CN101687802A - 适于治疗对多巴胺d3受体调节有反应的病症的苯磺酰胺化合物 - Google Patents
适于治疗对多巴胺d3受体调节有反应的病症的苯磺酰胺化合物 Download PDFInfo
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- CN101687802A CN101687802A CN200880023090A CN200880023090A CN101687802A CN 101687802 A CN101687802 A CN 101687802A CN 200880023090 A CN200880023090 A CN 200880023090A CN 200880023090 A CN200880023090 A CN 200880023090A CN 101687802 A CN101687802 A CN 101687802A
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- methyl
- compound
- fluoro
- piperazine
- benzsulfamide
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
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Landscapes
- Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- General Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Medicinal Chemistry (AREA)
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- Pregnancy & Childbirth (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
实施例 | Ki(D3)[nM] | 相对于D2L*的选择性 |
1 | +++ | >50 |
2 | +++ | >50 |
5 | +++ | >50 |
6 | +++ | >50 |
比较实施例7 | + | >10 |
8 | +++ | >50 |
9 | +++ | >50 |
10 | +++ | >50 |
11 | +++ | >50 |
12 | +++ | >50 |
13 | +++ | >50 |
14 | +++ | >50 |
15 | +++ | >50 |
16 | +++ | >50 |
17 | +++ | >50 |
18 | +++ | >50 |
Claims (28)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07119788.3 | 2007-10-31 | ||
EP07119788 | 2007-10-31 | ||
PCT/EP2008/064732 WO2009056600A1 (en) | 2007-10-31 | 2008-10-30 | Benzenesulfonamide compounds suitable for treating disorders that respond to modulation of the dopamine d3 receptor |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101687802A true CN101687802A (zh) | 2010-03-31 |
CN101687802B CN101687802B (zh) | 2014-02-26 |
Family
ID=40280677
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN200880023090.9A Expired - Fee Related CN101687802B (zh) | 2007-10-31 | 2008-10-30 | 适于治疗对多巴胺d3受体调节有反应的病症的苯磺酰胺化合物 |
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US (4) | US20100210664A1 (zh) |
EP (1) | EP2203426B9 (zh) |
JP (1) | JP5680416B2 (zh) |
KR (1) | KR20100080500A (zh) |
CN (1) | CN101687802B (zh) |
AT (1) | ATE522505T1 (zh) |
AU (1) | AU2008320875B2 (zh) |
BR (1) | BRPI0812978A2 (zh) |
CA (1) | CA2690976A1 (zh) |
CO (1) | CO6251289A2 (zh) |
CR (1) | CR11188A (zh) |
DO (1) | DOP2009000295A (zh) |
EC (1) | ECSP099832A (zh) |
ES (1) | ES2371308T3 (zh) |
GT (1) | GT200900332A (zh) |
IL (1) | IL202814A (zh) |
MX (1) | MX2009014236A (zh) |
MY (1) | MY153300A (zh) |
NZ (1) | NZ582095A (zh) |
RU (1) | RU2485103C2 (zh) |
TW (1) | TWI469782B (zh) |
UA (1) | UA99628C2 (zh) |
WO (1) | WO2009056600A1 (zh) |
ZA (1) | ZA200909171B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR101781723B1 (ko) | 2013-06-27 | 2017-10-23 | 화이자 인코포레이티드 | 헤테로방향족 화합물, 및 도파민 d1 리간드로서 이의 용도 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1805937A (zh) * | 2003-04-14 | 2006-07-19 | 阿伯特有限及两合公司 | 具有多巴胺d3受体亲和性的n-[ (哌嗪基)杂芳基]芳基磺酰胺化合物 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
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SE0102439D0 (sv) * | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
US7320979B2 (en) * | 2003-04-14 | 2008-01-22 | Abbott Gmbh & Co. Kg. | N-[(piperazinyl)hetaryl]arylsulfonamide compounds |
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2008
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CN1805937A (zh) * | 2003-04-14 | 2006-07-19 | 阿伯特有限及两合公司 | 具有多巴胺d3受体亲和性的n-[ (哌嗪基)杂芳基]芳基磺酰胺化合物 |
Non-Patent Citations (2)
Title |
---|
STEVEN M. BROMIDGE, ET AL.: "5-Chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046): A Potent, Selective, and Orally Bioavailable 5-HT6 Receptor Antagonist", 《J. MED. CHEM.》 * |
STEVEN M. BROMIDGE, ET AL.: "Novel (4-Piperazin-1-ylquinolin-6-yl) Arylsulfonamides with High Affinity and Selectivity for the 5-HT6 Receptor", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
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