CA1249269A - Benzodiazepines, processes for their preparation and their use - Google Patents
Benzodiazepines, processes for their preparation and their useInfo
- Publication number
- CA1249269A CA1249269A CA000489254A CA489254A CA1249269A CA 1249269 A CA1249269 A CA 1249269A CA 000489254 A CA000489254 A CA 000489254A CA 489254 A CA489254 A CA 489254A CA 1249269 A CA1249269 A CA 1249269A
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- chloro
- spiro
- piperidin
- acceptable salt
- 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
Links
- 229940049706 benzodiazepine Drugs 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract description 14
- 230000008569 process Effects 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 150000001557 benzodiazepines Chemical class 0.000 title abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 33
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 96
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 46
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 37
- 229910052731 fluorine Inorganic materials 0.000 claims description 28
- -1 6-membered hetero-cyclic radical Chemical class 0.000 claims description 27
- 229910052794 bromium Inorganic materials 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 25
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 23
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 238000005804 alkylation reaction Methods 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 230000029936 alkylation Effects 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 150000003254 radicals Chemical class 0.000 claims description 5
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- 125000004429 atom Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- PLPMGHXRBOJVHR-UHFFFAOYSA-N 4-amino-1-benzylpiperidine-4-carbonyl chloride;dihydrochloride Chemical compound Cl.Cl.C1CC(N)(C(Cl)=O)CCN1CC1=CC=CC=C1 PLPMGHXRBOJVHR-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
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- UMPFWXKTYANUAO-UHFFFAOYSA-N 1'-benzyl-7-chloro-1-methyl-5-phenylspiro[1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound O=C1N(C)C2=CC=C(Cl)C=C2C(C=2C=CC=CC=2)=NC1(CC1)CCN1CC1=CC=CC=C1 UMPFWXKTYANUAO-UHFFFAOYSA-N 0.000 claims 2
- HOIDHMTWECEBAF-UHFFFAOYSA-N 1'-benzyl-7-chloro-5-phenylspiro[1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N1=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2NC(=O)C1(CC1)CCN1CC1=CC=CC=C1 HOIDHMTWECEBAF-UHFFFAOYSA-N 0.000 claims 2
- DULSJKXBUGUHOI-UHFFFAOYSA-N 7-chloro-1',4-dimethyl-5-phenylspiro[1,5-dihydro-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound C1CN(C)CCC21C(=O)NC1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)N2C DULSJKXBUGUHOI-UHFFFAOYSA-N 0.000 claims 2
- BBZDURHUDVJOMJ-UHFFFAOYSA-N 7-chloro-1'-methyl-5-phenylspiro[4,5-dihydro-1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound C1CN(C)CCC21C(=O)NC1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)N2 BBZDURHUDVJOMJ-UHFFFAOYSA-N 0.000 claims 2
- HUZLOWKVQBKMCB-UHFFFAOYSA-N 7-chloro-1,1',4-trimethyl-5-phenylspiro[5h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound C1CN(C)CCC21C(=O)N(C)C1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)N2C HUZLOWKVQBKMCB-UHFFFAOYSA-N 0.000 claims 2
