ES2226785T3 - Derivados de fenilurea como antagonistas de los receptores de orexina. - Google Patents
Derivados de fenilurea como antagonistas de los receptores de orexina.Info
- Publication number
- ES2226785T3 ES2226785T3 ES00906324T ES00906324T ES2226785T3 ES 2226785 T3 ES2226785 T3 ES 2226785T3 ES 00906324 T ES00906324 T ES 00906324T ES 00906324 T ES00906324 T ES 00906324T ES 2226785 T3 ES2226785 T3 ES 2226785T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- quinolinyl
- urea
- alkyl
- compound
- 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 - Lifetime
Links
- 239000005557 antagonist Substances 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 171
- 102000005962 receptors Human genes 0.000 claims abstract description 33
- 108020003175 receptors Proteins 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 101000598921 Homo sapiens Orexin Proteins 0.000 claims abstract description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000001301 oxygen Substances 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
- 239000011593 sulfur Substances 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- -1 2-methyl-4-quinolinyl Chemical group 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- VPMCCWRZRPCNOA-UHFFFAOYSA-N 1-(4-methyl-2-nitrophenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound [O-][N+](=O)C1=CC(C)=CC=C1NC(=O)NC1=CC(C)=NC2=CC=CC=C12 VPMCCWRZRPCNOA-UHFFFAOYSA-N 0.000 claims description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- DAVPQZYWZTXBJN-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-(3,4,5-trimethoxyphenyl)urea Chemical compound COC1=C(OC)C(OC)=CC(NC(=O)NC=2C3=CC=CC=C3N=C(C)C=2)=C1 DAVPQZYWZTXBJN-UHFFFAOYSA-N 0.000 claims description 4
- XKBRBZVPYWSNJA-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-(5,6,7,8-tetrahydronaphthalen-1-yl)urea Chemical compound C1=CC=CC2=NC(C)=CC(NC(=O)NC=3C=4CCCCC=4C=CC=3)=C21 XKBRBZVPYWSNJA-UHFFFAOYSA-N 0.000 claims description 4
- ISRXTIIGKBTICT-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-phenylurea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=CC=C1 ISRXTIIGKBTICT-UHFFFAOYSA-N 0.000 claims description 4
- HPZZLUMHLOCFLV-UHFFFAOYSA-N 1-(4-methylphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C1=CC(C)=CC=C1NC(=O)NC1=CC(C)=NC2=CC=CC=C12 HPZZLUMHLOCFLV-UHFFFAOYSA-N 0.000 claims description 4
- ROFZWQSOHVHHPY-UHFFFAOYSA-N 1-(6-methyl-2-oxo-1h-quinolin-4-yl)-3-phenylthiourea Chemical compound C12=CC(C)=CC=C2NC(=O)C=C1NC(=S)NC1=CC=CC=C1 ROFZWQSOHVHHPY-UHFFFAOYSA-N 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- CRCXAJCHYKBUJH-UHFFFAOYSA-N 1-(1-methylindol-5-yl)-3-(2-methylquinolin-4-yl)urea Chemical compound C1=CC=CC2=NC(C)=CC(NC(=O)NC=3C=C4C=CN(C)C4=CC=3)=C21 CRCXAJCHYKBUJH-UHFFFAOYSA-N 0.000 claims description 3
- SNNOGMLIXXEHLG-UHFFFAOYSA-N 1-(2,3-dichlorophenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=CC(Cl)=C1Cl SNNOGMLIXXEHLG-UHFFFAOYSA-N 0.000 claims description 3
- IETIBXVXLAXJIM-UHFFFAOYSA-N 1-(2-methoxyphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound COC1=CC=CC=C1NC(=O)NC1=CC(C)=NC2=CC=CC=C12 IETIBXVXLAXJIM-UHFFFAOYSA-N 0.000 claims description 3
- LTRWPUIMHSZSHR-UHFFFAOYSA-N 1-(2-methylphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=CC=C1C LTRWPUIMHSZSHR-UHFFFAOYSA-N 0.000 claims description 3
