)
HU (1)	HU223601B1 (de)
IL (1)	IL116998A (de)
MA (1)	MA23792A1 (de)
MY (1)	MY132229A (de)
NO (1)	NO313520B1 (de)
NZ (1)	NZ301265A (de)
OA (1)	OA10502A (de)
PL (1)	PL184490B1 (de)
PT (1)	PT808312E (de)
RO (1)	RO115522B1 (de)
SI (1)	SI0808312T1 (de)
SK (1)	SK103897A3 (de)
TR (1)	TR199700749T1 (de)
WO (1)	WO1996023783A1 (de)

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GB9517559D0 (en) *	1995-08-26	1995-10-25	Smithkline Beecham Plc	Novel compounds
GB9607219D0 (en) *	1996-04-04	1996-06-12	Smithkline Beecham Plc	Novel compounds
GB9612885D0 (en)	1996-06-20	1996-08-21	Smithkline Beecham Plc	Novel compounds
GB9612883D0 (en)	1996-06-20	1996-08-21	Smithkline Beecham Plc	Novel compounds
US6191131B1 (en)	1997-07-23	2001-02-20	Dupont Pharmaceuticals Company	Azolo triazines and pyrimidines
US6124289A (en) *	1996-07-24	2000-09-26	Dupont Pharmaceuticals Co.	Azolo triazines and pyrimidines
US6060478A (en) *	1996-07-24	2000-05-09	Dupont Pharmaceuticals	Azolo triazines and pyrimidines
US6313124B1 (en)	1997-07-23	2001-11-06	Dupont Pharmaceuticals Company	Tetrazine bicyclic compounds
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GB9710523D0 (en) *	1997-05-23	1997-07-16	Smithkline Beecham Plc	Novel compounds
AU751139B2 (en)	1997-10-13	2002-08-08	Astellas Pharma Inc.	Amide derivative
US6022884A (en) *	1997-11-07	2000-02-08	Amgen Inc.	Substituted pyridine compounds and methods of use
WO1999043650A2 (en) *	1998-02-25	1999-09-02	Smithkline Beecham Plc	Process(es) for the preparation of 6-trifluoromethyl-indoline derivatives
US6107324A (en) *	1998-04-14	2000-08-22	Arena Pharmaceuticals Inc.	5-HT2A receptor inverse agonists
US6140509A (en) *	1998-06-26	2000-10-31	Arena Pharmaceuticals, Inc.	Non-endogenous, constitutively activated human serotonin receptors and small molecule modulators thereof
US6150393A (en) *	1998-12-18	2000-11-21	Arena Pharmaceuticals, Inc.	Small molecule modulators of non-endogenous, constitutively activated human serotonin receptors
UA71971C2 (en)	1999-06-04	2005-01-17	Agoron Pharmaceuticals Inc	Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases
US7141581B2 (en)	1999-07-02	2006-11-28	Agouron Pharmaceuticals, Inc.	Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
TWI262914B (en)	1999-07-02	2006-10-01	Agouron Pharma	Compounds and pharmaceutical compositions for inhibiting protein kinases
BR0012934A (pt) *	1999-08-04	2003-07-29	Icagen Inc	Processos para a redução de dor e de ansiedade
AUPQ319899A0 (en) *	1999-10-01	1999-10-28	Fujisawa Pharmaceutical Co., Ltd.	Amide compounds
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US6235758B1 (en)	2001-05-22
EP0808312A1 (de)	1997-11-26
MA23792A1 (fr)	1996-10-01
MY132229A (en)	2007-09-28
HU223601B1 (hu)	2004-10-28
HUP9901115A3 (en)	2000-02-28
HUP9901115A2 (hu)	1999-07-28
SK103897A3 (en)	1998-02-04
TR199700749T1 (xx)	1998-02-21
DK0808312T3 (da)	2001-02-12
PL321706A1 (en)	1997-12-22
WO1996023783A1 (en)	1996-08-08
AU4664696A (en)	1996-08-21
CA2212061A1 (en)	1996-08-08
IL116998A (en)	2001-08-08
NO313520B1 (no)	2002-10-14
IL116998A0 (en)	1996-09-12
SI0808312T1 (de)	2001-02-28
FI973205L (fi)	1997-10-01
AP657A (en)	1998-08-06
AR002705A1 (es)	1998-04-29
ES2151652T3 (es)	2001-01-01
CZ244597A3 (cs)	1998-09-16
EA199700156A1 (ru)	1997-12-30
US6638953B2 (en)	2003-10-28
KR19980701879A (ko)	1998-06-25
CN1179156A (zh)	1998-04-15
BG101806A (bg)	1998-04-30
US5990133A (en)	1999-11-23
AU699727B2 (en)	1998-12-10
NZ301265A (en)	1998-12-23
GR3035075T3 (en)	2001-03-30
BR9607016A (pt)	1997-10-28
PT808312E (pt)	2001-03-30
US20030105139A1 (en)	2003-06-05
AP9701036A0 (en)	1997-07-31
ATE197300T1 (de)	2000-11-15
HK1003883A1 (en)	1998-11-13
DE69610822T2 (de)	2001-06-07
RO115522B1 (ro)	2000-03-30
CZ294097B6 (cs)	2004-10-13
JPH10513442A (ja)	1998-12-22
EP0808312B1 (de)	2000-11-02
EA000304B1 (ru)	1999-04-29
PL184490B1 (pl)	2002-11-29
NO973543D0 (no)	1997-08-01
CN1151147C (zh)	2004-05-26
DE69610822D1 (de)	2000-12-07
FI973205A0 (fi)	1997-08-01
NO973543L (no)	1997-10-01
FI973205A7 (fi)	1997-10-01

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