JP2008542367A5 - - Google Patents
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- JP2008542367A5 JP2008542367A5 JP2008514588A JP2008514588A JP2008542367A5 JP 2008542367 A5 JP2008542367 A5 JP 2008542367A5 JP 2008514588 A JP2008514588 A JP 2008514588A JP 2008514588 A JP2008514588 A JP 2008514588A JP 2008542367 A5 JP2008542367 A5 JP 2008542367A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- cyanomethyl
- phenyl
- carboxamide
- quinoline
- 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.)
- Pending
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- 150000001875 compounds Chemical class 0.000 claims description 104
- 239000011780 sodium chloride Substances 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 32
- 108010040716 Neurokinin-3 Receptors Proteins 0.000 claims description 31
- 102000002003 Neurokinin-3 Receptors Human genes 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- NPZTUJOABDZTLV-UHFFFAOYSA-N 1,2-dihydrobenzotriazol-4-one Chemical compound O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 13
- 208000008589 Obesity Diseases 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 12
- 235000020824 obesity Nutrition 0.000 claims description 12
- OZAIFHULBGXAKX-UHFFFAOYSA-N precursor Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 201000000980 schizophrenia Diseases 0.000 claims description 10
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- 239000003814 drug Substances 0.000 claims description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- -1 Bromomethyl-substituted quinoline ester Chemical class 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 229940113083 morpholine Drugs 0.000 claims description 6
- MNWBNISUBARLIT-UHFFFAOYSA-N Sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 150000002825 nitriles Chemical class 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- ZLQPXWZKRCEEHM-QHCPKHFHSA-N 3-(cyanomethyl)-2-(3-fluorophenyl)-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide Chemical compound N([C@@H](CC)C=1C=CC=CC=1)C(=O)C(C1=CC=CC=C1N=1)=C(CC#N)C=1C1=CC=CC(F)=C1 ZLQPXWZKRCEEHM-QHCPKHFHSA-N 0.000 claims description 3
