CA2251335A1 - 3-[(1,2,3,4-tetrahydroisoquinoline-2-yl)methyl]-8-azabicyclo[3.2.1]octane derivatives, their preparation and their application in therapeutics - Google Patents
3-[(1,2,3,4-tetrahydroisoquinoline-2-yl)methyl]-8-azabicyclo[3.2.1]octane derivatives, their preparation and their application in therapeutics Download PDFInfo
- Publication number
- CA2251335A1 CA2251335A1 CA002251335A CA2251335A CA2251335A1 CA 2251335 A1 CA2251335 A1 CA 2251335A1 CA 002251335 A CA002251335 A CA 002251335A CA 2251335 A CA2251335 A CA 2251335A CA 2251335 A1 CA2251335 A1 CA 2251335A1
- Authority
- CA
- Canada
- Prior art keywords
- general formula
- compound
- azabicyclo
- group
- octane
- 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.)
- Abandoned
Links
- 238000002360 preparation method Methods 0.000 title claims description 4
- 239000003814 drug Substances 0.000 title description 2
- UECAYLDMIDGWPE-UHFFFAOYSA-N 2-(8-azabicyclo[3.2.1]octan-3-ylmethyl)-3,4-dihydro-1h-isoquinoline Chemical class C1CC2=CC=CC=C2CN1CC1CC(N2)CCC2C1 UECAYLDMIDGWPE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 100
- -1 2-methoxyethoxy Chemical group 0.000 claims abstract description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims abstract description 5
- 125000003277 amino group Chemical group 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 77
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 17
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 150000004678 hydrides Chemical class 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- ULEOLCZMLJKRNI-UHFFFAOYSA-N ethyl 8-benzyl-8-azabicyclo[3.2.1]octane-3-carboxylate Chemical compound C1C(C(=O)OCC)CC2CCC1N2CC1=CC=CC=C1 ULEOLCZMLJKRNI-UHFFFAOYSA-N 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
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- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
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- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
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- 229940126601 medicinal product Drugs 0.000 claims 1
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- 238000000926 separation method Methods 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
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- 239000003610 charcoal Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- OKMSDAJWJQUBIW-UHFFFAOYSA-N ethyl 3-(hydroxymethyl)-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(CO)CC2CCC1N2C(=O)OCC OKMSDAJWJQUBIW-UHFFFAOYSA-N 0.000 description 1
- YJJCYZSQHFBGQM-UHFFFAOYSA-N ethyl 3-[(4-methylphenyl)sulfonyloxymethyl]-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound CCOC(=O)N1C(C2)CCC1CC2COS(=O)(=O)C1=CC=C(C)C=C1 YJJCYZSQHFBGQM-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 238000012067 mathematical method Methods 0.000 description 1
- OIXMUQLVDNPHNS-UHFFFAOYSA-N methanesulfonic acid;hydrate Chemical compound O.CS(O)(=O)=O OIXMUQLVDNPHNS-UHFFFAOYSA-N 0.000 description 1
- JAXYJRAJHYCGOB-UHFFFAOYSA-N methyl 8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1CCC2CCC1N2C(=O)OC JAXYJRAJHYCGOB-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- TUNYMMOIJWPUHG-UHFFFAOYSA-N n,n-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide;hydrochloride Chemical compound Cl.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 TUNYMMOIJWPUHG-UHFFFAOYSA-N 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- ZHVULPDNOFUIML-UHFFFAOYSA-N octane;hydrochloride Chemical compound Cl.CCCCCCCC ZHVULPDNOFUIML-UHFFFAOYSA-N 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000009329 sexual behaviour Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetraline Natural products C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- YRYSAWZMIRQUBO-UHFFFAOYSA-N trimethylsulfoxonium Chemical class C[S+](C)(C)=O YRYSAWZMIRQUBO-UHFFFAOYSA-N 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR96/04565 | 1996-04-12 | ||
