DE69109125T2 - Ringverknüpfte analoge von stickstoffenthaltenden nichtaromatischen heterocyclen. - Google Patents
Ringverknüpfte analoge von stickstoffenthaltenden nichtaromatischen heterocyclen.Info
- Publication number
- DE69109125T2 DE69109125T2 DE69109125T DE69109125T DE69109125T2 DE 69109125 T2 DE69109125 T2 DE 69109125T2 DE 69109125 T DE69109125 T DE 69109125T DE 69109125 T DE69109125 T DE 69109125T DE 69109125 T2 DE69109125 T2 DE 69109125T2
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- phenyl
- compound
- amino
- azabicyclo
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 185
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 23
- -1 benzhydryl groups Chemical group 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
- 239000000460 chlorine Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 150000001721 carbon Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- DELMNZCZSVHTAK-UHFFFAOYSA-N 4-benzhydryl-n-[(2-methoxyphenyl)methyl]-3-azabicyclo[4.1.0]heptan-5-amine Chemical compound COC1=CC=CC=C1CNC1C(C(C=2C=CC=CC=2)C=2C=CC=CC=2)NCC2CC21 DELMNZCZSVHTAK-UHFFFAOYSA-N 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 239000005864 Sulphur Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- HNXPMXNINBNHHK-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-2-phenyl-1,2,3,4,4a,5,6,7,8,8a-decahydroquinolin-3-amine Chemical compound COC1=CC=CC=C1CNC1C(C=2C=CC=CC=2)NC2CCCCC2C1 HNXPMXNINBNHHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- BNVSOBVEYPBNFE-PKTZIBPZSA-N (3s,4r)-4-[(2-methoxyphenyl)methylamino]-2-methyl-3-phenyl-3,4-dihydroisoquinolin-1-one Chemical compound COC1=CC=CC=C1CN[C@@H]1C2=CC=CC=C2C(=O)N(C)[C@H]1C1=CC=CC=C1 BNVSOBVEYPBNFE-PKTZIBPZSA-N 0.000 claims description 2
- YHHXYOYYXFVZIM-FCHUYYIVSA-N (3s,4r)-4-[(2-methoxyphenyl)methylamino]-3-phenyl-3,4-dihydro-2h-isoquinolin-1-one Chemical compound COC1=CC=CC=C1CN[C@@H]1C2=CC=CC=C2C(=O)N[C@H]1C1=CC=CC=C1 YHHXYOYYXFVZIM-FCHUYYIVSA-N 0.000 claims description 2
- CYAMCEFBULMVSA-RPWUZVMVSA-N (3s,4r)-n-[(2-methoxyphenyl)methyl]-2-methyl-3-phenyl-3,4-dihydro-1h-isoquinolin-4-amine Chemical compound COC1=CC=CC=C1CN[C@@H]1C2=CC=CC=C2CN(C)[C@H]1C1=CC=CC=C1 CYAMCEFBULMVSA-RPWUZVMVSA-N 0.000 claims description 2
- OKHIQWVGAJUEIY-GIQPFHSMSA-N (3s,4r)-n-[(2-methoxyphenyl)methyl]-3-phenyl-1,2,3,4-tetrahydroisoquinolin-4-amine;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC=C1CN[C@@H]1C2=CC=CC=C2CN[C@H]1C1=CC=CC=C1 OKHIQWVGAJUEIY-GIQPFHSMSA-N 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- RAPYEQWTEDGYLB-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-2-phenyl-1,2,3,4-tetrahydroquinolin-3-amine Chemical compound COC1=CC=CC=C1CNC1C(C=2C=CC=CC=2)NC2=CC=CC=C2C1 RAPYEQWTEDGYLB-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical group FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims 2
- WKYFCYXOJUSICF-UHFFFAOYSA-N 3-benzhydryl-n-[(2-methoxyphenyl)methyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinolin-4-amine Chemical compound COC1=CC=CC=C1CNC1C(C(C=2C=CC=CC=2)C=2C=CC=CC=2)NCC2CCCCC21 WKYFCYXOJUSICF-UHFFFAOYSA-N 0.000 claims 1
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 17
- 208000027866 inflammatory disease Diseases 0.000 abstract description 4
- 208000015114 central nervous system disease Diseases 0.000 abstract description 2
- 230000002757 inflammatory effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 116
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 238000000034 method Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 239000005909 Kieselgur Substances 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 239000002798 polar solvent Substances 0.000 description 12
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 11
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- 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
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Eye Examination Apparatus (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Electroluminescent Light Sources (AREA)
- Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59042390A | 1990-09-28 | 1990-09-28 | |
| PCT/US1991/005776 WO1992006079A1 (en) | 1990-09-28 | 1991-08-20 | Fused ring analogs of nitrogen containing nonaromatic heterocycles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69109125D1 DE69109125D1 (de) | 1995-05-24 |
| DE69109125T2 true DE69109125T2 (de) | 1995-09-28 |
Family
ID=24362216
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69109125T Expired - Fee Related DE69109125T2 (de) | 1990-09-28 | 1991-08-20 | Ringverknüpfte analoge von stickstoffenthaltenden nichtaromatischen heterocyclen. |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0550635B1 (enExample) |
| JP (1) | JPH0772175B2 (enExample) |
| CN (1) | CN1060285A (enExample) |
| AT (1) | ATE121389T1 (enExample) |
| AU (1) | AU651145B2 (enExample) |
| BR (1) | BR9106905A (enExample) |
| CA (1) | CA2089736A1 (enExample) |
| CZ (1) | CZ387492A3 (enExample) |
| DE (1) | DE69109125T2 (enExample) |
| DK (1) | DK0550635T3 (enExample) |
| ES (1) | ES2071334T3 (enExample) |
| FI (1) | FI931370A0 (enExample) |
| HU (1) | HUT68667A (enExample) |
| IE (1) | IE66042B1 (enExample) |
| IL (1) | IL99525A0 (enExample) |
| MX (1) | MX9101274A (enExample) |
| NO (1) | NO931151L (enExample) |
| PT (1) | PT99064A (enExample) |
| TW (1) | TW199144B (enExample) |
| WO (1) | WO1992006079A1 (enExample) |
| YU (1) | YU159291A (enExample) |
| ZA (1) | ZA917744B (enExample) |
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| US5716965A (en) * | 1991-05-22 | 1998-02-10 | Pfizer Inc. | Substituted 3-aminoquinuclidines |
| BR9206161A (pt) * | 1991-06-20 | 1995-10-31 | Pfizer | Derivados fluoroalcoxibenzilamino de heterociclos contendo nitrogénio |
| TW202432B (enExample) * | 1991-06-21 | 1993-03-21 | Pfizer | |
| MY110227A (en) * | 1991-08-12 | 1998-03-31 | Ciba Geigy Ag | 1-acylpiperindine compounds. |
| PT533280E (pt) * | 1991-09-20 | 2001-01-31 | Glaxo Group Ltd | Novas utilizacoes medicas para antagonistas de taquiquinina |
| DK0613458T3 (da) * | 1991-11-12 | 1998-02-09 | Pfizer | Acykliske ethylendiaminderivater som substans P receptorantagonister |
| CA2134964C (en) * | 1992-05-18 | 1997-12-30 | Manoj C. Desai | Bridged aza-bicyclic derivatives as substance p antagonists |
| US5637699A (en) * | 1992-06-29 | 1997-06-10 | Merck & Co., Inc. | Process for preparing morpholine tachykinin receptor antagonists |
| US5719147A (en) * | 1992-06-29 | 1998-02-17 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| US6048859A (en) * | 1992-06-29 | 2000-04-11 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| CA2141051A1 (en) * | 1992-08-04 | 1994-02-17 | Terry J. Rosen | Substituted nitrogen-containing heterocycles |
| GB9216911D0 (en) * | 1992-08-10 | 1992-09-23 | Merck Sharp & Dohme | Therapeutic agents |
| EP1114823A3 (en) * | 1992-08-19 | 2001-07-18 | Pfizer Inc. | Substituted benzylamino nitrogen containing non-aromatic heterocycles |
| US5387595A (en) * | 1992-08-26 | 1995-02-07 | Merck & Co., Inc. | Alicyclic compounds as tachykinin receptor antagonists |
| US5344830A (en) * | 1992-12-10 | 1994-09-06 | Merck & Co., Inc. | N,N-diacylpiperazine tachykinin antagonists |