- JKWVVRXLBAMQLY-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-[3-(trifluoromethyl)phenyl]urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=CC(C(F)(F)F)=C1 JKWVVRXLBAMQLY-UHFFFAOYSA-N 0.000 claims description 3
- AVEATFGVCCGTSU-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=C(C)C(C)=C1 AVEATFGVCCGTSU-UHFFFAOYSA-N 0.000 claims description 3
- LFUYJGPVNJFZCN-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound CC1=CC(C)=CC(NC(=O)NC=2C3=CC=CC=C3N=C(C)C=2)=C1 LFUYJGPVNJFZCN-UHFFFAOYSA-N 0.000 claims description 3
- XGJCNQIEHUPXTE-UHFFFAOYSA-N 1-(3-chloro-4-methylphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=C(C)C(Cl)=C1 XGJCNQIEHUPXTE-UHFFFAOYSA-N 0.000 claims description 3
- JOTMLYFNAICCPR-UHFFFAOYSA-N 1-(3-hydroxyphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=CC(O)=C1 JOTMLYFNAICCPR-UHFFFAOYSA-N 0.000 claims description 3
- YZCQXNQZRRVTOG-UHFFFAOYSA-N 1-(3-methoxyphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound COC1=CC=CC(NC(=O)NC=2C3=CC=CC=C3N=C(C)C=2)=C1 YZCQXNQZRRVTOG-UHFFFAOYSA-N 0.000 claims description 3
- JQMQNDGGSXZDNL-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1=CC=C(Cl)C=C1 JQMQNDGGSXZDNL-UHFFFAOYSA-N 0.000 claims description 3
- AMNUXFGXHHMPGQ-UHFFFAOYSA-N 1-(4-methoxyphenyl)-3-(2-methylquinolin-4-yl)urea Chemical compound C1=CC(OC)=CC=C1NC(=O)NC1=CC(C)=NC2=CC=CC=C12 AMNUXFGXHHMPGQ-UHFFFAOYSA-N 0.000 claims description 3
- YBLWOZUPHDKFOT-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-(2-methyl-4-quinolinyl)urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC(C)=NC2=CC=CC=C12 YBLWOZUPHDKFOT-UHFFFAOYSA-N 0.000 claims description 3
- IKKJPORHYUTNHI-UHFFFAOYSA-N 1-[3-(dimethylamino)phenyl]-3-(2-methylquinolin-4-yl)urea Chemical compound CN(C)C1=CC=CC(NC(=O)NC=2C3=CC=CC=C3N=C(C)C=2)=C1 IKKJPORHYUTNHI-UHFFFAOYSA-N 0.000 claims description 3
- 229940123730 Orexin receptor antagonist Drugs 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 3
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- HLMVPRYBEVSPFB-UHFFFAOYSA-N 1-(6-amino-2-methylquinolin-4-yl)-3-(2-nitrophenyl)urea Chemical compound C=12C=C(N)C=CC2=NC(C)=CC=1NC(=O)NC1=CC=CC=C1[N+]([O-])=O HLMVPRYBEVSPFB-UHFFFAOYSA-N 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 abstract description 13
- 235000020824 obesity Nutrition 0.000 abstract description 13
- 125000001424 substituent group Chemical group 0.000 abstract description 13
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 abstract description 10
- 102000008834 Orexin receptor Human genes 0.000 abstract description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 abstract description 8
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 7
- 208000019116 sleep disease Diseases 0.000 abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 6
- 102000004877 Insulin Human genes 0.000 abstract description 4
- 108090001061 Insulin Proteins 0.000 abstract description 4
- FULZLIGZKMKICU-UHFFFAOYSA-N N-phenylthiourea Chemical class NC(=S)NC1=CC=CC=C1 FULZLIGZKMKICU-UHFFFAOYSA-N 0.000 abstract description 4
- 229940125396 insulin Drugs 0.000 abstract description 4
- 230000001419 dependent effect Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- 239000002253 acid Substances 0.000 description 67
- 239000002904 solvent Substances 0.000 description 55
