CN102439005A - 作为γ-分泌酶调节剂的新的取代的吲唑和氮杂-吲唑衍生物 - Google Patents
作为γ-分泌酶调节剂的新的取代的吲唑和氮杂-吲唑衍生物 Download PDFInfo
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- CN102439005A CN102439005A CN2010800201316A CN201080020131A CN102439005A CN 102439005 A CN102439005 A CN 102439005A CN 2010800201316 A CN2010800201316 A CN 2010800201316A CN 201080020131 A CN201080020131 A CN 201080020131A CN 102439005 A CN102439005 A CN 102439005A
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- phenyl
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- 229940124648 γ-Secretase Modulator Drugs 0.000 title abstract description 9
- VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 title abstract description 8
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical class C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 title abstract 2
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- 238000011282 treatment Methods 0.000 claims description 32
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
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- 235000019439 ethyl acetate Nutrition 0.000 description 13
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 12
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 11
- 229910052796 boron Inorganic materials 0.000 description 11
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
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Classifications
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- 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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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
- C07D403/14—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 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
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
Landscapes
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
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- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
Claims (10)
Applications Claiming Priority (3)
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EP09159615 | 2009-05-07 | ||
EP09159615.5 | 2009-05-07 | ||
PCT/EP2010/056074 WO2010145883A1 (en) | 2009-05-07 | 2010-05-05 | Novel substituted indazole and aza-indazole derivatives as gamma secretase modulators |
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CN102439005B CN102439005B (zh) | 2015-07-22 |
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EP (1) | EP2427453B1 (zh) |
JP (1) | JP5559309B2 (zh) |
KR (1) | KR20120024555A (zh) |
CN (1) | CN102439005B (zh) |
AR (1) | AR076850A1 (zh) |
AU (1) | AU2010262036B2 (zh) |
BR (1) | BRPI1011190A8 (zh) |
CA (1) | CA2755467A1 (zh) |
EA (1) | EA019702B1 (zh) |
ES (1) | ES2431619T3 (zh) |
IL (1) | IL216113A (zh) |
MX (1) | MX2011011753A (zh) |
MY (1) | MY152998A (zh) |
NZ (1) | NZ596843A (zh) |
SG (1) | SG175317A1 (zh) |
TW (1) | TWI461419B (zh) |
UA (1) | UA105377C2 (zh) |
WO (1) | WO2010145883A1 (zh) |
ZA (1) | ZA201108117B (zh) |
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CN103880683A (zh) * | 2014-02-26 | 2014-06-25 | 南通大学 | 一种3-溴-2-硝基苯甲醛的化学合成方法 |
CN105585547A (zh) * | 2016-03-09 | 2016-05-18 | 中国科学院广州生物医药与健康研究院 | 一种4-五氟化硫苯酚类化合物及制备方法以及五氟化硫取代苯并吡喃类化合物的制备方法 |
CN107922437A (zh) * | 2015-09-09 | 2018-04-17 | 豪夫迈·罗氏有限公司 | 桥连哌啶衍生物 |
CN114195702A (zh) * | 2020-09-18 | 2022-03-18 | 瑞博(杭州)医药科技有限公司 | 一种用于合成抗肿瘤药物尼拉帕利的中间体及其制备方法 |
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PA8854101A1 (es) | 2008-12-18 | 2010-07-27 | Ortho Mcneil Janssen Pharm | Derivados de imidazol bicíclicos sustituidos como moduladores de gamma secretasa |
MX2011008335A (es) | 2009-02-06 | 2011-09-06 | Ortho Mcneil Janssen Pharm | Novedosos compuestos heterociclicos biciclicos sustituidos como moduladores de la gamma secretasa. |
TWI461425B (zh) | 2009-02-19 | 2014-11-21 | Janssen Pharmaceuticals Inc | 作為伽瑪分泌酶調節劑之新穎經取代的苯并唑、苯并咪唑、唑并吡啶及咪唑并吡啶衍生物類 |
JP5559309B2 (ja) | 2009-05-07 | 2014-07-23 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | γ分泌酵素調節物質としての新規置換インダゾールおよびアザインダゾール誘導体 |
SG177644A1 (en) | 2009-07-15 | 2012-03-29 | Janssen Pharmaceuticals Inc | Substituted triazole and imidazole derivatives as gamma secretase modulators |
US9079886B2 (en) | 2010-01-15 | 2015-07-14 | Janssen Pharmaceuticals, Inc. | Substituted triazole derivatives as gamma secretase modulators |
US8987276B2 (en) | 2011-03-24 | 2015-03-24 | Janssen Pharmaceuticals, Inc. | Substituted triazolyl piperazine and triazolyl piperidine derivatives as gamma secretase modulators |
TWI567079B (zh) | 2011-07-15 | 2017-01-21 | 健生醫藥公司 | 作為伽瑪分泌酶調節劑之新穎的經取代的吲哚衍生物 |
BR112014028395B1 (pt) | 2012-05-16 | 2022-02-01 | Janssen Pharmaceuticals, Inc. | Derivados 3,4-di-hidro-2h-pirido[1,2-a]pirazina-1,6-diona substituídos úteis para o tratamento de (inter alia) doença de alzheimer e composição farmacêutica que os compreende |
CN104918938B (zh) | 2012-12-20 | 2017-08-15 | 詹森药业有限公司 | 新颖的作为γ分泌酶调节剂的三环3,4‑二氢‑2H‑吡啶并[1,2‑a]吡嗪‑1,6‑二酮衍生物 |
WO2014111457A1 (en) | 2013-01-17 | 2014-07-24 | Janssen Pharmaceutica Nv | Novel substituted pyrido-piperazinone derivatives as gamma secretase modulators |
WO2014127816A1 (en) * | 2013-02-21 | 2014-08-28 | Boehringer Ingelheim International Gmbh | Dihydropteridinones ii |
US10562897B2 (en) | 2014-01-16 | 2020-02-18 | Janssen Pharmaceutica Nv | Substituted 3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-diones as gamma secretase modulators |
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CN103880683A (zh) * | 2014-02-26 | 2014-06-25 | 南通大学 | 一种3-溴-2-硝基苯甲醛的化学合成方法 |
CN103880683B (zh) * | 2014-02-26 | 2018-06-22 | 南通大学 | 一种3-溴-2-硝基苯甲醛的化学合成方法 |
CN107922437A (zh) * | 2015-09-09 | 2018-04-17 | 豪夫迈·罗氏有限公司 | 桥连哌啶衍生物 |
CN105585547A (zh) * | 2016-03-09 | 2016-05-18 | 中国科学院广州生物医药与健康研究院 | 一种4-五氟化硫苯酚类化合物及制备方法以及五氟化硫取代苯并吡喃类化合物的制备方法 |
CN114195702A (zh) * | 2020-09-18 | 2022-03-18 | 瑞博(杭州)医药科技有限公司 | 一种用于合成抗肿瘤药物尼拉帕利的中间体及其制备方法 |
Also Published As
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JP5559309B2 (ja) | 2014-07-23 |
TW201105658A (en) | 2011-02-16 |
US20120095036A1 (en) | 2012-04-19 |
EP2427453A1 (en) | 2012-03-14 |
CA2755467A1 (en) | 2010-12-23 |
MX2011011753A (es) | 2011-11-29 |
TWI461419B (zh) | 2014-11-21 |
US8835482B2 (en) | 2014-09-16 |
ZA201108117B (en) | 2015-06-24 |
CN102439005B (zh) | 2015-07-22 |
KR20120024555A (ko) | 2012-03-14 |
SG175317A1 (en) | 2011-11-28 |
EA201171363A1 (ru) | 2012-04-30 |
JP2012526078A (ja) | 2012-10-25 |
IL216113A0 (en) | 2012-01-31 |
AU2010262036B2 (en) | 2014-10-30 |
EP2427453B1 (en) | 2013-07-17 |
UA105377C2 (uk) | 2014-05-12 |
IL216113A (en) | 2015-02-26 |
NZ596843A (en) | 2012-12-21 |
AU2010262036A1 (en) | 2011-09-22 |
BRPI1011190A8 (pt) | 2016-11-16 |
EA019702B1 (ru) | 2014-05-30 |
AR076850A1 (es) | 2011-07-13 |
BRPI1011190A2 (pt) | 2016-03-15 |
MY152998A (en) | 2014-12-31 |
ES2431619T3 (es) | 2013-11-27 |
WO2010145883A1 (en) | 2010-12-23 |
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