| PT675886E (pt) * | 1992-12-10 | 2000-12-29 | Pfizer | Heterociclos nao aromaticos com substituintes aminometileno e sua utilizacao como antagonistas da substancia p |
| US5830854A (en) * | 1992-12-14 | 1998-11-03 | Merck Sharp & Dohme, Limited | Method of treating cystic fibrosis using a tachykinin receptor antagonist |
| US5340826A (en) * | 1993-02-04 | 1994-08-23 | Pfizer Inc. | Pharmaceutical agents for treatment of urinary incontinence |
| US5393762A (en) * | 1993-06-04 | 1995-02-28 | Pfizer Inc. | Pharmaceutical agents for treatment of emesis |
| US5854262A (en) * | 1993-10-07 | 1998-12-29 | Pfizer Inc. | Aminomethylene substituted non-aromatic heterocycles and use as substance P antagonists |
| US5610165A (en) * | 1994-02-17 | 1997-03-11 | Merck & Co., Inc. | N-acylpiperidine tachykinin antagonists |
| IL112778A0 (en) * | 1994-03-04 | 1995-05-26 | Merck & Co Inc | Substituted heterocycles, their preparation and pharmaceutical compositions containing them |
| TW397825B (en) * | 1994-10-14 | 2000-07-11 | Novartis Ag | Aroyl-piperidine derivatives |
| FR2725900B1 (fr) * | 1994-10-21 | 1997-07-18 | Sanofi Sa | Utilisation d'antagonistes des recepteurs nk1 pour la preparation de medicaments a action cardioregulatrice |
| TW458774B (en) | 1995-10-20 | 2001-10-11 | Pfizer | Antiemetic pharmaceutical compositions |
| US6245817B1 (en) | 1997-02-14 | 2001-06-12 | Bayer Corporation | NPY5 receptor antagonists and methods for using same |
| JP2000510870A (ja) * | 1997-02-14 | 2000-08-22 | バイエル・コーポレーシヨン | Ｎｐｙ５受容体アンタゴニストとしてのアミド類 |
| US6048900A (en) * | 1998-02-13 | 2000-04-11 | Bayer Corporation | Amide derivatives and methods for using the same as selective neuropeptide Y receptor antagonists |
| EP0910565A1 (en) * | 1997-02-14 | 1999-04-28 | Bayer Corporation | Amide derivatives as selective neuropeptide y receptor antagonists |
| ATE387429T1 (de) | 1999-11-03 | 2008-03-15 | Amr Technology Inc | Arly- und heteroaryl-substituierte tetrahydroisoquinoline und ihre verwendung als hemmer der wiederaufnahme von norepinephrin, dopamin und serotonin |
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| EA005409B1 (ru) * | 2000-04-10 | 2005-02-24 | Пфайзер Продактс Инк. | Производные бензамидопиперидина в качестве антагонистов рецепторов вещества p |
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| CN101119969B (zh) | 2004-07-15 | 2014-04-09 | 阿尔巴尼分子研究公司 | 芳基和杂芳基取代的四氢异喹啉及其阻断去甲肾上腺素、多巴胺和血清素的重摄取的应用 |
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| DE102005027168A1 (de) * | 2005-06-13 | 2006-12-14 | Merck Patent Gmbh | Tetrahydrochinoline |
| EA019115B1 (ru) | 2005-07-15 | 2014-01-30 | Олбани Молекьюлар Рисерч, Инк. | Арил- и гетероарилзамещенные тетрагидробензазепины и их применение для блокировки обратного захвата норэпинефрина, допамина и серотонина |
| KR20080048502A (ko) | 2005-09-29 | 2008-06-02 | 머크 앤드 캄파니 인코포레이티드 | 멜라노코르틴-4 수용체 조절제로서의 아실화스피로피페리딘 유도체 |
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| GB0617867D0 (en) * | 2006-09-11 | 2006-10-18 | Glaxo Group Ltd | Chemical compounds |
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| US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
| GEP20115337B (en) | 2007-01-10 | 2011-11-25 | St Di Ricerche Di Biologia Molecolare P Angeletti Spa | Amide substituted indazoles as poly(adp-ribose)polymerase (parp) inhibitors |
| WO2008090114A1 (en) | 2007-01-24 | 2008-07-31 | Glaxo Group Limited | Pharmaceutical compositions comprising 2-methoxy-5- (5-trifluoromethyl-tetrazol-i-yl-benzyl) - (2s-phenyl-piperidin-3s-yl-) |
| JP5319518B2 (ja) | 2007-04-02 | 2013-10-16 | Ｍｓｄ株式会社 | インドールジオン誘導体 |