- UOUOEFBZRSHKCK-SFHVURJKSA-N 3-(cyanomethyl)-2-phenyl-N-[(1S)-1-phenylethyl]quinoline-4-carboxamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)C(C1=CC=CC=C1N=1)=C(CC#N)C=1C1=CC=CC=C1 UOUOEFBZRSHKCK-SFHVURJKSA-N 0.000 claims description 3
- NGIJJOHATIDYHC-QHCPKHFHSA-N 3-(cyanomethyl)-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide Chemical compound N([C@@H](CC)C=1C=CC=CC=1)C(=O)C(C1=CC=CC=C1N=1)=C(CC#N)C=1C1=CC=CC=C1 NGIJJOHATIDYHC-QHCPKHFHSA-N 0.000 claims description 3
- HJPHSXDMFNIHNB-SANMLTNESA-N 3-(cyanomethyl)-N-[(S)-cyclopropyl-(3-fluorophenyl)methyl]-2-(3-fluorophenyl)quinoline-4-carboxamide Chemical compound FC1=CC=CC([C@@H](NC(=O)C=2C3=CC=CC=C3N=C(C=2CC#N)C=2C=C(F)C=CC=2)C2CC2)=C1 HJPHSXDMFNIHNB-SANMLTNESA-N 0.000 claims description 3
- OBXIJGKFCRSVFY-SANMLTNESA-N 3-(cyanomethyl)-N-[(S)-cyclopropyl-(3-fluorophenyl)methyl]-2-phenylquinoline-4-carboxamide Chemical compound FC1=CC=CC([C@@H](NC(=O)C=2C3=CC=CC=C3N=C(C=2CC#N)C=2C=CC=CC=2)C2CC2)=C1 OBXIJGKFCRSVFY-SANMLTNESA-N 0.000 claims description 3
- IPBVNPXQWQGGJP-UHFFFAOYSA-N Phenyl acetate Chemical compound CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 3
- UOUOEFBZRSHKCK-UHFFFAOYSA-N 3-(cyanomethyl)-2-phenyl-N-(1-phenylethyl)quinoline-4-carboxamide Chemical compound C=1C=CC=CC=1C(C)NC(=O)C(C1=CC=CC=C1N=1)=C(CC#N)C=1C1=CC=CC=C1 UOUOEFBZRSHKCK-UHFFFAOYSA-N 0.000 claims description 2
- NGIJJOHATIDYHC-UHFFFAOYSA-N 3-(cyanomethyl)-2-phenyl-N-(1-phenylpropyl)quinoline-4-carboxamide Chemical compound C=1C=CC=CC=1C(CC)NC(=O)C(C1=CC=CC=C1N=1)=C(CC#N)C=1C1=CC=CC=C1 NGIJJOHATIDYHC-UHFFFAOYSA-N 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 210000004027 cells Anatomy 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
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- 239000007787 solid Substances 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 229910052722 tritium Inorganic materials 0.000 description 9
- YZCKVEUIGOORGS-NJFSPNSNSA-N tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 9
- MVPKZCSALOEDLD-UHFFFAOYSA-N 3-(cyanomethyl)-2-phenylquinoline-4-carboxylic acid Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=C(CC#N)C=1C1=CC=CC=C1 MVPKZCSALOEDLD-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 238000004166 bioassay Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 210000003169 Central Nervous System Anatomy 0.000 description 6
