JP2006508116A - Ltd4アンタゴニストとしての新規三環式誘導体 - Google Patents
Ltd4アンタゴニストとしての新規三環式誘導体 Download PDFInfo
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- JP2006508116A JP2006508116A JP2004550982A JP2004550982A JP2006508116A JP 2006508116 A JP2006508116 A JP 2006508116A JP 2004550982 A JP2004550982 A JP 2004550982A JP 2004550982 A JP2004550982 A JP 2004550982A JP 2006508116 A JP2006508116 A JP 2006508116A
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- Prior art keywords
- dihydro
- pyridin
- benzoxepino
- thio
- acid
- 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.)
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- 239000005557 antagonist Substances 0.000 title description 7
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 215
- 238000000034 method Methods 0.000 claims abstract description 52
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 208000026935 allergic disease Diseases 0.000 claims abstract description 9
- 230000002265 prevention Effects 0.000 claims abstract description 7
- -1 monoalkylamino Chemical group 0.000 claims description 168
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 66
- 125000001424 substituent group Chemical group 0.000 claims description 41
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 34
- 238000004519 manufacturing process Methods 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 20
- 235000019260 propionic acid Nutrition 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
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- 230000001575 pathological effect Effects 0.000 claims description 9
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- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 235000010233 benzoic acid Nutrition 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 206010027599 migraine Diseases 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
- 208000024780 Urticaria Diseases 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 230000006872 improvement Effects 0.000 claims description 7
- 125000004442 acylamino group Chemical group 0.000 claims description 6
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- 206010006448 Bronchiolitis Diseases 0.000 claims description 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 5
- 206010039094 Rhinitis perennial Diseases 0.000 claims description 5
- 208000002365 Viral Bronchiolitis Diseases 0.000 claims description 5
- 125000005120 alkyl cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- PNOCLWDEJRKWDF-UHFFFAOYSA-N 2-[[9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]acetic acid Chemical compound C1=C2C(SCC(=O)O)C3=CC=CN=C3COC2=CC=C1OCC1=CC=C(C=C(F)C(F)=C2)C2=N1 PNOCLWDEJRKWDF-UHFFFAOYSA-N 0.000 claims description 4
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 claims description 4
- OLKUFZKAFAHFAP-UHFFFAOYSA-N 3-[[9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]-3-methylbutanoic acid Chemical compound C1=C2C(SC(C)(CC(O)=O)C)C3=CC=CN=C3COC2=CC=C1OCC1=CC=C(C=C(F)C(F)=C2)C2=N1 OLKUFZKAFAHFAP-UHFFFAOYSA-N 0.000 claims description 4
- QPNKWUKRPUIIAQ-UHFFFAOYSA-N 3-[[9-[(7-chloro-6-fluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]propanoic acid Chemical compound C1=C2C(SCCC(=O)O)C3=CC=CN=C3COC2=CC=C1OCC1=CC=C(C=C(F)C(Cl)=C2)C2=N1 QPNKWUKRPUIIAQ-UHFFFAOYSA-N 0.000 claims description 4
- PMSGXRLYMCEJQU-ZZXKWVIFSA-N 9-[(e)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-11-[2-(2h-tetrazol-5-yl)ethylsulfanyl]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridine Chemical compound N1=C2C=C(F)C(F)=CC2=CC=C1\C=C\C(C=C12)=CC=C1OCC1=NC=CC=C1C2SCCC1=NN=NN1 PMSGXRLYMCEJQU-ZZXKWVIFSA-N 0.000 claims description 4
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 4
- 208000001640 Fibromyalgia Diseases 0.000 claims description 4
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- BPNOGBPLSZHUGE-UHFFFAOYSA-N 2-[1-[[9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanylmethyl]cyclopropyl]acetic acid Chemical compound C12=CC=CN=C2COC2=CC=C(OCC=3N=C4C=C(F)C(F)=CC4=CC=3)C=C2C1SCC1(CC(=O)O)CC1 BPNOGBPLSZHUGE-UHFFFAOYSA-N 0.000 claims description 3
- GYYISXLMDPGNDD-ZZXKWVIFSA-N 2-[1-[[9-[(e)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanylmethyl]cyclopropyl]acetic acid Chemical compound C12=CC=CN=C2COC2=CC=C(\C=C\C=3N=C4C=C(F)C(F)=CC4=CC=3)C=C2C1SCC1(CC(=O)O)CC1 GYYISXLMDPGNDD-ZZXKWVIFSA-N 0.000 claims description 3
- ROJDXFZAEPIOCC-UHFFFAOYSA-N 2-[[9-[(7-chloro-6-fluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]acetic acid Chemical compound C1=C2C(SCC(=O)O)C3=CC=CN=C3COC2=CC=C1OCC1=CC=C(C=C(F)C(Cl)=C2)C2=N1 ROJDXFZAEPIOCC-UHFFFAOYSA-N 0.000 claims description 3
- WUUCIVNJEOVHOV-UHFFFAOYSA-N 3-[[9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]propanoic acid Chemical compound C1=C2C(SCCC(=O)O)C3=CC=CN=C3COC2=CC=C1OCC1=CC=C(C=C(F)C(F)=C2)C2=N1 WUUCIVNJEOVHOV-UHFFFAOYSA-N 0.000 claims description 3
- WWUVRNPLHSRXHV-UHFFFAOYSA-N 3-[[9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[4,3-b]pyridin-11-yl]sulfanyl]propanoic acid Chemical compound O1CC2=CC=CN=C2C(SCCC(=O)O)C2=CC(OCC=3N=C4C=C(F)C(F)=CC4=CC=3)=CC=C21 WWUVRNPLHSRXHV-UHFFFAOYSA-N 0.000 claims description 3
- XBQBKXHXJXVKPN-ZZXKWVIFSA-N 3-[[9-[(e)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]propanoic acid Chemical compound O1CC2=NC=CC=C2C(SCCC(=O)O)C2=CC(\C=C\C=3N=C4C=C(F)C(F)=CC4=CC=3)=CC=C21 XBQBKXHXJXVKPN-ZZXKWVIFSA-N 0.000 claims description 3
- 208000005615 Interstitial Cystitis Diseases 0.000 claims description 3
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004948 alkyl aryl alkyl group Chemical group 0.000 claims description 3
- 230000000172 allergic effect Effects 0.000 claims description 3
- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 3
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- KBNWIWYCOPKHBC-UHFFFAOYSA-N 2-[1-[[9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[4,3-b]pyridin-11-yl]sulfanylmethyl]cyclopropyl]acetic acid Chemical compound C12=CC(OCC=3N=C4C=C(F)C(F)=CC4=CC=3)=CC=C2OCC2=CC=CN=C2C1SCC1(CC(=O)O)CC1 KBNWIWYCOPKHBC-UHFFFAOYSA-N 0.000 claims description 2
- ZMQFCIHNHAQNAQ-ZZXKWVIFSA-N 2-[[9-[(e)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]acetic acid Chemical compound O1CC2=NC=CC=C2C(SCC(=O)O)C2=CC(\C=C\C=3N=C4C=C(F)C(F)=CC4=CC=3)=CC=C21 ZMQFCIHNHAQNAQ-ZZXKWVIFSA-N 0.000 claims description 2
- MHABCZSIDVZHOQ-UHFFFAOYSA-N 3-[[9-[(6,7-difluoroquinolin-2-yl)methoxy]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridin-11-yl]sulfanyl]-2,2-dimethylpropanoic acid Chemical compound C1=C2C(SCC(C)(C)C(O)=O)C3=CC=CN=C3COC2=CC=C1OCC1=CC=C(C=C(F)C(F)=C2)C2=N1 MHABCZSIDVZHOQ-UHFFFAOYSA-N 0.000 claims description 2
- BCTLZWXWOKDEJF-ZZXKWVIFSA-N 3-[[9-[(e)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5,11-dihydro-[1]benzoxepino[4,3-b]pyridin-11-yl]sulfanyl]propanoic acid Chemical compound O1CC2=CC=CN=C2C(SCCC(=O)O)C2=CC(\C=C\C=3N=C4C=C(F)C(F)=CC4=CC=3)=CC=C21 BCTLZWXWOKDEJF-ZZXKWVIFSA-N 0.000 claims description 2
- IOUGOEHZTBRJIY-UHFFFAOYSA-N 9-[(6,7-difluoroquinolin-2-yl)methoxy]-11-[2-(2h-tetrazol-5-yl)ethylsulfanyl]-5,11-dihydro-[1]benzoxepino[3,4-b]pyridine Chemical compound N1=C2C=C(F)C(F)=CC2=CC=C1COC(C=C12)=CC=C1OCC1=NC=CC=C1C2SCCC1=NN=NN1 IOUGOEHZTBRJIY-UHFFFAOYSA-N 0.000 claims description 2
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 239000000938 histamine H1 antagonist Substances 0.000 claims description 2
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- 208000005577 Gastroenteritis Diseases 0.000 claims 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 242
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- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- IRUDOFZPRBTTQY-UHFFFAOYSA-N methyl 2,2-dimethyl-3-sulfanylpropanoate Chemical compound COC(=O)C(C)(C)CS IRUDOFZPRBTTQY-UHFFFAOYSA-N 0.000 description 1
- YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
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- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
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- 125000001624 naphthyl group Chemical group 0.000 description 1
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- 235000006408 oxalic acid Nutrition 0.000 description 1
- ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
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- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-M phenylacetate Chemical compound [O-]C(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-M 0.000 description 1
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- 230000001766 physiological effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960004583 pranlukast Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
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- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
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- 239000008213 purified water Substances 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- BMBATCYWJILFCR-UHFFFAOYSA-N s-(2-cyanoethyl) ethanethioate Chemical compound CC(=O)SCCC#N BMBATCYWJILFCR-UHFFFAOYSA-N 0.000 description 1
- ITOLADWLXDCGOA-UHFFFAOYSA-N s-[2-(2h-tetrazol-5-yl)ethyl] ethanethioate Chemical compound CC(=O)SCCC=1N=NNN=1 ITOLADWLXDCGOA-UHFFFAOYSA-N 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- DWRGLIHFAJTMGM-UHFFFAOYSA-N thiohydroxylamine;hydrochloride Chemical compound Cl.SN DWRGLIHFAJTMGM-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 239000003643 water by type Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Otolaryngology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Polyurethanes Or Polyureas (AREA)
- Hydrogenated Pyridines (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Paints Or Removers (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200202590A ES2211315B1 (es) | 2002-11-12 | 2002-11-12 | Nuevos compuestos triciclicos. |
| PCT/EP2003/012581 WO2004043966A1 (en) | 2002-11-12 | 2003-11-11 | New tricyclic derivatives as ltd4 antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006508116A true JP2006508116A (ja) | 2006-03-09 |
| JP2006508116A5 JP2006508116A5 (enExample) | 2006-11-24 |
Family
ID=32309630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004550982A Pending JP2006508116A (ja) | 2002-11-12 | 2003-11-11 | Ltd4アンタゴニストとしての新規三環式誘導体 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7557212B2 (enExample) |
| EP (1) | EP1560834B1 (enExample) |
| JP (1) | JP2006508116A (enExample) |
| KR (1) | KR20050074605A (enExample) |
| CN (1) | CN100379742C (enExample) |
| AT (1) | ATE399170T1 (enExample) |
| AU (1) | AU2003288032A1 (enExample) |
| BR (1) | BR0315462A (enExample) |
| CA (1) | CA2505491A1 (enExample) |
| CO (1) | CO5700775A2 (enExample) |
| DE (1) | DE60321810D1 (enExample) |
| EC (1) | ECSP055844A (enExample) |
| ES (2) | ES2211315B1 (enExample) |
| MX (1) | MXPA05005017A (enExample) |
| NO (1) | NO20052858L (enExample) |
| RU (1) | RU2330855C2 (enExample) |
| UA (1) | UA80996C2 (enExample) |
| WO (1) | WO2004043966A1 (enExample) |
| ZA (1) | ZA200503806B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017159618A1 (ja) * | 2016-03-18 | 2017-09-21 | 石原産業株式会社 | 有害生物防除剤 |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| US7214687B2 (en) | 1999-07-14 | 2007-05-08 | Almirall Ag | Quinuclidine derivatives and medicinal compositions containing the same |
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| CA2624656A1 (en) * | 2005-10-21 | 2007-05-03 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TW200813021A (en) | 2006-07-10 | 2008-03-16 | Merck & Co Inc | Tyrosine kinase inhibitors |
| ES2298049B1 (es) | 2006-07-21 | 2009-10-20 | Laboratorios Almirall S.A. | Procedimiento para fabricar bromuro de 3(r)-(2-hidroxi-2,2-ditien-2-ilacetoxi)-1-(3-fenoxipropil)-1-azoniabiciclo (2.2.2) octano. |
| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
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| EP2322176A1 (en) | 2009-11-11 | 2011-05-18 | Almirall, S.A. | New 7-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
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| WO2001047889A1 (en) * | 1999-12-28 | 2001-07-05 | Ube Industries, Ltd. | Tricyclic compounds |
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| CA1341044C (en) * | 1988-04-28 | 2000-07-04 | Frank J. Villani | Benzopyrido piperidine, piperidylidene and peperazine compounds, compositions, methods of manufacture and methods of use |
| ATE266025T1 (de) * | 1997-11-25 | 2004-05-15 | Schering Corp | Thrombin-rezeptor antagonisten |
| JP2006151809A (ja) * | 2002-12-26 | 2006-06-15 | Ube Ind Ltd | ベンゾシクロヘプタピリジン化合物 |
-
2002
- 2002-11-12 ES ES200202590A patent/ES2211315B1/es not_active Expired - Fee Related
-
2003
- 2003-11-11 MX MXPA05005017A patent/MXPA05005017A/es not_active Application Discontinuation
- 2003-11-11 KR KR1020057008474A patent/KR20050074605A/ko not_active Withdrawn
- 2003-11-11 ES ES03779886T patent/ES2306906T3/es not_active Expired - Lifetime
- 2003-11-11 WO PCT/EP2003/012581 patent/WO2004043966A1/en not_active Ceased
- 2003-11-11 BR BR0315462-9A patent/BR0315462A/pt not_active IP Right Cessation
- 2003-11-11 RU RU2005118757/04A patent/RU2330855C2/ru not_active IP Right Cessation
- 2003-11-11 EP EP03779886A patent/EP1560834B1/en not_active Expired - Lifetime
- 2003-11-11 AT AT03779886T patent/ATE399170T1/de not_active IP Right Cessation
- 2003-11-11 AU AU2003288032A patent/AU2003288032A1/en not_active Abandoned
- 2003-11-11 CA CA002505491A patent/CA2505491A1/en not_active Abandoned
- 2003-11-11 DE DE60321810T patent/DE60321810D1/de not_active Expired - Lifetime
- 2003-11-11 UA UAA200505509A patent/UA80996C2/uk unknown
- 2003-11-11 JP JP2004550982A patent/JP2006508116A/ja active Pending
- 2003-11-11 CN CNB2003801085261A patent/CN100379742C/zh not_active Expired - Fee Related
- 2003-11-11 US US10/534,487 patent/US7557212B2/en not_active Expired - Fee Related
-
2005
- 2005-05-11 ZA ZA200503806A patent/ZA200503806B/en unknown
- 2005-06-09 EC EC2005005844A patent/ECSP055844A/es unknown
- 2005-06-10 CO CO05056627A patent/CO5700775A2/es unknown
- 2005-06-13 NO NO20052858A patent/NO20052858L/no not_active Application Discontinuation
Patent Citations (3)
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| JPH03163075A (ja) * | 1989-08-22 | 1991-07-15 | Merck Frosst Canada Inc | ロイコトリエン類の生合成阻害剤としての(キノリン―2―イルメトキシ)インドール類 |
| WO1994019345A1 (fr) * | 1993-02-16 | 1994-09-01 | Ube Industries, Ltd. | Derive de quinoleine |
| WO2001047889A1 (en) * | 1999-12-28 | 2001-07-05 | Ube Industries, Ltd. | Tricyclic compounds |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2017159618A1 (ja) * | 2016-03-18 | 2017-09-21 | 石原産業株式会社 | 有害生物防除剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100379742C (zh) | 2008-04-09 |
| CN1735618A (zh) | 2006-02-15 |
| CA2505491A1 (en) | 2004-05-27 |
| US7557212B2 (en) | 2009-07-07 |
| ECSP055844A (es) | 2005-09-20 |
| US20060116363A1 (en) | 2006-06-01 |
| RU2005118757A (ru) | 2006-02-27 |
| CO5700775A2 (es) | 2006-11-30 |
| EP1560834A1 (en) | 2005-08-10 |
| ZA200503806B (en) | 2006-08-30 |
| ES2211315A1 (es) | 2004-07-01 |
| NO20052858D0 (no) | 2005-06-13 |
| MXPA05005017A (es) | 2005-08-03 |
| ATE399170T1 (de) | 2008-07-15 |
| AU2003288032A1 (en) | 2004-06-03 |
| ES2211315B1 (es) | 2005-10-16 |
| KR20050074605A (ko) | 2005-07-18 |
| EP1560834B1 (en) | 2008-06-25 |
| WO2004043966A1 (en) | 2004-05-27 |
| ES2306906T3 (es) | 2008-11-16 |
| DE60321810D1 (de) | 2008-08-07 |
| RU2330855C2 (ru) | 2008-08-10 |
| BR0315462A (pt) | 2005-08-23 |
| UA80996C2 (en) | 2007-11-26 |
| NO20052858L (no) | 2005-08-12 |
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