| AU2008269154B2 (en) | 2007-06-27 | 2014-06-12 | Merck Sharp & Dohme Llc | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
| GB0716573D0 (en) * | 2007-08-24 | 2007-10-03 | Glaxo Group Ltd | Chemical compounds |
| US8598184B2 (en) | 2008-03-03 | 2013-12-03 | Tiger Pharmatech | Protein kinase inhibitors |
| GB0804326D0 (en) * | 2008-03-07 | 2008-04-16 | Glaxo Group Ltd | Novel compounds |
| AR071997A1 (es) | 2008-06-04 | 2010-07-28 | Bristol Myers Squibb Co | Forma cristalina de 6-((4s)-2-metil-4-(2-naftil)-1,2,3,4-tetrahidroisoquinolin-7-il)piridazin-3-amina |
| US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
| UA105182C2 (ru) | 2008-07-03 | 2014-04-25 | Ньюрексон, Інк. | Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность |
| WO2010114780A1 (en) | 2009-04-01 | 2010-10-07 | Merck Sharp & Dohme Corp. | Inhibitors of akt activity |
| MX2011011900A (es) | 2009-05-12 | 2012-01-20 | Squibb Bristol Myers Co | Formas cristalinas de (s)-7-([1,2,4]triazolo[1,5-a]piridin-6-il)-4 -(3,4-diclorofenil)-1,2,3,4-tetrahidroisoquinolina y usos de las misma. |
| CN102595902B (zh) | 2009-05-12 | 2015-04-29 | 阿尔巴尼分子研究公司 | 7-([1,2,4]三唑并[1,5-a]吡啶-6-基)-4-(3,4-二氯苯基)-1,2,3,4-四氢异喹啉及其用途 |
| WO2010132437A1 (en) | 2009-05-12 | 2010-11-18 | Albany Molecular Research, Inc. | Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof |
| MY174452A (en) | 2009-10-14 | 2020-04-19 | Schering Corp | Substituted piperidines that increase p53 activity and the uses thereof |
| US8999957B2 (en) | 2010-06-24 | 2015-04-07 | Merck Sharp & Dohme Corp. | Heterocyclic compounds as ERK inhibitors |
| US8518907B2 (en) | 2010-08-02 | 2013-08-27 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) gene expression using short interfering nucleic acid (siNA) |
| EP3587574B1 (en) | 2010-08-17 | 2022-03-16 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina) |
| US8883801B2 (en) | 2010-08-23 | 2014-11-11 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as mTOR inhibitors |
| US8946216B2 (en) | 2010-09-01 | 2015-02-03 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as ERK inhibitors |
| US9242981B2 (en) | 2010-09-16 | 2016-01-26 | Merck Sharp & Dohme Corp. | Fused pyrazole derivatives as novel ERK inhibitors |
| US9260471B2 (en) | 2010-10-29 | 2016-02-16 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acids (siNA) |
| EP2654748B1 (en) | 2010-12-21 | 2016-07-27 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as erk inhibitors |
| CA2833009A1 (en) | 2011-04-21 | 2012-10-26 | Merck Sharp & Dohme Corp. | Insulin-like growth factor-1 receptor inhibitors |
| US9023865B2 (en) | 2011-10-27 | 2015-05-05 | Merck Sharp & Dohme Corp. | Compounds that are ERK inhibitors |
| EP3919620A1 (en) | 2012-05-02 | 2021-12-08 | Sirna Therapeutics, Inc. | Short interfering nucleic acid (sina) compositions |
| JP6280554B2 (ja) | 2012-09-28 | 2018-02-14 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｅｒｋ阻害剤である新規化合物 |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| DK2925888T3 (en) | 2012-11-28 | 2017-12-18 | Merck Sharp & Dohme | COMPOSITIONS AND METHODS OF CANCER TREATMENT |
| AR094116A1 (es) | 2012-12-20 | 2015-07-08 | Merck Sharp & Dohme | Imidazopiridinas sustituidas como inhibidores de hdm2 |
| WO2014120748A1 (en) | 2013-01-30 | 2014-08-07 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as hdm2 inhibitors |
| US20160194368A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Circular polynucleotides |
| CN104610146A (zh) * | 2015-01-23 | 2015-05-13 | 常州大学 | 一种3-氮杂二环[5,1,0]-7-醛及合成方法 |
| CN105330588B (zh) * | 2015-10-16 | 2017-09-26 | 辽宁中医药大学 | 马齿苋中生物碱Oleracone及其提取分离方法 |
| EP3525785B1 (en) | 2016-10-12 | 2025-08-27 | Merck Sharp & Dohme LLC | Kdm5 inhibitors |