- 102000014961 Protein Precursors Human genes 0.000 description 6
- 108010078762 Protein Precursors Proteins 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 239000002609 media Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- FAUQTKMKTGDFKE-UHFFFAOYSA-N methyl 3-(cyanomethyl)-2-phenylquinoline-4-carboxylate Chemical compound N=1C2=CC=CC=C2C(C(=O)OC)=C(CC#N)C=1C1=CC=CC=C1 FAUQTKMKTGDFKE-UHFFFAOYSA-N 0.000 description 6
- 230000002829 reduced Effects 0.000 description 6
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- WJCDZNCXXWHQFR-UHFFFAOYSA-N 3-(cyanomethyl)-2-(3-fluorophenyl)quinoline-4-carboxylic acid Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=C(CC#N)C=1C1=CC=CC(F)=C1 WJCDZNCXXWHQFR-UHFFFAOYSA-N 0.000 description 4
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- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 4
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N HEPES Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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0.95ããªã¢ã«)ã®THF(10ml)溶液ã«æ°Žé žåãªããŠã äžæ°Žåç©(46mg, 1.9ããªã¢ã«)ã®æ°Ž(ïŒml)溶液ãå ãããåå¿æ··åç©ãRTã§12hæªæãããæ®çç©ãïŒïŒ ã¯ãšã³é žã§é žæ§åããé ¢é žãšãã«(50mlÃïŒ)ã§æœåºãããææ©çžãåé¢ãããã©ã€ã³(20ml)ã§æŽãããããŠç¡«é žã
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3â(ããã¢ã¡ãã«)â2âãã§ãã«ãããªã³â4ã«ã«ããã·ã¬ãŒã(1a) (356mg, 1.0ããªã¢ã«)ã®DMF(10mL)溶液ã«ã·ã¢ã³åãããªãŠã (54mg, 1.1 ããªã¢ã«)ãå ããåå¿æ··åç©ãRTã§12ïœæªæãããå šæº¶åªãæžå§äžã§é€å»ããæ®çç©ãé ¢é žãšãã«ãš10ïŒ éçé žãããªãŠã 氎溶液ã®éã§åé ããç¡«é žãããªãŠã ã§ä¹Ÿç¥ãã次ã«æžå§äžã§æ¿çž®ãããæ®çç©ãã¯ãããã°ã©ãã£ãŒã«ãã10â15ïŒ é ¢é žãšãã«ïŒãããµã³ã§æº¶é¢ããŠç²Ÿè£œããŠãæšé¡ã®ååç©(287mg, 95ïŒ )ããªããã¯ã€ãè²ã®åºäœãšããŠåŸãã1H NMR (300MHz, CDCl3) ÎŽ 4.01 (s, 3H), 4.65 (s, 2H), 7.37 (m, 1H), 7.78 (m, 2H), 7.79 (m, 1H), 8.10 (m, 1H), 8.30 (m, 1H), 8.37 (m, 2H), 8.54 (m, 1H)ãMS APCI, m/z = 303 (M+1)ã LCMS: 2.12 minã
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0.95ããªã¢ã«)ã®THF(10ml)溶液ã«æ°Žé žåãªããŠã äžæ°Žåç©(46mg, 1.9ããªã¢ã«)ã®æ°Ž(ïŒml)溶液ãå ãããåå¿æ··åç©ãRTã§12hæªæãããæ®çç©ãïŒïŒ ã¯ãšã³é žã§é žæ§åããé ¢é žãšãã«(50mlÃïŒ)ã§æœåºãããææ©çžãåé¢ãããã©ã€ã³(20ml)ã§æŽãããããŠç¡«é žã
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ã¹ããŒã ïŒã«ç€ºããåå¿ã«ãããæšé¡ã®ååç©(ïŒ)ãçœè²åºäœ(40mg, 46ïŒ
