CA2567404C - Cyclopenta[b]benzofuran derivatives and the utilization thereof - Google Patents
Cyclopenta[b]benzofuran derivatives and the utilization thereof Download PDFInfo
- Publication number
- CA2567404C CA2567404C CA2567404A CA2567404A CA2567404C CA 2567404 C CA2567404 C CA 2567404C CA 2567404 A CA2567404 A CA 2567404A CA 2567404 A CA2567404 A CA 2567404A CA 2567404 C CA2567404 C CA 2567404C
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- Canada
- Prior art keywords
- formula
- hydrogen
- 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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- HYGDHSYCSJKRFX-UHFFFAOYSA-N 1h-cyclopenta[b][1]benzofuran Chemical class O1C2=CC=CC=C2C2=C1C=CC2 HYGDHSYCSJKRFX-UHFFFAOYSA-N 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 278
- 230000008569 process Effects 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 238000011321 prophylaxis Methods 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 277
- 229910052739 hydrogen Inorganic materials 0.000 claims description 204
- 239000001257 hydrogen Substances 0.000 claims description 204
- 150000002431 hydrogen Chemical class 0.000 claims description 164
- -1 benzyloxy, ethoxy, n-propoxy Chemical group 0.000 claims description 125
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 117
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 101
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 98
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 89
- 150000003839 salts Chemical class 0.000 claims description 84
- 239000012453 solvate Substances 0.000 claims description 79
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 78
- 125000000623 heterocyclic group Chemical group 0.000 claims description 73
- 229910052736 halogen Chemical group 0.000 claims description 70
- 150000002367 halogens Chemical group 0.000 claims description 70
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 69
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 63
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 58
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 239000000460 chlorine Substances 0.000 claims description 31
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 27
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 26
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 26
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 239000011737 fluorine Substances 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 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
- 208000035475 disorder Diseases 0.000 claims description 22
- 239000012442 inert solvent Substances 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- 230000004913 activation Effects 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 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
- 125000003226 pyrazolyl 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
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 238000007796 conventional method Methods 0.000 claims description 7
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
- 230000003463 hyperproliferative effect Effects 0.000 claims description 6
- 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
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 4
- 150000007517 lewis acids Chemical class 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 12
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 208000027866 inflammatory disease Diseases 0.000 claims 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 7
- 230000004054 inflammatory process Effects 0.000 abstract description 5
- 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
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 232
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 143
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 132
- 208000012601 choreatic disease Diseases 0.000 description 129
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 230000015572 biosynthetic process Effects 0.000 description 121
- 238000003786 synthesis reaction Methods 0.000 description 119
- 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 105
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 93
- 239000000203 mixture Substances 0.000 description 89
- 239000000243 solution Substances 0.000 description 84
- 238000005160 1H NMR spectroscopy Methods 0.000 description 79
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- 239000003480 eluent Substances 0.000 description 74
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- 239000012071 phase Substances 0.000 description 57
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- 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
- 238000005481 NMR spectroscopy Methods 0.000 description 45
- 210000004027 cell Anatomy 0.000 description 42
- 238000000825 ultraviolet detection Methods 0.000 description 42
- 235000019253 formic acid Nutrition 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
- 102100023132 Transcription factor Jun Human genes 0.000 description 32
- 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
- 238000011068 loading method Methods 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- 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 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 108010018242 Transcription Factor AP-1 Proteins 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
- 229910052786 argon Inorganic materials 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 22
- 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
- 239000002585 base Substances 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 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
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
- 206010028980 Neoplasm Diseases 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 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
- 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
- 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
- 108090000623 proteins and genes Proteins 0.000 description 13
- 239000011734 sodium Substances 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
- 108090001007 Interleukin-8 Proteins 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(II) bromide Substances [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 12
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- 102000004890 Interleukin-8 Human genes 0.000 description 11
- 229910052783 alkali metal Inorganic materials 0.000 description 11
- 238000002474 experimental method Methods 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
- 229940096397 interleukin-8 Drugs 0.000 description 11
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 11
- 235000011181 potassium carbonates Nutrition 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 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
- 229960000583 acetic acid Drugs 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 229950005499 carbon tetrachloride Drugs 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
- 102000040945 Transcription factor Human genes 0.000 description 9
- 108091023040 Transcription factor Proteins 0.000 description 9
- 150000001340 alkali metals Chemical class 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
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- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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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 |
|---|---|
| CA2567404A1 CA2567404A1 (en) | 2005-12-01 |
| CA2567404C true CA2567404C (en) | 2014-04-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2567404A Expired - Fee Related CA2567404C (en) | 2004-05-18 | 2005-05-14 | Cyclopenta[b]benzofuran derivatives and the utilization thereof |
Country Status (14)
| 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=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (6)
| 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 |
| DE19835325A1 (de) * | 1998-08-05 | 2000-02-10 | Bayer Ag | Verwendung von Cyclopentabenzofuran-Derivaten zur Bekämpfung von NF-kB abhängigen Krankheiten |
| DE19835324A1 (de) * | 1998-08-05 | 2000-02-10 | Bayer Ag | Cyclopentabenzofuran-Derivate und ihre Verwendung |
| DE10158561A1 (de) * | 2001-11-29 | 2003-06-12 | Bayer Ag | Neue Verwendung von Cyclopentabenzofuranen |
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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
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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
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 |
| IL179257A (en) | 2013-02-28 |
| AU2005245104B2 (en) | 2011-07-28 |
| 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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