JP5432246B2 - 治療的に有効な置換ヒドロピリド［３，２，１−ｉｊ］キノリン化合物 - Google Patents
治療的に有効な置換ヒドロピリド［３，２，１−ｉｊ］キノリン化合物 Download PDFInfo
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- JP5432246B2 JP5432246B2 JP2011508667A JP2011508667A JP5432246B2 JP 5432246 B2 JP5432246 B2 JP 5432246B2 JP 2011508667 A JP2011508667 A JP 2011508667A JP 2011508667 A JP2011508667 A JP 2011508667A JP 5432246 B2 JP5432246 B2 JP 5432246B2
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- Prior art keywords
- alkyl
- hexahydropyrido
- diphenyl
- group
- compound
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- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
- -1 3-trifluoromethylphenyl Chemical group 0.000 claims description 76
- 150000001875 compounds Chemical class 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 27
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 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
- 208000002193 Pain Diseases 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 230000036407 pain Effects 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- 206010061323 Optic neuropathy Diseases 0.000 claims description 4
- 208000020911 optic nerve disease Diseases 0.000 claims description 4
- 230000029663 wound healing Effects 0.000 claims description 4
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 3
- 206010013774 Dry eye Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 230000033115 angiogenesis Effects 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 231100000241 scar Toxicity 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 208000008035 Back Pain Diseases 0.000 claims description 2
- 206010058019 Cancer Pain Diseases 0.000 claims description 2
- 208000005590 Choroidal Neovascularization Diseases 0.000 claims description 2
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- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010013975 Dyspnoeas Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 2
- 208000033463 Ischaemic neuropathy Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000000112 Myalgia Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 0.000 claims description 2
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 2
- 206010072170 Skin wound Diseases 0.000 claims description 2
- 208000010285 Ventilator-Induced Lung Injury Diseases 0.000 claims description 2
- 208000012871 acute dyspnea Diseases 0.000 claims description 2
- 206010069351 acute lung injury Diseases 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 208000006218 bradycardia Diseases 0.000 claims description 2
- 230000036471 bradycardia Effects 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
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- 230000035876 healing Effects 0.000 claims description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 208000002780 macular degeneration Diseases 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 208000013465 muscle pain Diseases 0.000 claims description 2
- 230000002207 retinal effect Effects 0.000 claims description 2
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- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
- 206010030113 Oedema Diseases 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 230000004410 intraocular pressure Effects 0.000 claims 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 208000004296 neuralgia Diseases 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 210000001525 retina Anatomy 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 238000005481 NMR spectroscopy Methods 0.000 description 44
- 125000001183 hydrocarbyl group Chemical group 0.000 description 43
- 125000003118 aryl group Chemical group 0.000 description 38
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 37
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 30
- 150000002431 hydrogen Chemical group 0.000 description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 27
- 125000003545 alkoxy group Chemical group 0.000 description 26
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 26
- 125000004093 cyano group Chemical group *C#N 0.000 description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 24
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 22
- 125000003282 alkyl amino group Chemical group 0.000 description 21
- 125000005157 alkyl carboxy group Chemical group 0.000 description 20
- 229910052786 argon Inorganic materials 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 125000005243 carbonyl alkyl group Chemical group 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 13
- 125000000524 functional group Chemical group 0.000 description 13
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 125000000623 heterocyclic group Chemical group 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000004043 oxo group Chemical group O=* 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 150000003408 sphingolipids Chemical class 0.000 description 6
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 229940106189 ceramide Drugs 0.000 description 5
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 5
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- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 5
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- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 4
- ZPLLXGJVIAAKHK-UHFFFAOYSA-N 1,7-diphenyl-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinoline-9-carboxylic acid Chemical compound C1=2C3=CC(C(=O)O)=CC=2C(C=2C=CC=CC=2)CCN1CCC3C1=CC=CC=C1 ZPLLXGJVIAAKHK-UHFFFAOYSA-N 0.000 description 4
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
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- 229910019142 PO4 Inorganic materials 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
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- 150000001412 amines Chemical group 0.000 description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- ZTLSFLYGVOUTFI-UHFFFAOYSA-N methyl 1,7-diphenyl-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-ylcarbamate Chemical compound C1=2C3=CC(NC(=O)OC)=CC=2C(C=2C=CC=CC=2)CCN1CCC3C1=CC=CC=C1 ZTLSFLYGVOUTFI-UHFFFAOYSA-N 0.000 description 4
- CANLDFLYBBBTKC-UHFFFAOYSA-N n-butyl-1,7-diphenyl-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinoline-9-carboxamide Chemical compound C1=2C3=CC(C(=O)NCCCC)=CC=2C(C=2C=CC=CC=2)CCN1CCC3C1=CC=CC=C1 CANLDFLYBBBTKC-UHFFFAOYSA-N 0.000 description 4
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- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 4
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
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- ARFDAFPFUOXGEM-UHFFFAOYSA-N 1,7-dimethyl-9-nitro-1,7-diphenyl-2,3,6,7-tetrahydro-1h,5h-pyrido[3,2,1-ij]quinoline Chemical compound C=12C3=CC([N+]([O-])=O)=CC=1C(C)(C=1C=CC=CC=1)CCN2CCC3(C)C1=CC=CC=C1 ARFDAFPFUOXGEM-UHFFFAOYSA-N 0.000 description 3
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- OKBPVNFRQFNRPH-UHFFFAOYSA-N 3-(1,7-diphenyl-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-yl)-1,1-dimethylurea Chemical compound C1=2C3=CC(NC(=O)N(C)C)=CC=2C(C=2C=CC=CC=2)CCN1CCC3C1=CC=CC=C1 OKBPVNFRQFNRPH-UHFFFAOYSA-N 0.000 description 3
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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- 239000002253 acid Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
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- 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
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- 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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- 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
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- C07D471/12—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 three hetero rings
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5153308P | 2008-05-08 | 2008-05-08 | |
| US61/051,533 | 2008-05-08 | ||
| US12/433,978 US20090281322A1 (en) | 2008-05-08 | 2009-05-01 | THERAPEUTICALLY USEFUL SUBSTITUTED 1,7-DIPHENYL-1,2,3,5,6,7-HEXAHYDROPYRIDO[3,2,1-Ij]QUINOLINE COMPOUNDS |
| US12/433,978 | 2009-05-01 | ||
| PCT/US2009/043149 WO2009137681A1 (en) | 2008-05-08 | 2009-05-07 | Therapeutically useful substituted hydropyrido [3,2,1-ij] quinoline compounds |
Publications (3)
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| JP2011527286A JP2011527286A (ja) | 2011-10-27 |
| JP2011527286A5 JP2011527286A5 (enExample) | 2012-06-21 |
| JP5432246B2 true JP5432246B2 (ja) | 2014-03-05 |
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| JP (1) | JP5432246B2 (enExample) |
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| EP2688593A2 (en) * | 2011-03-25 | 2014-01-29 | Allergan, Inc. | S1p antagonists as adjunct ocular hypotensives |
| KR101691954B1 (ko) * | 2016-04-26 | 2017-01-02 | 고려대학교 산학협력단 | 신규 n-아실유레아 유도체 및 이를 함유하는 심혈관질환의 예방 또는 치료용 조성물 |
| CN107369775B (zh) * | 2017-07-13 | 2018-12-25 | 长春海谱润斯科技有限公司 | 一种有机电致发光材料及其有机发光器件 |
| CN107492597B (zh) * | 2017-08-10 | 2018-11-27 | 长春海谱润斯科技有限公司 | 一种顶发射有机发光器件 |
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| AU2003214873A1 (en) * | 2002-01-18 | 2003-09-02 | Ceretek Llc | Methods of treating conditions associated with an edg receptor |
| MXPA05002007A (es) * | 2002-09-17 | 2005-04-28 | Warner Lambert Co | Piperazinas heterociclicas sustituidas para el tratamiento de la esquizofrenia. |
| US20040131648A1 (en) * | 2002-10-24 | 2004-07-08 | The Procter & Gamble Company | Nuclear hormone receptor compounds, products and methods employing same |
| US20040167185A1 (en) * | 2003-01-16 | 2004-08-26 | Geetha Shankar | Methods of treating conditions associated with an Edg-3 receptor |
| EP2298770A1 (en) * | 2005-11-03 | 2011-03-23 | ChemBridge Corporation | Heterocyclic compounds as TrkA modulators |
| US8097644B2 (en) * | 2006-03-28 | 2012-01-17 | Allergan, Inc. | Indole compounds having sphingosine-1-phosphate (S1P) receptor antagonist |
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2009
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- 2009-05-07 RU RU2010149312/04A patent/RU2010149312A/ru not_active Application Discontinuation
- 2009-05-07 CA CA2723798A patent/CA2723798A1/en not_active Abandoned
- 2009-05-07 JP JP2011508667A patent/JP5432246B2/ja not_active Expired - Fee Related
- 2009-05-07 CN CN2009801266353A patent/CN102089306A/zh active Pending
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- 2009-05-07 AU AU2009244199A patent/AU2009244199B2/en not_active Ceased
- 2009-05-07 WO PCT/US2009/043149 patent/WO2009137681A1/en not_active Ceased
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2010
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Also Published As
| Publication number | Publication date |
|---|---|
| US20090281322A1 (en) | 2009-11-12 |
| BRPI0912534A2 (pt) | 2015-10-13 |
| CA2723798A1 (en) | 2009-11-12 |
| IL209200A0 (en) | 2011-01-31 |
| EP2294069A1 (en) | 2011-03-16 |
| AU2009244199B2 (en) | 2013-09-19 |
| JP2011527286A (ja) | 2011-10-27 |
| RU2010149312A (ru) | 2012-06-20 |
| AU2009244199A1 (en) | 2011-10-06 |
| WO2009137681A1 (en) | 2009-11-12 |
| CN102089306A (zh) | 2011-06-08 |
| EP2294069B1 (en) | 2015-09-02 |
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