| FR9604565A FR2747386B1 (fr) | 1996-04-12 | 1996-04-12 | Derives de 3-[(1,2,3,4-tetrahydroisoquinolein-2-yl)methyl] -8-azabicyclo [3.2.1] octane, leur preparation et leur application en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2251335A1 true CA2251335A1 (en) | 1997-10-23 |
Family
ID=9491132
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002251335A Abandoned CA2251335A1 (en) | 1996-04-12 | 1997-04-10 | 3-[(1,2,3,4-tetrahydroisoquinoline-2-yl)methyl]-8-azabicyclo[3.2.1]octane derivatives, their preparation and their application in therapeutics |
Country Status (22)
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2303851A1 (en) * | 2008-06-27 | 2011-04-06 | H. Lundbeck A/S | Novel phenolic and catecholic amines and prodrugs thereof |
| US10870660B2 (en) | 2016-07-28 | 2020-12-22 | Shionogi & Co., Ltd. | Nitrogen-containing condensed ring compounds having dopamine D3 antagonistic effect |
| MX2020007849A (es) | 2018-01-26 | 2020-09-25 | Shionogi & Co | Compuesto ciclico condensado que tiene efecto antagonista del receptor de dopamina d3. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU895334D0 (en) * | 1986-07-30 | 1990-01-28 | Sandoz Ag | Process for the preparation of nasal pharmaceutical compositions |
| EP0306375A1 (fr) * | 1987-08-07 | 1989-03-08 | Synthelabo | Dérivés de[(pipéridinyl-4)méthyl]-2 tétrahydro-1,2,3,4 isoquinoléine, leur préparation et leur application en thérapeutique |
| IL89156A (en) * | 1988-07-12 | 1993-05-13 | Synthelabo | Derivatives of 2-((4-piperidinyl) methyl)- 1,2,3,4- tetrahydroisoquinoline, their preparation and their application in therapeutics |
| FR2661178B1 (fr) * | 1990-04-24 | 1993-03-12 | Synthelabo | Derives de [(tetrahydro-1,2,3,4 isoquinoleinyl-2)methyl]-4 piperidinecarboxylates-1 d'alkyle, leur preparation et leur application en therapeutique. |
-
1996
- 1996-04-12 FR FR9604565A patent/FR2747386B1/fr not_active Expired - Fee Related
-
1997
- 1997-04-10 CA CA002251335A patent/CA2251335A1/en not_active Abandoned
- 1997-04-10 CN CN97193750A patent/CN1216046A/zh active Pending
- 1997-04-10 SK SK1415-98A patent/SK141598A3/sk unknown
- 1997-04-10 KR KR1019980708123A patent/KR20000005392A/ko not_active Withdrawn
- 1997-04-10 AR ARP970101421A patent/AR008587A1/es unknown
- 1997-04-10 EE EE9800396A patent/EE9800396A/xx unknown
- 1997-04-10 PL PL97329243A patent/PL329243A1/xx unknown
- 1997-04-10 WO PCT/FR1997/000634 patent/WO1997038998A1/fr not_active Application Discontinuation
- 1997-04-10 EP EP97918195A patent/EP0892800A1/fr not_active Withdrawn
- 1997-04-10 NZ NZ332257A patent/NZ332257A/xx unknown
- 1997-04-10 CZ CZ983268A patent/CZ326898A3/cs unknown
- 1997-04-10 AU AU26409/97A patent/AU2640997A/en not_active Abandoned
- 1997-04-10 JP JP09536794A patent/JP2000512620A/ja active Pending
- 1997-04-10 TR TR1998/01839T patent/TR199801839T2/xx unknown
- 1997-04-10 BR BR9708654A patent/BR9708654A/pt not_active Application Discontinuation
- 1997-04-10 IL IL12647397A patent/IL126473A0/xx unknown
- 1997-04-10 TW TW086104625A patent/TW407158B/zh active
- 1997-04-11 CO CO97018806A patent/CO4900067A1/es unknown
- 1997-04-11 ZA ZA9703124A patent/ZA973124B/xx unknown
-
1998
- 1998-09-18 BG BG102779A patent/BG102779A/xx unknown
- 1998-10-09 NO NO984736A patent/NO984736L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NZ332257A (en) | 1999-03-29 |
| FR2747386B1 (fr) | 1998-05-15 |
| KR20000005392A (ko) | 2000-01-25 |
| AR008587A1 (es) | 2000-02-09 |
| CN1216046A (zh) | 1999-05-05 |
| IL126473A0 (en) | 1999-08-17 |
| TW407158B (en) | 2000-10-01 |
| SK141598A3 (en) | 1999-03-12 |
| PL329243A1 (en) | 1999-03-15 |
| NO984736D0 (no) | 1998-10-09 |
| FR2747386A1 (fr) | 1997-10-17 |
| CZ326898A3 (cs) | 1999-01-13 |
| EE9800396A (et) | 1999-06-15 |
| BR9708654A (pt) | 1999-08-03 |
| CO4900067A1 (es) | 2000-03-27 |
| JP2000512620A (ja) | 2000-09-26 |
| TR199801839T2 (enrdf_load_stackoverflow) | 1998-12-21 |
| EP0892800A1 (fr) | 1999-01-27 |
| BG102779A (en) | 1999-09-30 |
| NO984736L (no) | 1998-11-23 |
| WO1997038998A1 (fr) | 1997-10-23 |
| AU2640997A (en) | 1997-11-07 |
| ZA973124B (en) | 1997-11-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |