AU2005245104B2 - Novel cylopenta[b]benzofuran derivatives and the utilization thereof - Google Patents
Novel cylopenta[b]benzofuran derivatives and the utilization thereof Download PDFInfo
- Publication number
- AU2005245104B2 AU2005245104B2 AU2005245104A AU2005245104A AU2005245104B2 AU 2005245104 B2 AU2005245104 B2 AU 2005245104B2 AU 2005245104 A AU2005245104 A AU 2005245104A AU 2005245104 A AU2005245104 A AU 2005245104A AU 2005245104 B2 AU2005245104 B2 AU 2005245104B2
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- AU
- Australia
- Prior art keywords
- hydrogen
- formula
- alkylamino
- ethoxy
- substituted
- 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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- 150000001907 coumarones Chemical class 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 282
- 239000003814 drug Substances 0.000 claims abstract description 15
- 238000011321 prophylaxis Methods 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 277
- 239000001257 hydrogen Substances 0.000 claims description 197
- 229910052739 hydrogen Inorganic materials 0.000 claims description 197
- -1 benzyloxy, ethoxy, n-propoxy Chemical group 0.000 claims description 147
- 150000002431 hydrogen Chemical group 0.000 claims description 146
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 115
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 98
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 95
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 76
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 76
- 239000012453 solvate Substances 0.000 claims description 71
- 125000000623 heterocyclic group Chemical group 0.000 claims description 69
- 229910052736 halogen Inorganic materials 0.000 claims description 67
- 150000002367 halogens Chemical class 0.000 claims description 67
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 51
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 44
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 239000000460 chlorine Substances 0.000 claims description 38
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 35
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 208000035475 disorder Diseases 0.000 claims description 27
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 26
- 239000011737 fluorine Substances 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 23
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 23
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 22
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 22
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 239000012442 inert solvent Substances 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 15
- 230000004913 activation Effects 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 12
- 230000003463 hyperproliferative effect Effects 0.000 claims description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 10
- 238000007796 conventional method Methods 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 10
- 125000001425 triazolyl group Chemical group 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 239000002841 Lewis acid Substances 0.000 claims description 5
- 150000001735 carboxylic acids Chemical class 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 150000007517 lewis acids Chemical class 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical class BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims 11
- 125000003282 alkyl amino group Chemical group 0.000 claims 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical group C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- 230000001154 acute effect Effects 0.000 abstract description 3
- 230000009885 systemic effect Effects 0.000 abstract description 3
- 208000017667 Chronic Disease Diseases 0.000 abstract description 2
- 230000004637 cellular stress Effects 0.000 abstract description 2
- 208000030090 Acute Disease Diseases 0.000 abstract 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 144
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 132
- 238000005160 1H NMR spectroscopy Methods 0.000 description 124
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 230000015572 biosynthetic process Effects 0.000 description 120
- 238000003786 synthesis reaction Methods 0.000 description 118
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 111
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 110
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 93
- 229910052740 iodine Inorganic materials 0.000 description 93
- 239000000203 mixture Substances 0.000 description 89
- 239000000243 solution Substances 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 79
- 239000003480 eluent Substances 0.000 description 75
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 239000012071 phase Substances 0.000 description 57
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 50
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 49
