HRP20050457A2 - Aminoalkoxyindoles as 5-ht6-receptor ligands for the treatment of cns-disorders - Google Patents

Aminoalkoxyindoles as 5-ht6-receptor ligands for the treatment of cns-disorders Download PDF

Info

Publication number: HRP20050457A2
Authority: HR; Croatia
Prior art keywords: benzenesulfonyl; indole; compound; pyrrolidin; ethoxy
Prior art date: 2002-12-03

Application number

HR20050457A

Other languages

English (en)

Croatian (hr)

Inventor

Zhao Shu-Hai

Original Assignee

F. Hoffmann - La Roche Ag

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.)

2002-12-03

Filing date

2005-05-24

Publication date

2005-10-31

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=32469485&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20050457(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2005-05-24 Application filed by F. Hoffmann - La Roche Ag filed Critical F. Hoffmann - La Roche Ag

2005-10-31 Publication of HRP20050457A2 publication Critical patent/HRP20050457A2/hr

Links

238000011282 treatment Methods 0.000 title claims description 17
239000003446 ligand Substances 0.000 title description 7
108091005435 5-HT6 receptors Proteins 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims description 138
-1 2,3-dichlorophenyl Chemical group 0.000 claims description 129
125000000217 alkyl group Chemical group 0.000 claims description 54
229910052739 hydrogen Inorganic materials 0.000 claims description 53
239000001257 hydrogen Substances 0.000 claims description 53
238000000034 method Methods 0.000 claims description 50
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 27
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
201000010099 disease Diseases 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 23
125000005843 halogen group Chemical group 0.000 claims description 23
125000001188 haloalkyl group Chemical group 0.000 claims description 22
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 21
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 15
125000004429 atom Chemical group 0.000 claims description 15
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150000002475 indoles Chemical class 0.000 claims description 15
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239000000651 prodrug Substances 0.000 claims description 9
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125000002947 alkylene group Chemical group 0.000 claims description 8
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125000004404 heteroalkyl group Chemical group 0.000 claims description 7
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239000003937 drug carrier Substances 0.000 claims description 6
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
125000003107 substituted aryl group Chemical group 0.000 claims description 6
RMPRCOIPSPOSEN-UHFFFAOYSA-N 2-[[3-(2-fluorophenyl)sulfonyl-1h-indol-7-yl]oxy]ethanamine Chemical compound C=1NC=2C(OCCN)=CC=CC=2C=1S(=O)(=O)C1=CC=CC=C1F RMPRCOIPSPOSEN-UHFFFAOYSA-N 0.000 claims description 5
LZDOWFDYOXQTLX-UHFFFAOYSA-N 3-phenylsulfanyl-7-(2-pyrrolidin-1-ylethoxy)-1h-indole Chemical compound C=1C=CC=2C(SC=3C=CC=CC=3)=CNC=2C=1OCCN1CCCC1 LZDOWFDYOXQTLX-UHFFFAOYSA-N 0.000 claims description 5
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YLSVTTRGFBYGJR-UHFFFAOYSA-N 2-[[2-(benzenesulfonyl)-1h-indol-7-yl]oxy]-n-methylethanamine Chemical compound N1C=2C(OCCNC)=CC=CC=2C=C1S(=O)(=O)C1=CC=CC=C1 YLSVTTRGFBYGJR-UHFFFAOYSA-N 0.000 claims description 3
BLGMYEPZKMVQMA-UHFFFAOYSA-N 2-[[3-(2-fluorophenyl)sulfonyl-1h-indol-7-yl]oxy]-n,n-dimethylethanamine Chemical compound C=1NC=2C(OCCN(C)C)=CC=CC=2C=1S(=O)(=O)C1=CC=CC=C1F BLGMYEPZKMVQMA-UHFFFAOYSA-N 0.000 claims description 3
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CNNBHYHJRQTELP-UHFFFAOYSA-N 4-(azetidin-3-ylmethoxy)-2-(benzenesulfonyl)-1h-indole Chemical compound C=1C=CC=CC=1S(=O)(=O)C(NC1=CC=C2)=CC1=C2OCC1CNC1 CNNBHYHJRQTELP-UHFFFAOYSA-N 0.000 claims description 3
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125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
DTONEWKRXMSKEM-UHFFFAOYSA-N 2-[[2-(benzenesulfonyl)-1h-indol-4-yl]oxy]-n-methylethanamine Chemical compound C=1C=2C(OCCNC)=CC=CC=2NC=1S(=O)(=O)C1=CC=CC=C1 DTONEWKRXMSKEM-UHFFFAOYSA-N 0.000 claims description 2
HKSMTOWIEYROOE-UHFFFAOYSA-N 2-[[3-(2-fluorophenyl)sulfonyl-1h-indol-7-yl]oxy]-n-methylethanamine Chemical compound C=1NC=2C(OCCNC)=CC=CC=2C=1S(=O)(=O)C1=CC=CC=C1F HKSMTOWIEYROOE-UHFFFAOYSA-N 0.000 claims description 2
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ZSJPTBOKDUFREA-UHFFFAOYSA-N 2-[[3-(benzenesulfonyl)-1h-indol-7-yl]oxy]-n,n-dimethylethanamine Chemical compound C=1NC=2C(OCCN(C)C)=CC=CC=2C=1S(=O)(=O)C1=CC=CC=C1 ZSJPTBOKDUFREA-UHFFFAOYSA-N 0.000 claims description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
AFDLZYKPCWEPTE-UHFFFAOYSA-N 3-(2,3-dichlorophenyl)sulfonyl-7-(2-pyrrolidin-1-ylethoxy)-1h-indole Chemical compound ClC1=CC=CC(S(=O)(=O)C=2C3=CC=CC(OCCN4CCCC4)=C3NC=2)=C1Cl AFDLZYKPCWEPTE-UHFFFAOYSA-N 0.000 claims description 2
UKUUMYLIKIQMSU-UHFFFAOYSA-N 3-(2-chlorophenyl)sulfonyl-7-(2-pyrrolidin-1-ylethoxy)-1h-indole Chemical compound ClC1=CC=CC=C1S(=O)(=O)C(C1=CC=C2)=CNC1=C2OCCN1CCCC1 UKUUMYLIKIQMSU-UHFFFAOYSA-N 0.000 claims description 2
IPGRBAKTDOCPAA-UHFFFAOYSA-N 3-(2-fluorophenyl)sulfonyl-7-(2-pyrrolidin-1-ylethoxy)-1h-indole Chemical compound FC1=CC=CC=C1S(=O)(=O)C(C1=CC=C2)=CNC1=C2OCCN1CCCC1 IPGRBAKTDOCPAA-UHFFFAOYSA-N 0.000 claims description 2
ZKNXCMRWUONPEN-ZDUSSCGKSA-N 3-(2-fluorophenyl)sulfonyl-7-[[(2s)-pyrrolidin-2-yl]methoxy]-1h-indole Chemical compound FC1=CC=CC=C1S(=O)(=O)C(C1=CC=C2)=CNC1=C2OC[C@H]1NCCC1 ZKNXCMRWUONPEN-ZDUSSCGKSA-N 0.000 claims description 2
VKVFAFYHUVUDIU-UHFFFAOYSA-N 3-(2-methoxyphenyl)sulfonyl-7-(2-pyrrolidin-1-ylethoxy)-1h-indole Chemical compound COC1=CC=CC=C1S(=O)(=O)C(C1=CC=C2)=CNC1=C2OCCN1CCCC1 VKVFAFYHUVUDIU-UHFFFAOYSA-N 0.000 claims description 2
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RSANRYVVMXGIMG-UHFFFAOYSA-N 3-(3-methoxyphenyl)sulfonyl-7-(2-pyrrolidin-1-ylethoxy)-1h-indole Chemical compound COC1=CC=CC(S(=O)(=O)C=2C3=CC=CC(OCCN4CCCC4)=C3NC=2)=C1 RSANRYVVMXGIMG-UHFFFAOYSA-N 0.000 claims description 2
ITLOEBYATZEINN-UHFFFAOYSA-N 3-(4-chlorophenyl)sulfonyl-7-(2-pyrrolidin-1-ylethoxy)-1h-indole Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(C1=CC=C2)=CNC1=C2OCCN1CCCC1 ITLOEBYATZEINN-UHFFFAOYSA-N 0.000 claims description 2
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VDXUQGNABCWOEH-UHFFFAOYSA-N tert-butyl n-[2-[[3-(benzenesulfonyl)-1h-indol-7-yl]oxy]ethyl]-n-methylcarbamate Chemical compound C=1NC=2C(OCCN(C)C(=O)OC(C)(C)C)=CC=CC=2C=1S(=O)(=O)C1=CC=CC=C1 VDXUQGNABCWOEH-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
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125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
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125000000335 thiazolyl group Chemical group 0.000 description 1
230000008719 thickening Effects 0.000 description 1
125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

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- A61K31/4025—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 not condensed and containing further heterocyclic rings, e.g. cromakalim
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
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Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
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Addiction (AREA)
Psychiatry (AREA)
Epidemiology (AREA)
Pain & Pain Management (AREA)
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Diabetes (AREA)
Hospice & Palliative Care (AREA)
Obesity (AREA)
Hematology (AREA)
Nutrition Science (AREA)
Child & Adolescent Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Steroid Compounds (AREA)

HR20050457A 2002-12-03 2005-05-24 Aminoalkoxyindoles as 5-ht6-receptor ligands for the treatment of cns-disorders HRP20050457A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US43050602P	2002-12-03	2002-12-03
PCT/EP2003/013372 WO2004050085A1 (en)	2002-12-03	2003-11-27	Aminoalkoxyindoles as 5-ht6-receptor ligands for the treatment of cns-disorders

Publications (1)

Publication Number	Publication Date
HRP20050457A2 true HRP20050457A2 (en)	2005-10-31

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ID=32469485

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20050457A HRP20050457A2 (en)	2002-12-03	2005-05-24	Aminoalkoxyindoles as 5-ht6-receptor ligands for the treatment of cns-disorders

Country Status (24)

Country	Link
US (1)	US7084169B2 (zh)
EP (1)	EP1569638B1 (zh)
JP (1)	JP4339795B2 (zh)
KR (1)	KR100755580B1 (zh)
CN (1)	CN1713908B (zh)
AR (1)	AR042155A1 (zh)
AT (1)	ATE372113T1 (zh)
AU (1)	AU2003289903B2 (zh)
BR (1)	BR0316962A (zh)
CA (1)	CA2508315A1 (zh)
DE (1)	DE60316180T2 (zh)
ES (1)	ES2291722T3 (zh)
HR (1)	HRP20050457A2 (zh)
MX (1)	MXPA05005790A (zh)
MY (1)	MY138466A (zh)
NO (1)	NO20052730L (zh)
NZ (1)	NZ539950A (zh)
PA (1)	PA8589801A1 (zh)
PE (1)	PE20040763A1 (zh)
PL (1)	PL377464A1 (zh)
RU (1)	RU2350602C2 (zh)
TW (1)	TWI284124B (zh)
WO (1)	WO2004050085A1 (zh)
ZA (1)	ZA200504412B (zh)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5417142A (en) *	1992-12-18	1995-05-23	Caterpillar Inc.	Hydraulic amplifier
BRPI0308696B8 (pt)	2002-03-27	2021-05-25	Axovant Sciences Gmbh	composto derivado de quinolina, seu processo de preparação, sua composição farmacêutica e seus usos
WO2005012254A1 (en)	2003-07-22	2005-02-10	Arena Pharmaceuticals, Inc.	Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related therto
GB0500604D0 (en) *	2005-01-13	2005-02-16	Astrazeneca Ab	Novel process
US20090221644A1 (en) *	2005-06-30	2009-09-03	Stuart Edward Bradley	Gpcr Agonists
CA2619010C (en) *	2005-08-15	2013-10-01	Wyeth	Substituted-3-sulfonylindazole derivatives as 5-hydroxytryptamine-6 ligands
CN101370775A (zh) *	2006-01-13	2009-02-18	惠氏公司	作为5-羟基色胺受体配体的经磺酰基取代1h-吲哚
MX2008013053A (es) *	2006-04-12	2008-10-17	Wyeth Corp	Derivados de dihidri[1,4]oxazino[2,3,4-hi]indazol-sustituidos como ligandos de 5-hidroxitriptamina-6.
US20100041672A1 (en) *	2007-03-21	2010-02-18	Glaxo Group Limited	Use of quinoline derivatives in the treatment of pain and irritable bowel syndrome
EP2508177A1 (en)	2007-12-12	2012-10-10	Glaxo Group Limited	Combinations comprising 3-phenylsulfonyl-8-piperazinyl-1yl-quinoline
WO2009123714A2 (en)	2008-04-02	2009-10-08	Arena Pharmaceuticals, Inc.	Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor
US9126946B2 (en)	2008-10-28	2015-09-08	Arena Pharmaceuticals, Inc.	Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea and crystalline forms related thereto
CN102558020B (zh) *	2011-12-12	2013-09-18	温州大学	一种3-芳巯基吲哚类化合物的合成方法
CN103288707B (zh) *	2013-05-28	2015-12-23	浙江大学	一种3-苯巯基吲哚衍生物的制备方法
AU2015286049B2 (en)	2014-07-08	2018-03-01	Sunshine Lake Pharma Co., Ltd.	Aromatic heterocyclic derivatives and pharmaceutical applications thereof
MX2017016413A (es)	2015-06-12	2018-08-01	Axovant Sciences Gmbh	Derivados de diaril y arilheteroaril urea como moduladores del receptor 5ht2a de serotonina útiles para la profilaxis y el tratamineto de un trastorno conductual del sueño rem.
MX2018000465A (es)	2015-07-15	2018-09-17	Axovant Sciences Gmbh	Derivados de diaril y arilheteroaril urea como moduladores del receptor de serotonina 5-ht2a útiles para la profilaxis y el tratamiento de alucinaciones asociadas con una enfermedad neurodegenerativa.

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1139760A (en)	1979-03-07	1983-01-18	Makiko Sakai	1,4-dioxaspiro¬4,5\| decene compounds
FR2589863B1 (fr)	1985-11-12	1988-07-29	Sanofi Sa	Derives d'hydroxy-4 indole, leur procede de preparation et leur utilisation
US5254595A (en)	1988-12-23	1993-10-19	Elf Sanofi	Aryloxypropanolaminotetralins, a process for their preparation and pharmaceutical compositions containing them
US4939138A (en) *	1988-12-29	1990-07-03	Sterling Drug Inc.	2- and 3-aminomethyl-6-arylcarbonyl-2,3-dihydropyrrolo(1,2,3-DE)-1,4-benzoxazines
FR2740686B1 (fr)	1995-11-03	1998-01-16	Sanofi Sa	Formulation pharmaceutique lyophilisee stable
PT923548E (pt) *	1996-08-27	2003-06-30	Wyeth Corp	4-aminoetoxi-indolos como agonistas d2 da dopaminae como ligandos da 5ht1a
GB9902452D0 (en)	1999-02-05	1999-03-24	Zeneca Ltd	Chemical compounds
FR2791344B1 (fr)	1999-03-25	2002-02-15	Adir	Nouveaux derives dimeriques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR2793793B1 (fr)	1999-05-19	2004-02-27	Adir	Nouveaux derives dimeriques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
TWI222450B (en) *	1999-07-28	2004-10-21	Upjohn Co	Oxazinocarbazoles for the treatment of CNS diseases
TW593278B (en)	2001-01-23	2004-06-21	Wyeth Corp	1-aryl-or 1-alkylsulfonylbenzazole derivatives as 5-hydroxytryptamine-6 ligands
MXPA03009490A (es) *	2001-04-20	2004-02-12	Wyeth Corp	Derivados de heterociclilalcoxi-,-alquiltio-y- alquilaminobenzazol como ligando de 5-hidroxitriptamina-6.

2003
- 2003-11-27 TW TW092133339A patent/TWI284124B/zh not_active IP Right Cessation
- 2003-11-27 CA CA002508315A patent/CA2508315A1/en not_active Abandoned
- 2003-11-27 AU AU2003289903A patent/AU2003289903B2/en not_active Ceased
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- 2003-11-27 EP EP03782240A patent/EP1569638B1/en not_active Expired - Lifetime
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- 2003-11-27 ES ES03782240T patent/ES2291722T3/es not_active Expired - Lifetime
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- 2003-11-27 BR BR0316962-6A patent/BR0316962A/pt not_active IP Right Cessation
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- 2003-11-27 DE DE60316180T patent/DE60316180T2/de not_active Expired - Lifetime
- 2003-11-27 NZ NZ539950A patent/NZ539950A/en unknown
- 2003-11-27 AT AT03782240T patent/ATE372113T1/de not_active IP Right Cessation
- 2003-11-27 MX MXPA05005790A patent/MXPA05005790A/es active IP Right Grant
- 2003-11-27 RU RU2005121125/04A patent/RU2350602C2/ru not_active IP Right Cessation
- 2003-11-28 PA PA20038589801A patent/PA8589801A1/es unknown
- 2003-11-28 PE PE2003001211A patent/PE20040763A1/es not_active Application Discontinuation
- 2003-12-01 AR ARP030104414A patent/AR042155A1/es unknown
- 2003-12-01 US US10/724,683 patent/US7084169B2/en not_active Expired - Fee Related
- 2003-12-02 MY MYPI20034589A patent/MY138466A/en unknown
2005
- 2005-05-24 HR HR20050457A patent/HRP20050457A2/hr not_active Application Discontinuation
- 2005-05-30 ZA ZA200504412A patent/ZA200504412B/en unknown
- 2005-06-07 NO NO20052730A patent/NO20052730L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
JP2006509777A (ja)	2006-03-23
MXPA05005790A (es)	2005-10-18
TWI284124B (en)	2007-07-21
BR0316962A (pt)	2005-10-25
EP1569638B1 (en)	2007-09-05
AR042155A1 (es)	2005-06-08
NZ539950A (en)	2007-05-31
RU2005121125A (ru)	2006-02-20
CN1713908B (zh)	2010-05-12
ATE372113T1 (de)	2007-09-15
NO20052730D0 (no)	2005-06-07
CN1713908A (zh)	2005-12-28
EP1569638A1 (en)	2005-09-07
RU2350602C2 (ru)	2009-03-27
CA2508315A1 (en)	2004-06-17
US7084169B2 (en)	2006-08-01
AU2003289903A1 (en)	2004-06-23
NO20052730L (no)	2005-08-23
KR20050084155A (ko)	2005-08-26
US20040132799A1 (en)	2004-07-08
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US8318770B2 (en)	2012-11-27	Tetrahydroquinoline indole derivatives and uses thereof
AU2002345587A1 (en)	2003-01-02	4-Piperazinylindole derivatives with 5-HT6 receptor affinity