- 239000000203 mixture Substances 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- 150000002148 esters Chemical class 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000008186 active pharmaceutical agent Substances 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000007787 solid Substances 0.000 description 27
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 208000002193 Pain Diseases 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 238000001914 filtration Methods 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000003446 ligand Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000012216 screening Methods 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000010561 standard procedure Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 8
- 102000002512 Orexin Human genes 0.000 description 7
- 125000002837 carbocyclic group Chemical group 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 208000004296 neuralgia Diseases 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 108060005714 orexin Proteins 0.000 description 7
- NVXVWITUGLSHCU-UHFFFAOYSA-N 2-methylquinoline-4-carbothioic s-acid Chemical compound C1=CC=CC2=NC(C)=CC(C(S)=O)=C21 NVXVWITUGLSHCU-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 208000004454 Hyperalgesia Diseases 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
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- OFNHNCAUVYOTPM-IIIOAANCSA-N orexin-a Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@H](C(N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N2)[C@@H](C)O)=O)CSSC1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CNC=N1 OFNHNCAUVYOTPM-IIIOAANCSA-N 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- IBSBXSPGFHPAIU-UHFFFAOYSA-N 8-bromo-2-methylquinoline-4-carboxylic acid Chemical compound C1=CC=C(Br)C2=NC(C)=CC(C(O)=O)=C21 IBSBXSPGFHPAIU-UHFFFAOYSA-N 0.000 description 5
- JNKCJGCFXQNMTM-UHFFFAOYSA-N 8-ethyl-2-methylquinoline-4-carboxylic acid Chemical compound C1=C(C)N=C2C(CC)=CC=CC2=C1C(O)=O JNKCJGCFXQNMTM-UHFFFAOYSA-N 0.000 description 5
- AVSYBDSWBTYMMZ-UHFFFAOYSA-N 8-fluoro-2-methoxyquinoline-4-carboxylic acid Chemical compound C1=CC=C(F)C2=NC(OC)=CC(C(O)=O)=C21 AVSYBDSWBTYMMZ-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 239000006196 drop Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 5
- 229960003081 probenecid Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229940044551 receptor antagonist Drugs 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
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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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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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
- A61P25/20—Hypnotics; Sedatives
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- 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
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
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| GB9903266 | 1999-02-12 | ||
| GBGB9903266.6A GB9903266D0 (en) | 1999-02-12 | 1999-02-12 | Compounds |
| GB9926430 | 1999-11-08 | ||
| GBGB9926430.1A GB9926430D0 (en) | 1999-11-08 | 1999-11-08 | Compounds |
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| ES2226785T3 true ES2226785T3 (es) | 2005-04-01 |
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| ES00906324T Expired - Lifetime ES2226785T3 (es) | 1999-02-12 | 2000-02-10 | Derivados de fenilurea como antagonistas de los receptores de orexina. |