| EP3706747B1 (en) | 2017-11-08 | 2025-09-03 | Merck Sharp & Dohme LLC | Prmt5 inhibitors |
| US10947234B2 (en) | 2017-11-08 | 2021-03-16 | Merck Sharp & Dohme Corp. | PRMT5 inhibitors |
| WO2020033284A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
| US11993602B2 (en) | 2018-08-07 | 2024-05-28 | Merck Sharp & Dohme Llc | PRMT5 inhibitors |
| EP3833355A4 (en) | 2018-08-07 | 2022-05-11 | Merck Sharp & Dohme Corp. | PRMT5 INHIBITORS |
| CN113121427B (zh) * | 2021-03-19 | 2022-04-01 | 广东工业大学 | 一种喹啉类衍生物及其制备方法和应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3452026A (en) * | 1966-03-15 | 1969-06-24 | Bristol Myers Co | Substituted 1,2,3,4-tetrahydroquinolines |
| FR1555552A (enExample) * | 1967-07-05 | 1969-01-31 | ||
| US4198415A (en) * | 1979-01-22 | 1980-04-15 | Eli Lilly And Company | Prolactin inhibiting octahydro pyrazolo[3,4-g]quinolines |
| MX18467A (es) * | 1988-11-23 | 1993-07-01 | Pfizer | Agentes terapeuticos de quinuclidinas |
-
1991
- 1991-08-20 ES ES91918058T patent/ES2071334T3/es not_active Expired - Lifetime
- 1991-08-20 CZ CS923874A patent/CZ387492A3/cs unknown
- 1991-08-20 JP JP3517076A patent/JPH0772175B2/ja not_active Expired - Fee Related
- 1991-08-20 DK DK91918058.8T patent/DK0550635T3/da active
- 1991-08-20 BR BR919106905A patent/BR9106905A/pt not_active Application Discontinuation
- 1991-08-20 EP EP91918058A patent/EP0550635B1/en not_active Expired - Lifetime
- 1991-08-20 AU AU87463/91A patent/AU651145B2/en not_active Expired - Fee Related
- 1991-08-20 CA CA002089736A patent/CA2089736A1/en not_active Abandoned
- 1991-08-20 WO PCT/US1991/005776 patent/WO1992006079A1/en not_active Ceased
- 1991-08-20 DE DE69109125T patent/DE69109125T2/de not_active Expired - Fee Related
- 1991-08-20 FI FI931370A patent/FI931370A0/fi not_active Application Discontinuation
- 1991-08-20 HU HU9300898A patent/HUT68667A/hu unknown
- 1991-08-20 AT AT91918058T patent/ATE121389T1/de not_active IP Right Cessation
- 1991-08-23 TW TW080106710A patent/TW199144B/zh active
- 1991-09-19 IL IL99525A patent/IL99525A0/xx unknown
- 1991-09-26 MX MX9101274A patent/MX9101274A/es unknown
- 1991-09-26 PT PT99064A patent/PT99064A/pt not_active Application Discontinuation
- 1991-09-27 CN CN91109446A patent/CN1060285A/zh active Pending
- 1991-09-27 IE IE339691A patent/IE66042B1/en not_active IP Right Cessation
- 1991-09-27 YU YU159291A patent/YU159291A/sh unknown
- 1991-09-27 ZA ZA917744A patent/ZA917744B/xx unknown
-
1993
- 1993-03-26 NO NO93931151A patent/NO931151L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| FI931370A7 (fi) | 1993-03-26 |
| CN1060285A (zh) | 1992-04-15 |
| IE913396A1 (en) | 1992-04-08 |
| HU9300898D0 (en) | 1993-06-28 |
| ES2071334T3 (es) | 1995-06-16 |
| ZA917744B (en) | 1993-03-29 |
| JPH06501267A (ja) | 1994-02-10 |
| IL99525A0 (en) | 1992-08-18 |
| BR9106905A (pt) | 1993-08-17 |
| AU8746391A (en) | 1992-04-28 |
| AU651145B2 (en) | 1994-07-14 |
| EP0550635A1 (en) | 1993-07-14 |
| DK0550635T3 (da) | 1995-09-04 |
| YU159291A (sh) | 1994-01-20 |
| HUT68667A (en) | 1995-07-28 |
| NO931151D0 (no) | 1993-03-26 |
| JPH0772175B2 (ja) | 1995-08-02 |
| FI931370L (fi) | 1993-03-26 |
| ATE121389T1 (de) | 1995-05-15 |
| WO1992006079A1 (en) | 1992-04-16 |
| CA2089736A1 (en) | 1992-03-29 |
| TW199144B (enExample) | 1993-02-01 |
| CZ387492A3 (en) | 1994-02-16 |
| DE69109125D1 (de) | 1995-05-24 |
| NO931151L (no) | 1993-03-26 |
| EP0550635B1 (en) | 1995-04-19 |
| PT99064A (pt) | 1992-08-31 |
| IE66042B1 (en) | 1995-12-13 |
| FI931370A0 (fi) | 1993-03-26 |
| MX9101274A (es) | 1992-05-04 |
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