)ãšããŠåŸãã1H NMR (300MHz, CDCl3) ÎŽ 3.78 (s, 3H), 3.83 (s, 2H), 5.87 (d, 1H), 6.72 (d, 1H), 6.74 (d, 2H), 7.04 (d, 2H), 7.06 (m, 1H), 7.37 (m, 2H), 7.41 (m, 2H), 7.76(m, 1H), 7.84 (m, 2H), 8.04â8.19 (m, 2H)ãMS APCI, m/z = 436 (M+1)ãLCMS: 2.20 minã
å®æœäŸïŒïŒ3â(ã·ã¢ãã¡ãã«)âNâ[(S)âã·ã¯ããããã«(3âãã«ãªããã§ãã«)ã¡ãã«]â2âãã§ãã«ãããªã³â4âã«ã«ãããµãã
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ã¹ããŒã ïŒã«ç€ºããåå¿ã«ãããæšé¡ã®ååç©(ïŒ)ãçœè²åºäœ(39.2mg, 45ïŒ
)ãšããŠåŸãã1H NMR (300MHz, CDCl3) ÎŽ 0.52 (m, 2H), 0.70 (m, 2H), 1.60 (m, 1H), 4.67 (s,
2H), 5.03 (d, 1H), 6.86 (m, 1H), 6.94 (d, 1H), 7.16 (m, 1H), 7.24 (m, 1H), 7.30
(m, 1H), 7.39 (m, 1H), 7.76 (m, 2H), 7.84 (m, 2H), 8.04â8.19 (m, 4H)ãMS APCI,
m/z = 436 (M+1)ãLCMS: 2.37 minã
2H), 5.03 (d, 1H), 6.86 (m, 1H), 6.94 (d, 1H), 7.16 (m, 1H), 7.24 (m, 1H), 7.30
(m, 1H), 7.39 (m, 1H), 7.76 (m, 2H), 7.84 (m, 2H), 8.04â8.19 (m, 4H)ãMS APCI,
m/z = 436 (M+1)ãLCMS: 2.37 minã
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ž(61.2mg, 0.2ããªã¢ã«)ã䜿çšãã以å€ã¯å®æœäŸïŒã«èšèŒããæé ãšåæ§ã®æé ãçšããŠè£œé ããã
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ã»ãã¿ãŒèªçºã«ã«ã·ãŠã åå¡ãå®éããããã«ã现èããŸããã³ã¯ã¹ã®å¹³è¡¡å¡©é¡æº¶æ¶²ãHEPES 15mMãåã³ããããã·ã2.5mMãpH 7.4ããæãæ€å®ãããã¡ã§æŽã£ãã次ã«çŽ°èã«æ€å®ãããã¡äžFluo4ïŒAMè²çŽ (4.4ÎŒM)ãããŒãã£ã³ã°ããã现èãïŒæéã€ã³ãã¥ããŒããã次ã«æ€å®ãããã¡ã§æŽããã»ã³ã¯ããïŒsenktideïŒ0.02â300nMã«æé²ãããããŠèå å¿çããFLIPRæ©åš(ã¢ã¬ãã¥ã©ãŒããã€ã¹ç€Ÿ)ãçšããŠèšé²ãããã¢ãŽãã¹ãå¿çã®æ®æäœçšãå®éããããã«ã现èããè©Šéšååç©ã®æ¿åºŠãå€ããŠïŒã20åéäºåå¹é€ãã次ã«ãåç¬ã§çŽ70ïŒ ã®æ倧ã«ã«ã·ãŠã å¿çãåŒãåºãæ¿åºŠã§ããïŒnMã®ã»ã³ã¯ããã«æé²ãããåŸãããããŒã¿ãXLfitãœãããŠã§ã¢(IDBS補é è )ãçšããŠåæããŠãEC50å€åã³IC50å€ã決å®ããã
Claims (9)
- åŒïŒ©ïŒ
åŒäžã
1ã¯ïŒšã1-6ã¢ã«ãã«âã3-6ã·ã¯ãã¢ã«ãã«âã1-6ã¢ã«ãã«âïŒïŒ¯ïŒâåã³ïŒ£1-4ã¢ã«ãã«ïŒ¯ïŒ£ïŒïŒ¯ïŒâããéžã°ãïŒ
ã¯ãã§ãã«åã¯ïŒ£3-7ã·ã¯ãã¢ã«ãã«âã§ããïŒ
ïœã¯ïŒãïŒåã¯ïŒã§ããïŒ
2ã¯ããããç¬ç«ããŠïŒšãâãâ2ãâãããã²ã³ã1-6ã¢ã«ãã«âã3-7ã·ã¯ãã¢ã«ãã«âã1-6ã¢ã«ã³ãã·âåã³ïŒ£1-6ã¢ã«ã³ãã·ïŒ£1-6ã¢ã«ãã«âããéžã°ãïŒ
3ã¯ããããç¬ç«ããŠïŒšãâãâ2ãâ2ãâãããã²ã³ã1-6ã¢ã«ãã«âã1-6ã¢ã«ã³ãã·âåã³ïŒ£1-6ã¢ã«ã³ãã·ïŒ£1-6ã¢ã«ãã«âããéžã°ãïŒ
ïœã¯ïŒãïŒåã¯ïŒã§ããïŒ
5ã¯ããããç¬ç«ããŠïŒšãâãâãããã²ã³ãâ6ãâ6ãâ67ãâ6ãâ6åã³â26ããéžã°ãïŒ
ïœã¯ïŒãïŒåã¯ïŒã§ããïŒ
ããã§ã
6åã³ïŒ²7ã¯ããããç¬ç«ããŠïŒšãçŽéåã¯åå²éã®ïŒ£1-6ã¢ã«ãã«åºãçŽéåã¯åå²éã®ïŒ£2-6ã¢ã«ã±ãã«åã¯ã¢ã«ããã«åºãåã³ïŒãïŒåã¯ïŒåã®äºéåã¯äžéçµåãæãã3-7ççŽ ç°åŒåºããéžã°ããããã§ããããã®åºã¯é眮æã§ããããåã¯âãïŒïŒ¯ãâ2ãâãããã²ã³ãã¢ãªãŒã«åã³ïŒ£1-3ã¢ã«ã³ãã·âããéžã°ããïŒåè¥ããã¯ãã以äžã®åºã§çœ®æãããŠããïŒ
ãããŠã
1ã2åã¯ïŒ²3ãã¢ã«ãã«ãã·ã¯ãã¢ã«ãã«ãã¢ã«ã³ãã·åã¯ã¢ã«ã³ãã·ã¢ã«ãã«åºã§ããå Žåã該åºã¯é眮æã§ããããåã¯ãããããç¬ç«ããŠâãâ2ãâããã§ãã«åã³ããã²ã³ããéžã°ããïŒãïŒãïŒãïŒè¥ããã¯ïŒåã®çœ®æåºãæããã - ã¯ãã§ãã«ã§ããïŒ
1ã¯ïŒ£1-6ã¢ã«ãã«âã3-6ã·ã¯ãã¢ã«ãã«âãåã¯ïŒ£1-6ã¢ã«ãã«ââïŒïŒ¯ïŒâããéžã°ãïŒ
ïœã¯ããããç¬ç«ããŠïŒåã¯ïŒããéžã°ããã
è«æ±é ïŒèšèŒã®ååç©ãåã¯ãã®ç«äœç°æ§äœããšãã³ããªããŒãçäœå ã§å æ°Žå解å¯èœãªåé§äœãè¥ããã¯è¬åŠç蚱容塩ã - ã¯ãã§ãã«ã§ããïŒ
1ã¯ïŒ£1-6ã¢ã«ãã«åã¯âïŒïŒ£ïŒ¯ïŒââ1-6ã¢ã«ãã«ããéžã°ãïŒ
ïœã¯ããããïŒã§ããã
è«æ±é ïŒèšèŒã®ååç©ãåã¯ãã®ç«äœç°æ§äœããšãã³ããªããŒãçäœå ã§å æ°Žå解å¯èœãªåé§äœãè¥ããã¯è¬åŠç蚱容塩ã - 3â(ã·ã¢ãã¡ãã«)â2âãã§ãã«âNâ[(1S)â1âãã§ãã«ãããã«]ãããªã³â4âã«ã«ãããµãã;
3â(ã·ã¢ãã¡ãã«)â2âãã§ãã«âNâ[(1S)â1âãã§ãã«ãšãã«]ãããªã³â4âã«ã«ãããµãã;
ã¡ãã«(2R)â(ïœ[3â(ã·ã¢ãã¡ãã«)â2âãã§ãã«ãããªã³â4âã€ã«]ã«ã«ããã«ïœã¢ãã)(ãã§ãã«)ã¢ã»ããŒã;
3â(ã·ã¢ãã¡ãã«)âNâ[(S)âã·ã¯ããããã«(3âãã«ãªããã§ãã«)ã¡ãã«]â2âãã§ãã«ãããªã³â4âã«ã«ãããµãã;
3â(ã·ã¢ãã¡ãã«)â2â(3âãã«ãªããã§ãã«)âNâ[(1S)â1âãã§ãã«ãããã«]ãããªã³â4âã«ã«ãããµããã
3â(ã·ã¢ãã¡ãã«)âNâ[(S)âã·ã¯ããããã«(3âãã«ãªããã§ãã«)ã¡ãã«]â2â(3âãã«ãªããã§ãã«)ãããªã³â4âã«ã«ãããµãã;
ã¡ãã«2â(3â(ã·ã¢ãã¡ãã«)â2âãã§ãã«ãããªã³â4âã«ã«ãããµãã)â2âãã§ãã«ã¢ã»ããŒã;
3â(ã·ã¢ãã¡ãã«)â2âãã§ãã«âNâ(1âãã§ãã«ãšãã«)ãããªã³â4âã«ã«ãããµããïŒåã³
3â(ã·ã¢ãã¡ãã«)â2âãã§ãã«âNâ(1âãã§ãã«ãããã«)ãããªã³â4âã«ã«ãããµãã;
ããéžã°ãããè«æ±é ïŒèšèŒã®ååç©ãåã¯ãã®ç«äœç°æ§äœããšãã³ããªããŒãçäœå ã§å æ°Žå解å¯èœãªåé§äœãè¥ããã¯è¬åŠç蚱容塩ã - é žïŒ
- ããã¢ã¡ãã«çœ®æãããªã³ãšã¹ãã«ïŒ
è©²é žãšã¢ãã³ïŒ
- è¬åŠçã«èš±å®¹ãããåžéå€ãæ»æ²¢å€åã¯æ äœãšè«æ±é ïŒèšèŒã®ååç©ãåã¯ãã®ç«äœç°æ§äœããšãã³ããªããŒãçäœå ã§å æ°Žå解å¯èœãªåé§äœãè¥ããã¯è¬åŠç蚱容塩ãšãå«ãå»è¬çµæç©ã
- âïŒã¬ã»ãã¿ãŒã®èª¿ç¯ãæçãªçŸæ£åã¯èº«äœç¶æ ãæ²»çåã¯äºé²ããããã®å»è¬ã®è£œé ã«ããããè«æ±é ïŒèšèŒã®ååç©ãåã¯ãã®ç«äœç°æ§äœããšãã³ããªããŒãçäœå ã§å æ°Žå解å¯èœãªåé§äœãè¥ããã¯è¬åŠç蚱容塩ã®äœ¿çšã
- çŸæ£åã¯èº«äœç¶æ ãäžå®ããã€ç ãçµ±å倱調çåã³è¥æºããéžã°ãããè«æ±é ïŒã«èšèŒã®äœ¿çšã
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US68741805P | 2005-06-03 | 2005-06-03 | |
PCT/SE2006/000630 WO2006130080A2 (en) | 2005-06-03 | 2006-05-30 | Quinoline derivatives as nk3 anatgonists |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008542367A JP2008542367A (ja) | 2008-11-27 |
JP2008542367A5 true JP2008542367A5 (ja) | 2009-07-16 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2008514588A Pending JP2008542367A (ja) | 2005-06-03 | 2006-05-30 | ïœâïŒã¢ã³ã¿ãŽãã¹ããšããŠã®ãããªã³èªå°äœ |
Country Status (11)
Country | Link |
---|---|
US (1) | US20080200500A1 (ja) |
EP (1) | EP1891012A2 (ja) |
JP (1) | JP2008542367A (ja) |
KR (1) | KR20080016591A (ja) |
CN (1) | CN101189211A (ja) |
AU (1) | AU2006253054A1 (ja) |
CA (1) | CA2611060A1 (ja) |
IL (1) | IL187410A0 (ja) |
MX (1) | MX2007014831A (ja) |
NO (1) | NO20080033L (ja) |
WO (1) | WO2006130080A2 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
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US8173639B2 (en) | 2007-04-26 | 2012-05-08 | H. Lundbeck A/S | Isoquinolinone derivatives as NK3 antagonists |
WO2008131779A1 (en) | 2007-04-26 | 2008-11-06 | H. Lundbeck A/S | Isoquinolinone derivatives as nk3 antagonists |
KR20110026429A (ko) | 2008-06-23 | 2011-03-15 | í. 룬ë벡 ìí¬í°ìì ì€ì¹Žëž | ïœ3 êžžíì ë¡ìì ìŽìíŽëëŠ¬ë Œ ì ë첎 |
US8242134B2 (en) | 2008-09-15 | 2012-08-14 | H. Lundbeck A/S | Isoquinolinone derivatives as NK3 antagonists |
AR073891A1 (es) | 2008-10-20 | 2010-12-09 | Lundbeck & Co As H | Derivados de isoquinolinona antagonistas de receptores nk3, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento de psicosis, alzheimer y otras enfermedades. |
TW201143768A (en) | 2009-12-15 | 2011-12-16 | Lundbeck & Co As H | Pyridone derivatives as NK3 antagonists |
TW201144311A (en) | 2010-03-12 | 2011-12-16 | Lundbeck & Co As H | Azaisoquionolinone derivatives as NK3 antagonists |
EP3915560A1 (en) | 2014-06-25 | 2021-12-01 | Emory University | Methods of managing conditioned fear with neurokinin receptor antagonists |
KR20160069683A (ko) | 2014-12-09 | 2016-06-17 | ë°±ì°¬ì± | 윀ë¹ë³Žíž ë° ê·ž ì ì ë°©ë² |
EP3704271A4 (en) | 2017-11-02 | 2021-09-08 | California Institute of Technology | NEUROKININ ANTAGONISTS AND RELATED USES |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
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HU226535B1 (en) * | 1994-05-27 | 2009-03-30 | Glaxosmithkline Spa | Quinoline derivatives as tachykinin nk3 receptor antagonists, pharmaceutical compositions containing them, and their use |
IT1270615B (it) * | 1994-07-14 | 1997-05-07 | Smithkline Beecham Farma | Uso di derivati di chinolina |
GB9524137D0 (en) * | 1995-11-24 | 1996-01-24 | Smithkline Beecham Spa | Novel compounds |
AR004735A1 (es) * | 1995-11-24 | 1999-03-10 | Smithkline Beecham Spa | Quinoleina 4-amido sustituida, un procedimiento para su preparacion, una composicion farmaceutica que los contiene y el uso de los mismos para lapreparacion de un medicamento. |
ATE244711T1 (de) * | 1997-05-23 | 2003-07-15 | Glaxosmithkline Spa | Chinolin-4-carboxamidderivate als nk-2 und nk-3 rezeptor antagonisten |
AP1201A (en) * | 1997-09-17 | 2003-09-01 | Smithkline Beecham Corp | Method for the synthesis of quinoline derivatives. |
CN1406225A (zh) * | 1998-11-20 | 2003-03-26 | èå °çŽ å²å¯äžå è±æ©æéå ¬åž | çšäœnkïŒ3ånkïŒ2åäœæ®æåçå¹åïŒ4ïŒç²é °èºè¡çç© |
JP2004525183A (ja) * | 2001-04-11 | 2004-08-19 | ã°ã©ã¯ãœã¹ãã¹ã¯ã©ã€ã³ã»ãœã·ãšã¿ã»ãã«ã»ã¢ããªã | ïœâïŒããã³ïœïœâïŒå容äœã¢ã³ã¿ãŽãã¹ããšããŠã®ãããªã³âïŒâã«ã«ãããµããèªå°äœ |
JP2009504642A (ja) * | 2005-08-11 | 2009-02-05 | ã¢ã¹ãã©ãŒãã«ã»ã¢ã¯ããšãã©ãŒã° | ïœâïŒå容äœã®èª¿ç¯å€ãšããŠã®ãªããœããªãžã«ãããªã³ã¢ãã |
AR058051A1 (es) * | 2005-09-21 | 2008-01-23 | Astrazeneca Ab | Quinolinas de alquilnitrilo.proceso de obtencion y composiciones farmaceuticas. |
EP1981882A4 (en) * | 2006-01-27 | 2009-11-18 | Astrazeneca Ab | QUINOLINES SUBSTITUTED BY AN AMIDE |
-
2006
- 2006-05-30 AU AU2006253054A patent/AU2006253054A1/en not_active Abandoned
- 2006-05-30 CA CA002611060A patent/CA2611060A1/en not_active Abandoned
- 2006-05-30 EP EP06747824A patent/EP1891012A2/en not_active Withdrawn
- 2006-05-30 CN CNA2006800196735A patent/CN101189211A/zh active Pending
- 2006-05-30 JP JP2008514588A patent/JP2008542367A/ja active Pending
- 2006-05-30 MX MX2007014831A patent/MX2007014831A/es not_active Application Discontinuation
- 2006-05-30 US US11/914,583 patent/US20080200500A1/en not_active Abandoned
- 2006-05-30 WO PCT/SE2006/000630 patent/WO2006130080A2/en active Application Filing
- 2006-05-30 KR KR1020077027965A patent/KR20080016591A/ko not_active Application Discontinuation
-
2007
- 2007-11-15 IL IL187410A patent/IL187410A0/en unknown
-
2008
- 2008-01-03 NO NO20080033A patent/NO20080033L/no unknown
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