- DNTOCGRDWRDLQX-UHFFFAOYSA-N 7-chloro-1,1'-dimethyl-5-phenylspiro[4,5-dihydro-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound C1CN(C)CCC21C(=O)N(C)C1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)N2 DNTOCGRDWRDLQX-UHFFFAOYSA-N 0.000 claims 2
- JHLASPMQEQHGJC-UHFFFAOYSA-N 7-chloro-1-ethyl-5-phenylspiro[4,5-dihydro-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound O=C1N(CC)C2=CC=C(Cl)C=C2C(C=2C=CC=CC=2)NC21CCNCC2 JHLASPMQEQHGJC-UHFFFAOYSA-N 0.000 claims 2
- ZJIIWKMQNNHOCS-UHFFFAOYSA-N 7-chloro-5-phenylspiro[1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N1=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2NC(=O)C21CCNCC2 ZJIIWKMQNNHOCS-UHFFFAOYSA-N 0.000 claims 2
- VHTGMXAERGPNGV-UHFFFAOYSA-N 7-chloro-5-phenylspiro[4,5-dihydro-1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound N1C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2NC(=O)C21CCNCC2 VHTGMXAERGPNGV-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- JBKFVAVNIDDFFD-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-(4-chlorophenyl)methanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=C(Cl)C=C1 JBKFVAVNIDDFFD-UHFFFAOYSA-N 0.000 claims 1
- OIHCPMHJUCEIBG-UHFFFAOYSA-N 1'-benzyl-5-methylspiro[1H-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical group O=C1NC2=CC=CC=C2C(C)=NC1(CC1)CCN1CC1=CC=CC=C1 OIHCPMHJUCEIBG-UHFFFAOYSA-N 0.000 claims 1
- AJSZCJYOEGCKQB-UHFFFAOYSA-N 1'-benzyl-7-chloro-5-(4-chlorophenyl)spiro[1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound C1=CC(Cl)=CC=C1C(C1=CC(Cl)=CC=C1NC1=O)=NC11CCN(CC=2C=CC=CC=2)CC1 AJSZCJYOEGCKQB-UHFFFAOYSA-N 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- SFGCCFUULMZVND-UHFFFAOYSA-N 7-chloro-1'-methyl-5-phenylspiro[1h-1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound C1CN(C)CCC21C(=O)NC1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)=N2 SFGCCFUULMZVND-UHFFFAOYSA-N 0.000 claims 1
- PHPKWPGXEDJLKG-UHFFFAOYSA-N 7-chloro-1,1'-dimethyl-5-phenylspiro[1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound C1CN(C)CCC21C(=O)N(C)C1=CC=C(Cl)C=C1C(C=1C=CC=CC=1)=N2 PHPKWPGXEDJLKG-UHFFFAOYSA-N 0.000 claims 1
- WDLSJVRXVPVVAL-UHFFFAOYSA-N 7-chloro-1-methyl-5-phenylspiro[1,4-benzodiazepine-3,4'-piperidine]-2-one Chemical compound O=C1N(C)C2=CC=C(Cl)C=C2C(C=2C=CC=CC=2)=NC21CCNCC2 WDLSJVRXVPVVAL-UHFFFAOYSA-N 0.000 claims 1
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Classifications
-
- 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
- C07D471/10—Spiro-condensed systems
-
- 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
- A61P25/28—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843431195 DE3431195A1 (de) | 1984-08-24 | 1984-08-24 | Neue benzodiazepine, verfahren zu ihrer herstellung sowie ihre verwendung |
| DEP3431195.5 | 1984-08-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1249269A true CA1249269A (en) | 1989-01-24 |
Family
ID=6243820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000489254A Expired CA1249269A (en) | 1984-08-24 | 1985-08-22 | Benzodiazepines, processes for their preparation and their use |
Country Status (19)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4957915A (en) * | 1989-02-27 | 1990-09-18 | Biomeasure, Inc. | Benzodiazepine analogs |
| CA2160786A1 (en) * | 1993-05-14 | 1994-11-24 | James C. Marsters, Jr. | Ras farnesyl transferase inhibitors |
| CA2469879A1 (en) * | 2001-12-14 | 2003-06-26 | Merck & Co. Inc. | A novel sordarin derivative isolated from culture fermentations and functions as an antifungal agent |
| EP1591120A4 (en) * | 2003-01-28 | 2009-06-10 | Takeda Chemical Industries Ltd | RECEPTOR AGONISTS |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3998811A (en) * | 1971-03-17 | 1976-12-21 | Crc Compagnia Di Recerca Chimica S.A. | Optically active 1,4-benzodiazepines and process for the preparation thereof |
| HU171033B (hu) * | 1974-05-29 | 1977-10-28 | Richter Gedeon Vegyeszet | Sposob poluchenija proizvodnykh benzodiazepina |
| CA1157855A (en) * | 1980-07-31 | 1983-11-29 | Albert E. Fischli | Benzodiazepine derivatives |
| NL8401907A (nl) * | 1983-06-27 | 1985-01-16 | Sandoz Ag | Spirosuccinimiden en werkwijzen voor het bereiden en toepassen van deze spirosuccinimiden. |
-
1984
- 1984-08-24 DE DE19843431195 patent/DE3431195A1/de not_active Withdrawn
-
1985
- 1985-08-05 NO NO853089A patent/NO161494C/no unknown
- 1985-08-08 US US06/763,746 patent/US4647560A/en not_active Expired - Fee Related
- 1985-08-14 AT AT85110191T patent/ATE46905T1/de not_active IP Right Cessation
- 1985-08-14 EP EP85110191A patent/EP0172526B1/de not_active Expired
- 1985-08-14 DE DE8585110191T patent/DE3573425D1/de not_active Expired
- 1985-08-21 PH PH32676A patent/PH23803A/en unknown
- 1985-08-21 NZ NZ213186A patent/NZ213186A/en unknown
- 1985-08-21 IL IL76153A patent/IL76153A0/xx not_active IP Right Cessation
- 1985-08-22 CA CA000489254A patent/CA1249269A/en not_active Expired
- 1985-08-22 GR GR852035A patent/GR852035B/el unknown
- 1985-08-22 FI FI853229A patent/FI79315C/fi not_active IP Right Cessation
- 1985-08-22 AU AU46574/85A patent/AU574216B2/en not_active Ceased
- 1985-08-22 PT PT81003A patent/PT81003B/pt not_active IP Right Cessation
- 1985-08-23 HU HU853222A patent/HU201933B/hu not_active IP Right Cessation
- 1985-08-23 ZA ZA856409A patent/ZA856409B/xx unknown
- 1985-08-23 ES ES546378A patent/ES8702910A1/es not_active Expired
- 1985-08-23 KR KR1019850006080A patent/KR920000763B1/ko not_active Expired
- 1985-08-23 JP JP60184317A patent/JPS6157582A/ja active Granted
- 1985-08-23 DK DK384585A patent/DK384585A/da not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0172526A1 (de) | 1986-02-26 |
| DK384585D0 (da) | 1985-08-23 |
| FI853229L (fi) | 1986-02-25 |
| KR920000763B1 (ko) | 1992-01-21 |
| PH23803A (en) | 1989-11-03 |
| ES8702910A1 (es) | 1987-01-16 |
| JPS6157582A (ja) | 1986-03-24 |
| GR852035B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1985-12-18 |
| PT81003A (en) | 1985-09-01 |
| ZA856409B (en) | 1986-04-30 |
| US4647560A (en) | 1987-03-03 |
| NO161494C (no) | 1989-08-23 |
| AU574216B2 (en) | 1988-06-30 |
| FI79315B (fi) | 1989-08-31 |
| DE3431195A1 (de) | 1986-03-06 |
| DE3573425D1 (en) | 1989-11-09 |
| NO853089L (no) | 1986-02-25 |
| JPH0378868B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-12-17 |
| HU201933B (en) | 1991-01-28 |
| PT81003B (pt) | 1987-12-30 |
| ES546378A0 (es) | 1987-01-16 |
| DK384585A (da) | 1986-02-25 |
| HUT39449A (en) | 1986-09-29 |
| EP0172526B1 (de) | 1989-10-04 |
| FI853229A0 (fi) | 1985-08-22 |
| NZ213186A (en) | 1988-04-29 |
| KR860001812A (ko) | 1986-03-22 |
| IL76153A0 (en) | 1985-12-31 |
| FI79315C (fi) | 1989-12-11 |
| ATE46905T1 (de) | 1989-10-15 |
| AU4657485A (en) | 1986-02-27 |
| NO161494B (no) | 1989-05-16 |
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| MKEX | Expiry |