DE60017446T2 - Isochinolin- und Chinazolinderivate mit kombinierter 5-HT1A-, 5-HT1B- und 5-HT1D- Rezeptoraffinität - Google Patents
Isochinolin- und Chinazolinderivate mit kombinierter 5-HT1A-, 5-HT1B- und 5-HT1D- Rezeptoraffinität Download PDFInfo
- Publication number
- DE60017446T2 DE60017446T2 DE60017446T DE60017446T DE60017446T2 DE 60017446 T2 DE60017446 T2 DE 60017446T2 DE 60017446 T DE60017446 T DE 60017446T DE 60017446 T DE60017446 T DE 60017446T DE 60017446 T2 DE60017446 T2 DE 60017446T2
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- Germany
- Prior art keywords
- formula
- isoquinoline
- radical
- mmol
- dihydro
- Prior art date
- 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
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- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 title abstract description 11
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract 2
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 title 1
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 title 1
- 101710138639 5-hydroxytryptamine receptor 1B Proteins 0.000 title 1
- 102100027499 5-hydroxytryptamine receptor 1B Human genes 0.000 title 1
- 101710138068 5-hydroxytryptamine receptor 1D Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 43
- 238000011282 treatment Methods 0.000 claims abstract description 22
- 230000008569 process Effects 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 93
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- 150000003839 salts Chemical class 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
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- 208000035475 disorder Diseases 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 239000003446 ligand Substances 0.000 claims description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 5
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- 150000002367 halogens Chemical class 0.000 claims description 5
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- TXRGJNXLUOJBIV-UHFFFAOYSA-N (5-methyl-1-phenylpyrazol-4-yl)-[8-(4-methylpiperazin-1-yl)-2,3-dihydropyrrolo[3,2-g]isoquinolin-1-yl]methanone Chemical compound C1CN(C)CCN1C(C1=C2)=NC=CC1=CC1=C2N(C(=O)C2=C(N(N=C2)C=2C=CC=CC=2)C)CC1 TXRGJNXLUOJBIV-UHFFFAOYSA-N 0.000 claims description 4
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 2
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- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 235000019439 ethyl acetate Nutrition 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
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- BMFJTABNNAHEMU-UHFFFAOYSA-N (1-benzyl-2,3-dihydropyrrolo[3,2-g]isoquinolin-8-yl) trifluoromethanesulfonate Chemical compound C1=2C=C3C(OS(=O)(=O)C(F)(F)F)=NC=CC3=CC=2CCN1CC1=CC=CC=C1 BMFJTABNNAHEMU-UHFFFAOYSA-N 0.000 description 5
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- ILHDYUNGKWCIMT-UHFFFAOYSA-N 1-[4-(2,3-dihydro-1h-pyrrolo[3,2-g]isoquinolin-8-yl)piperazin-1-yl]-2,2,2-trifluoroethanone Chemical compound C1CN(C(=O)C(F)(F)F)CCN1C(C1=C2)=NC=CC1=CC1=C2NCC1 ILHDYUNGKWCIMT-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—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
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61P25/24—Antidepressants
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (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)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9926304 | 1999-11-05 | ||
| GBGB9926304.8A GB9926304D0 (en) | 1999-11-05 | 1999-11-05 | Novel compounds |
| GB0017880A GB0017880D0 (en) | 2000-07-20 | 2000-07-20 | Novel compounds |
| GB0017880 | 2000-07-20 | ||
| PCT/EP2000/010908 WO2001032626A1 (en) | 1999-11-05 | 2000-11-02 | Isoquinoline and quinazoline derivatives having a combined 5ht1a, 5ht1b and 5ht1d receptor activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60017446D1 DE60017446D1 (de) | 2005-02-17 |
| DE60017446T2 true DE60017446T2 (de) | 2006-03-02 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60017446T Expired - Fee Related DE60017446T2 (de) | 1999-11-05 | 2000-11-02 | Isochinolin- und Chinazolinderivate mit kombinierter 5-HT1A-, 5-HT1B- und 5-HT1D- Rezeptoraffinität |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20050239797A1 (enExample) |
| EP (1) | EP1228043B1 (enExample) |
| JP (1) | JP2003513075A (enExample) |
| AT (1) | ATE286883T1 (enExample) |
| AU (1) | AU1028601A (enExample) |
| DE (1) | DE60017446T2 (enExample) |
| ES (1) | ES2234683T3 (enExample) |
| PE (1) | PE20010956A1 (enExample) |
| UY (1) | UY26426A1 (enExample) |
| WO (1) | WO2001032626A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7229986B2 (en) | 2000-05-16 | 2007-06-12 | Takeda Pharmaceutical Company Ltd. | Melanin-concentrating hormone antagonist |
| DE10315569A1 (de) | 2003-04-05 | 2004-10-14 | Merck Patent Gmbh | Substituierte Pyrazolverbindungen |
| DE10315571A1 (de) * | 2003-04-05 | 2004-10-14 | Merck Patent Gmbh | Pyrazolverbindungen |
| DE10315573A1 (de) | 2003-04-05 | 2004-10-14 | Merck Patent Gmbh | Substituierte Pyrazole |
| GB0316915D0 (en) | 2003-07-18 | 2003-08-20 | Glaxo Group Ltd | Compounds |
| BRPI0412259B1 (pt) | 2003-07-22 | 2019-08-20 | Astex Therapeutics Limited | Compostos de 1H-pirazol 3,4-dissubstituídos como moduladores de quinases dependentes de ciclina (CDK), seus usos, processo para a preparação dos mesmos e composição farmacêutica |
| RU2006129464A (ru) * | 2004-01-16 | 2008-02-27 | Ф.Хоффманн-Ля Рош Аг (Ch) | Производные 1-бензил-5-пиперазин-1-ил-3, 4-дигидро-1н-хиназолин-2-она и соответствующие производные 1н-бензо (1, 2, 6) тиадиазин-2, 2-диоксида и 1, 4-дигидробензо (1, 3)оксазин-2-она в качестве модуляторов рецептора 5-гидрокситриптамина (5нт) для лечения заболевания центральной нервной системы |
| US9066903B2 (en) * | 2006-02-28 | 2015-06-30 | The United States Of America As Represented By The Department Of Veterans Affairs | Pharmacological treatment of Parkinson's disease |
| US20090099175A1 (en) * | 2006-03-01 | 2009-04-16 | Arrington Mark P | Phosphodiesterase 10 inhibitors |
| WO2008115593A1 (en) | 2007-03-21 | 2008-09-25 | The University Of Montana | 1-[(2'-substituted)-piperazin-1'-yl]-isoquinolines as norepinephrine transporter inhibitor therapeutics and positron emission tomography imaging agents |
| US8987473B2 (en) | 2011-01-28 | 2015-03-24 | Sato Pharmaceutical Co., Ltd. | Ring-fused compound |
| US10092574B2 (en) | 2012-09-26 | 2018-10-09 | Valorisation-Recherche, Limited Partnership | Inhibitors of polynucleotide repeat-associated RNA foci and uses thereof |
| KR101709127B1 (ko) * | 2015-06-16 | 2017-02-22 | 경동제약 주식회사 | Dpp-iv 억제제의 제조를 위한 신규 중간체, 이의 제조방법 및 이를 이용한 dpp-iv 억제제의 제조방법 |
| CN112480007B (zh) * | 2020-12-08 | 2022-11-18 | 宿迁市科莱博生物化学有限公司 | 一种1，3-二甲基-1h-吡唑-4-羧酸的合成方法 |
| WO2025190395A2 (en) * | 2024-03-14 | 2025-09-18 | Pharmaengine, Inc. | Mta-cooperative prmt5 inhibitor |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3778440A (en) * | 1970-12-07 | 1973-12-11 | Sandoz Ag | 1-substituted amino-isoquinolines and nitrates thereof |
| US3932412A (en) * | 1970-12-07 | 1976-01-13 | Sandoz, Inc. | 1-(4-Hydroxyalkylpiperazino)-isoquinoline nitrates |
| IL112248A0 (en) * | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| AU732863B2 (en) * | 1997-04-18 | 2001-05-03 | Smithkline Beecham Plc | Indole derivatives having combined 5HT1A, 5HT1B and 5HT1D receptor antagonist activity |
| WO1998047868A1 (en) * | 1997-04-18 | 1998-10-29 | Smithkline Beecham Plc | Heterocycle-containing urea derivatives as 5ht1a, 5ht1b and 5ht1d receptor antagonists |
| WO1999018077A1 (en) * | 1997-10-02 | 1999-04-15 | Eisai Co., Ltd. | Fused pyridine derivatives |
| JP2002508366A (ja) * | 1997-12-12 | 2002-03-19 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | キノリンピペラジンおよびキノリンピペリジン誘導体、それらの製造方法、ならびに複合的５−ｈｔ１ａ、５−ｈｔ１ｂおよび５−ｈｔ１ｄ受容体アンタゴニストとしてのそれらの用途 |
| WO2000006575A2 (en) * | 1998-07-28 | 2000-02-10 | Smithkline Beecham Plc | Azabicyclic compounds |
-
2000
- 2000-11-02 EP EP00971423A patent/EP1228043B1/en not_active Expired - Lifetime
- 2000-11-02 AT AT00971423T patent/ATE286883T1/de not_active IP Right Cessation
- 2000-11-02 JP JP2001534778A patent/JP2003513075A/ja active Pending
- 2000-11-02 AU AU10286/01A patent/AU1028601A/en not_active Abandoned
- 2000-11-02 DE DE60017446T patent/DE60017446T2/de not_active Expired - Fee Related
- 2000-11-02 WO PCT/EP2000/010908 patent/WO2001032626A1/en not_active Ceased
- 2000-11-02 ES ES00971423T patent/ES2234683T3/es not_active Expired - Lifetime
- 2000-11-03 PE PE2000001176A patent/PE20010956A1/es not_active Application Discontinuation
- 2000-11-03 UY UY26426A patent/UY26426A1/es not_active Application Discontinuation
-
2005
- 2005-06-13 US US11/151,008 patent/US20050239797A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| ES2234683T3 (es) | 2005-07-01 |
| WO2001032626A1 (en) | 2001-05-10 |
| EP1228043B1 (en) | 2005-01-12 |
| PE20010956A1 (es) | 2001-09-15 |
| UY26426A1 (es) | 2001-05-31 |
| AU1028601A (en) | 2001-05-14 |
| US20050239797A1 (en) | 2005-10-27 |
| EP1228043A1 (en) | 2002-08-07 |
| JP2003513075A (ja) | 2003-04-08 |
| ATE286883T1 (de) | 2005-01-15 |
| DE60017446D1 (de) | 2005-02-17 |
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