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| Country | Link |
|---|---|
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| EP (1) | EP1150977B1 (enExample) |
| JP (1) | JP2002536445A (enExample) |
| AT (1) | ATE274512T1 (enExample) |
| AU (1) | AU2804400A (enExample) |
| DE (1) | DE60013250T2 (enExample) |
| ES (1) | ES2226785T3 (enExample) |
| WO (1) | WO2000047577A1 (enExample) |
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| US7517880B2 (en) | 1997-12-22 | 2009-04-14 | Bayer Pharmaceuticals Corporation | Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas |
| US7329670B1 (en) | 1997-12-22 | 2008-02-12 | Bayer Pharmaceuticals Corporation | Inhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas |
| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| US7928239B2 (en) * | 1999-01-13 | 2011-04-19 | Bayer Healthcare Llc | Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas |
| US7351834B1 (en) | 1999-01-13 | 2008-04-01 | Bayer Pharmaceuticals Corporation | ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| ATE538794T1 (de) | 1999-01-13 | 2012-01-15 | Bayer Healthcare Llc | Gamma carboxyarylsubstituierte diphenylharnstoffverbindungen als p38 kinasehemmer |
| WO2000042012A1 (en) | 1999-01-13 | 2000-07-20 | Bayer Corporation | φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS |
| JP2001106673A (ja) * | 1999-07-26 | 2001-04-17 | Banyu Pharmaceut Co Ltd | ビアリールウレア誘導体 |
| DE60024631T2 (de) * | 1999-07-26 | 2006-06-14 | Banyu Pharma Co Ltd | Biaryl-harnstoff-derivate |
| CA2423733A1 (en) * | 2000-08-31 | 2003-02-14 | Terukage Hirata | Novel propenohydroxamic acid derivatives |
| AU2002224885A1 (en) * | 2000-11-28 | 2002-06-11 | Smithkline Beecham Plc | Morpholine derivatives as antagonists of orexin receptors |
| US7371763B2 (en) | 2001-04-20 | 2008-05-13 | Bayer Pharmaceuticals Corporation | Inhibition of raf kinase using quinolyl, isoquinolyl or pyridyl ureas |
| DE60218445T2 (de) * | 2001-04-20 | 2007-11-29 | Bayer Pharmaceuticals Corp., West Haven | Inhibierung der raf-kinase durch chinolin-, isochinolin- oder pyridin-harnstoffe |
| ES2299567T3 (es) | 2001-05-05 | 2008-06-01 | Smithkline Beecham Plc | N-aroilaminas ciclicas. |
| WO2003029199A1 (en) * | 2001-09-28 | 2003-04-10 | Takeda Chemical Industries, Ltd. | Benzene derivatives, process for preparing the same and use thereof |
| GB0130341D0 (en) | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| MXPA04007832A (es) | 2002-02-11 | 2005-09-08 | Bayer Pharmaceuticals Corp | Aril-ureas con actividad inhibitoria de angiogenesis. |
| ATE529406T1 (de) | 2002-02-11 | 2011-11-15 | Bayer Healthcare Llc | Aryl-harnstoffe als kinase inhibitoren |
| NZ538029A (en) | 2002-07-09 | 2006-08-31 | Actelion Pharmaceuticals Ltd | 7,8,9,10-tetrahydro-6H-azepino, 6,7,8,9-tetrahydro-pyrido and 2,3-dihydro-2H-pyrrolo[2,1-b]-quinazolinone derivatives |
| KR20050043967A (ko) * | 2002-09-17 | 2005-05-11 | 액테리온 파마슈티칼 리미티드 | 1-피리딘-4-일-요소 유도체 |
| KR20050043988A (ko) | 2002-10-11 | 2005-05-11 | 액테리온 파마슈티칼 리미티드 | 설포닐아미노-아세트산 유도체 및 오렉신 수용체길항제로서 이들의 용도 |
| GB0225944D0 (en) * | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| BRPI0408815A (pt) * | 2003-03-28 | 2006-04-04 | Pharmacia & Upjohn Co Llc | moduladores alostéricos positivos do receptor nicotìnico da acetilcolina |
| US7538109B2 (en) | 2003-04-28 | 2009-05-26 | Actelion Pharmaceuticals Ltd | Quinoxalin-3-one derivatives as orexin receptor antagonists |
| EP1636585B2 (en) | 2003-05-20 | 2012-06-13 | Bayer HealthCare LLC | Diaryl ureas with kinase inhibiting activity |
| HRP20060073B1 (hr) | 2003-07-23 | 2014-03-14 | Bayer Healthcare Llc | Fluoro supstituirana omega-karboksiaril difenil urea za lijeäśenje i prevenciju bolesti i stanja |
| US7763638B2 (en) | 2004-03-01 | 2010-07-27 | Actelion Pharmaceuticals Ltd. | Substituted 1,2,3,4-tetrahydroisoquinoline derivatives |
| US20060178307A1 (en) * | 2005-01-26 | 2006-08-10 | The Regents Of The University Of California | Modulation of NMDA receptor currents via orexin receptor and/or CRF receptor |
| US7501395B2 (en) | 2005-04-25 | 2009-03-10 | Eisai R & D Management Co., Ltd. | Method of screening for antianxiety drugs |
| WO2007024754A1 (en) * | 2005-08-22 | 2007-03-01 | Amgen Inc. | Bis-aryl urea compounds for the treatment of protein kinase-mediated diseaes |
| FR2896799B1 (fr) * | 2006-02-02 | 2008-03-28 | Sanofi Aventis Sa | Derives de sulfonamides, leur preparation et leur application en therapeutique |
| WO2008008517A2 (en) | 2006-07-14 | 2008-01-17 | Merck & Co., Inc. | Bridged diazepan orexin receptor antagonists |
| PE20081229A1 (es) | 2006-12-01 | 2008-08-28 | Merck & Co Inc | Antagonistas de receptor de orexina de diazepam sustituido |
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| MX2010011663A (es) * | 2008-04-24 | 2011-01-21 | Abbott Gmbh & Co Kg | Derivados de 1-(7-hexahidropirrolo [3,4-c] pirrol-2 (1h)-il) quinolin-3-il)-(pirazin-2-il) urea y compuestos relacionados como glicogeno sintasa quinasa 3 (gsk-3). |
| EP2161266A1 (en) | 2008-08-22 | 2010-03-10 | EVOTEC Neurosciences GmbH | Benzofuran derivatives as orexin receptor antagonists |
| AR074426A1 (es) | 2008-12-02 | 2011-01-19 | Glaxo Group Ltd | Compuesto de n-(((1s,4s,6s)-3-(2-piridinilcarbonil)3-azabiciclo (4,1.0)hept-4-il) metil)-2-heteroarilamina, su uso para la prepracion de un medicamento para el tratamiento de una enfermedad que requiere un antagonista de un receptor de orexina humana y composicion farmaceutica que lo comprende |
| US20120040991A1 (en) | 2009-04-24 | 2012-02-16 | Glaxo Group Limited | 3-azabicyclo [4.1.0] heptanes used as orexin antagonists |
| EP2470523A1 (en) | 2009-08-24 | 2012-07-04 | Glaxo Group Limited | 5-methyl-piperidine derivatives as orexin receptor antagonists for the treatment of sleep disorder |
| WO2011023585A1 (en) | 2009-08-24 | 2011-03-03 | Glaxo Group Limited | Piperidine derivatives used as orexin antagonists |
| WO2011138265A2 (en) | 2010-05-03 | 2011-11-10 | Evotec Ag | Indole and indazole derivatives as orexin receptor antagonists |
| WO2011138266A1 (en) | 2010-05-03 | 2011-11-10 | Evotec Ag | Indolizine and imidazopyridine derivatives as orexin receptor antagonists |
| WO2012089607A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Novel compounds with a 3a-azabicyclo [4.1.0] heptane core acting on orexin receptors |
| WO2012089606A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Azabicyclo [4.1.0] hept - 4 - yl derivatives as human orexin receptor antagonists |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| NZ628491A (en) | 2012-02-07 | 2016-06-24 | Eolas Therapeutics Inc | Substituted prolines / piperidines as orexin receptor antagonists |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| US20160250224A1 (en) * | 2013-09-24 | 2016-09-01 | The Board Of Regents Of The University Of Texas System | Orexin-control of bone formation and loss |
| CA2934391A1 (en) * | 2013-12-20 | 2015-06-25 | Bayer Pharma Aktiengesellschaft | Glucose transport inhibitors |
| JP6663909B2 (ja) | 2014-08-13 | 2020-03-13 | エオラス セラピューティクス， インコーポレイテッド | オレキシンレセプターモジュレーターとしてのジフルオロピロリジン |
| WO2016075134A1 (en) * | 2014-11-12 | 2016-05-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of cancer |
| SI3414241T1 (sl) | 2016-02-12 | 2022-10-28 | Astrazeneca Ab | Halo-substituitani piperidini kot modulatorji receptorja oreksina |
| US20190151304A1 (en) | 2016-05-10 | 2019-05-23 | Inserm (Institut National De La Santé Et De La Rechercjae Médicale | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory |
| JP2022536755A (ja) * | 2019-06-14 | 2022-08-18 | アイエフエム デュー インコーポレイテッド | Ｓｔｉｎｇ活性に関連する状態を治療するための化合物および組成物 |
| CN117529475A (zh) | 2021-01-08 | 2024-02-06 | 艾福姆德尤股份有限公司 | 用于治疗与sting活性有关的疾病的含脲或类似物的杂双环化合物及其化合物 |
| CN114656406B (zh) * | 2022-01-25 | 2023-09-05 | 阿里生物新材料（常州）有限公司 | 一种2-氟代嘧啶-4-羧酸的合成方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| GB9302275D0 (en) * | 1993-02-05 | 1993-03-24 | Smithkline Beecham Plc | Novel compounds |
| US5552411A (en) | 1995-05-26 | 1996-09-03 | Warner-Lambert Company | Sulfonylquinolines as central nervous system and cardiovascular agents |
| ZA96497B (en) * | 1996-01-23 | 1996-08-13 | Bnfl Fluorchem Ltd | Halogenated compounds |
| TW477787B (en) | 1996-08-27 | 2002-03-01 | Pfizer | Pyrido six-membered nitrogen-containing cyclic ring derivatives having corticotropin releasing factor antagonist activity and pharmaceutical composition containing same |
| WO1998058905A1 (en) | 1997-06-25 | 1998-12-30 | Yamanouchi Pharmaceutical Co., Ltd. | Novel amidrazone derivatives having antifungal activity |
| AR016817A1 (es) * | 1997-08-14 | 2001-08-01 | Smithkline Beecham Plc | Derivados de fenilurea o feniltiourea, procedimiento para su preparacion, coleccion de compuestos, compuestos intermediarios, composicion farmaceutica,metodo de tratamiento y uso de dichos compuestos para la manufactura de un medicamento |
| US6083944A (en) | 1997-10-07 | 2000-07-04 | Cephalon, Inc. | Quinoline-containing α-ketoamide cysteine and serine protease inhibitors |
| WO1999038846A1 (en) | 1998-01-30 | 1999-08-05 | Procept, Inc. | Immunosuppressive agents |
-
2000
- 2000-02-10 AU AU28044/00A patent/AU2804400A/en not_active Abandoned
- 2000-02-10 AT AT00906324T patent/ATE274512T1/de not_active IP Right Cessation
- 2000-02-10 DE DE60013250T patent/DE60013250T2/de not_active Expired - Fee Related
- 2000-02-10 EP EP00906324A patent/EP1150977B1/en not_active Expired - Lifetime
- 2000-02-10 WO PCT/EP2000/001150 patent/WO2000047577A1/en not_active Ceased
- 2000-02-10 JP JP2000598497A patent/JP2002536445A/ja not_active Withdrawn
- 2000-02-10 ES ES00906324T patent/ES2226785T3/es not_active Expired - Lifetime
- 2000-02-10 US US09/913,236 patent/US6699879B1/en not_active Expired - Fee Related
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|---|---|
| EP1150977A1 (en) | 2001-11-07 |
| AU2804400A (en) | 2000-08-29 |
| WO2000047577A1 (en) | 2000-08-17 |
| DE60013250D1 (en) | 2004-09-30 |
| JP2002536445A (ja) | 2002-10-29 |
| ATE274512T1 (de) | 2004-09-15 |
| US6699879B1 (en) | 2004-03-02 |
| DE60013250T2 (de) | 2005-09-08 |
| EP1150977B1 (en) | 2004-08-25 |
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