- 238000000825 ultraviolet detection Methods 0.000 description 44
- 210000004027 cell Anatomy 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 34
- 235000019253 formic acid Nutrition 0.000 description 34
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 33
- 229910052796 boron Inorganic materials 0.000 description 33
- 238000004128 high performance liquid chromatography Methods 0.000 description 33
- 239000000047 product Substances 0.000 description 33
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 32
- 238000011068 loading method Methods 0.000 description 31
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 125000004432 carbon atom Chemical group C* 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 102100023132 Transcription factor Jun Human genes 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- 239000000126 substance Substances 0.000 description 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 27
- 229910052786 argon Inorganic materials 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 108010018242 Transcription Factor AP-1 Proteins 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 23
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 206010028980 Neoplasm Diseases 0.000 description 19
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- 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 18
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 102000003945 NF-kappa B Human genes 0.000 description 17
- 108010057466 NF-kappa B Proteins 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 239000008346 aqueous phase Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 238000007792 addition Methods 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 238000000926 separation method Methods 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 229960001701 chloroform Drugs 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 238000001816 cooling Methods 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 12
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 12
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- 238000004587 chromatography analysis Methods 0.000 description 12
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
- 229910052708 sodium Inorganic materials 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- 102000004890 Interleukin-8 Human genes 0.000 description 11
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 11
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- 238000003756 stirring Methods 0.000 description 11
- JPCVUDRCLISCMI-UHFFFAOYSA-N 2-bromo-6-(2-chloroethoxy)-1-benzofuran-3-one Chemical compound ClCCOC1=CC=C2C(=O)C(Br)OC2=C1 JPCVUDRCLISCMI-UHFFFAOYSA-N 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 229910052783 alkali metal Inorganic materials 0.000 description 10
- 229950005499 carbon tetrachloride Drugs 0.000 description 10
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
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- 239000002253 acid Substances 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004024504.5 | 2004-05-18 | ||
| DE102004024504A DE102004024504A1 (de) | 2004-05-18 | 2004-05-18 | Neue Cylopenta[b]benzofuran-Derivate und ihre Verwendung |
| PCT/EP2005/005298 WO2005113529A2 (de) | 2004-05-18 | 2005-05-14 | Neue cylopenta[b]benzofuran-derivate und ihre verwendung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2005245104A1 AU2005245104A1 (en) | 2005-12-01 |
| AU2005245104B2 true AU2005245104B2 (en) | 2011-07-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2005245104A Ceased AU2005245104B2 (en) | 2004-05-18 | 2005-05-14 | Novel cylopenta[b]benzofuran derivatives and the utilization thereof |
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| Country | Link |
|---|---|
| US (1) | US8030347B2 (https=) |
| EP (1) | EP1751127B1 (https=) |
| JP (1) | JP2007538031A (https=) |
| KR (1) | KR101215164B1 (https=) |
| CN (1) | CN1989122B (https=) |
| AU (1) | AU2005245104B2 (https=) |
| BR (1) | BRPI0510403A (https=) |
| CA (1) | CA2567404C (https=) |
| DE (1) | DE102004024504A1 (https=) |
| IL (1) | IL179257A (https=) |
| MX (1) | MXPA06013182A (https=) |
| RU (1) | RU2415847C9 (https=) |
| WO (1) | WO2005113529A2 (https=) |
| ZA (1) | ZA200609444B (https=) |
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| EP1771169A1 (en) | 2004-07-14 | 2007-04-11 | PTC Therapeutics, Inc. | Methods for treating hepatitis c |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| EP1693059A1 (en) * | 2005-02-22 | 2006-08-23 | Deutsches Krebsforschungszentrum | Use of rocaglamide derivatives as NF-AT-specific inhibitors for the treatment of certain inflammatory diseases |
| EP2189453A1 (en) * | 2008-11-25 | 2010-05-26 | Université Louis Pasteur | Rocaglaol derivatives as cardioprotectant agents |
| EP2457907A1 (en) * | 2010-11-16 | 2012-05-30 | Université de Strasbourg | Flavagline derivatives as neuroprotective agents |
| US20140255432A1 (en) * | 2011-07-27 | 2014-09-11 | Ohio State Innovation Foundation | Silvestrol, silvestrol analogs and uses thereof |
| FR3023290B1 (fr) * | 2014-07-04 | 2016-08-19 | Pf Medicament | Derives de flavaglines |
| EP3888658B1 (en) | 2015-11-25 | 2023-12-27 | Effector Therapeutics, Inc. | Eif4-a-inhibiting compounds and methods related thereto |
| EP3755693B1 (en) | 2018-02-19 | 2024-06-12 | Memorial Sloan-Kettering Cancer Center | Agents and methods for treating dysproliferative diseases |
| EP3639820A1 (en) | 2018-10-16 | 2020-04-22 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Flavagline derivatives for inhibition of kras oncogene activation |
| CN110646616B (zh) * | 2019-09-05 | 2023-05-30 | 桂林理工大学 | 一种检测血清中人cTnI的超敏荧光猝灭免疫传感器及检测方法 |
| CN110776486B (zh) * | 2019-10-23 | 2022-05-20 | 中国药科大学 | 一种苯并呋喃类小分子p2y14受体抑制剂，及其制备和应用 |
| CA3230542A1 (en) | 2021-09-01 | 2023-03-09 | Krishnaraj Rajalingam | Novel ras inhibitors |
| CN116077483A (zh) * | 2021-11-05 | 2023-05-09 | 上海中医药大学 | 楝酰胺及其类似物的药物用途 |
| CN115385924B (zh) * | 2022-10-06 | 2023-10-13 | 贵州省中国科学院天然产物化学重点实验室(贵州医科大学天然产物化学重点实验室) | 一种具有抗肿瘤活性的环戊烷苯并呋喃类化合物及其应用 |
| WO2024175662A1 (en) | 2023-02-23 | 2024-08-29 | KHR Biotec GmbH | Flavagline derivatives as ras inhibitors |
| JP2026508161A (ja) | 2023-02-23 | 2026-03-10 | エスジェーピー バイオテック ゲーエムベーハー | 新規ＲＡＳ阻害剤３ａＨ－シクロペンタ［ｂ］ベンゾフラン－３ａ－イル |
| WO2025092976A1 (zh) * | 2023-11-03 | 2025-05-08 | 映恩生物制药（苏州）有限公司 | 蛋白翻译抑制剂 |
| TW202545938A (zh) * | 2024-01-16 | 2025-12-01 | 大陸商映恩生物製藥（蘇州）有限公司 | 一種蛋白轉譯抑制劑的偶聯物及其用途 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000007579A2 (de) * | 1998-08-05 | 2000-02-17 | Bayer Aktiengesellschaft | VERWENDUNG VON CYCLOPENTABENZOFURANDERIVATEN ZUR BEKÄMPFUNG VON NF-λB-ABHÄNGIGEN KRANKHEITEN |
| WO2000008007A2 (de) * | 1998-08-05 | 2000-02-17 | Bayer Aktiengesellschaft | Cyclopentabenzofuran-derivate und ihre verwendung |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU191264B (en) * | 1984-01-13 | 1987-01-28 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt,Hu | Process for production of derivatives of 7-oxo-prostacyclin with selective biological effect |
| KR100381584B1 (ko) * | 1994-07-22 | 2003-08-21 | 알타나 파마 아게 | 디히드로벤조푸란 |
| DE19934952A1 (de) * | 1998-07-30 | 2000-02-03 | Novartis Ag | Cyclopentabenzofuran-Derivate |
| DE10158561A1 (de) * | 2001-11-29 | 2003-06-12 | Bayer Ag | Neue Verwendung von Cyclopentabenzofuranen |
-
2004
- 2004-05-18 DE DE102004024504A patent/DE102004024504A1/de not_active Withdrawn
-
2005
- 2005-05-14 US US11/596,907 patent/US8030347B2/en not_active Expired - Fee Related
- 2005-05-14 EP EP05747405A patent/EP1751127B1/de not_active Expired - Lifetime
- 2005-05-14 BR BRPI0510403-3A patent/BRPI0510403A/pt not_active IP Right Cessation
- 2005-05-14 JP JP2007517059A patent/JP2007538031A/ja active Pending
- 2005-05-14 CN CN2005800241153A patent/CN1989122B/zh not_active Expired - Fee Related
- 2005-05-14 CA CA2567404A patent/CA2567404C/en not_active Expired - Fee Related
- 2005-05-14 MX MXPA06013182A patent/MXPA06013182A/es active IP Right Grant
- 2005-05-14 RU RU2006144710/04A patent/RU2415847C9/ru not_active IP Right Cessation
- 2005-05-14 AU AU2005245104A patent/AU2005245104B2/en not_active Ceased
- 2005-05-14 WO PCT/EP2005/005298 patent/WO2005113529A2/de not_active Ceased
-
2006
- 2006-11-14 IL IL179257A patent/IL179257A/en not_active IP Right Cessation
- 2006-11-14 ZA ZA200609444A patent/ZA200609444B/en unknown
- 2006-11-17 KR KR1020067024170A patent/KR101215164B1/ko not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000007579A2 (de) * | 1998-08-05 | 2000-02-17 | Bayer Aktiengesellschaft | VERWENDUNG VON CYCLOPENTABENZOFURANDERIVATEN ZUR BEKÄMPFUNG VON NF-λB-ABHÄNGIGEN KRANKHEITEN |
| WO2000008007A2 (de) * | 1998-08-05 | 2000-02-17 | Bayer Aktiengesellschaft | Cyclopentabenzofuran-derivate und ihre verwendung |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005245104A1 (en) | 2005-12-01 |
| DE102004024504A1 (de) | 2006-02-16 |
| CN1989122B (zh) | 2013-07-24 |
| ZA200609444B (en) | 2008-01-30 |
| RU2006144710A (ru) | 2008-06-27 |
| JP2007538031A (ja) | 2007-12-27 |
| IL179257A0 (en) | 2007-03-08 |
| RU2415847C2 (ru) | 2011-04-10 |
| EP1751127B1 (de) | 2012-07-11 |
| US20090018113A1 (en) | 2009-01-15 |
| EP1751127A2 (de) | 2007-02-14 |
| WO2005113529A2 (de) | 2005-12-01 |
| KR20070011522A (ko) | 2007-01-24 |
| WO2005113529A3 (de) | 2006-02-09 |
| US8030347B2 (en) | 2011-10-04 |
| KR101215164B1 (ko) | 2012-12-24 |
| CA2567404C (en) | 2014-04-01 |
| IL179257A (en) | 2013-02-28 |
| CA2567404A1 (en) | 2005-12-01 |
| RU2415847C9 (ru) | 2011-08-10 |
| BRPI0510403A (pt) | 2007-10-23 |
| MXPA06013182A (es) | 2007-02-14 |
| CN1989122A (zh) | 2007-06-27 |
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| PC1 | Assignment before grant (sect. 113) |
Owner name: INTERMED DISCOVERY GMBH Free format text: FORMER APPLICANT(S): BAYER HEALTHCARE AG |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |