DK3164393T3 - Flavagline derivatives - Google Patents
Flavagline derivatives Download PDFInfo
- Publication number
- DK3164393T3 DK3164393T3 DK15733767.6T DK15733767T DK3164393T3 DK 3164393 T3 DK3164393 T3 DK 3164393T3 DK 15733767 T DK15733767 T DK 15733767T DK 3164393 T3 DK3164393 T3 DK 3164393T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- formula
- alkyl
- aryl
- group
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 209
- 125000000217 alkyl group Chemical group 0.000 claims description 157
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 83
- 238000000034 method Methods 0.000 claims description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 65
- 239000000203 mixture Substances 0.000 claims description 62
- 125000003118 aryl group Chemical group 0.000 claims description 59
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- 238000006467 substitution reaction Methods 0.000 claims description 42
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 34
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 30
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims description 24
- 238000006722 reduction reaction Methods 0.000 claims description 20
- 230000009467 reduction Effects 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 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 claims description 11
- 238000005906 dihydroxylation reaction Methods 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 238000006268 reductive amination reaction Methods 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 101100478297 Arabidopsis thaliana SR45 gene Proteins 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 229920000768 polyamine Polymers 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 4
- 150000003852 triazoles Chemical class 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000004866 oxadiazoles Chemical class 0.000 claims description 3
- 229910052705 radium Inorganic materials 0.000 claims description 3
- 229910052701 rubidium Inorganic materials 0.000 claims description 3
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 2
- 150000002540 isothiocyanates Chemical class 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 21
- JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 claims 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 229910019213 POCl3 Inorganic materials 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 claims 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 89
- 239000007787 solid Substances 0.000 description 79
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 54
- 238000005481 NMR spectroscopy Methods 0.000 description 52
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 238000003756 stirring Methods 0.000 description 29
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 28
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 28
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 28
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 28
- 125000000623 heterocyclic group Chemical group 0.000 description 28
- -1 aluminum ion Chemical class 0.000 description 27
- 239000003480 eluent Substances 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- 239000012141 concentrate Substances 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- 229960001866 silicon dioxide Drugs 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 20
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 18
- 150000001540 azides Chemical class 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 125000005842 heteroatom Chemical group 0.000 description 16
- 230000002194 synthesizing effect Effects 0.000 description 16
- 239000002585 base Substances 0.000 description 15
- SYUDUCVHYKSSNV-UHFFFAOYSA-N 1-benzofuran-2-carbohydrazide Chemical compound C1=CC=C2OC(C(=O)NN)=CC2=C1 SYUDUCVHYKSSNV-UHFFFAOYSA-N 0.000 description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
- 239000001301 oxygen Substances 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 238000007248 oxidative elimination reaction Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 150000002357 guanidines Chemical class 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- GVKXFVCXBFGBCD-UHFFFAOYSA-N silvestrol Natural products COC1OCC(C(O)CO)OC1OC(C=C1OC)=CC2=C1C1(O)C(O)C(C(=O)OC)C(C=3C=CC=CC=3)C1(C=1C=CC(OC)=CC=1)O2 GVKXFVCXBFGBCD-UHFFFAOYSA-N 0.000 description 8
- GVKXFVCXBFGBCD-QKDMMWSPSA-N silvestrol Chemical compound CO[C@@H]1OC[C@H]([C@H](O)CO)O[C@H]1OC(C=C1OC)=CC2=C1[C@]1(O)[C@H](O)[C@H](C(=O)OC)[C@@H](C=3C=CC=CC=3)[C@]1(C=1C=CC(OC)=CC=1)O2 GVKXFVCXBFGBCD-QKDMMWSPSA-N 0.000 description 8
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 125000005605 benzo group Chemical group 0.000 description 6
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 5
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- WHLAXDUXKMECTM-UHFFFAOYSA-N oxadiazol-4-amine Chemical compound NC1=CON=N1 WHLAXDUXKMECTM-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
- PGHKJMVOHWKSLJ-UHFFFAOYSA-N 2-methoxyethyl n-(2-methoxyethoxycarbonylimino)carbamate Chemical compound COCCOC(=O)N=NC(=O)OCCOC PGHKJMVOHWKSLJ-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- DAPAQENNNINUPW-IDAMAFBJSA-N rocaglamide Chemical compound C1=CC(OC)=CC=C1[C@]1([C@@H]([C@H]([C@H]2O)C(=O)N(C)C)C=3C=CC=CC=3)[C@]2(O)C2=C(OC)C=C(OC)C=C2O1 DAPAQENNNINUPW-IDAMAFBJSA-N 0.000 description 4
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- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 4
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- OLSQJCVHFHLFLH-XLNRJJMWSA-N (2Z)-2-(dimethylaminomethylidene)-8b-hydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-3-phenyl-3H-cyclopenta[b][1]benzofuran-1-one Chemical compound CN(C)\C=C\1/C(C2(C(OC3=C2C(=CC(=C3)OC)OC)(C/1C1=CC=CC=C1)C1=CC=C(C=C1)OC)O)=O OLSQJCVHFHLFLH-XLNRJJMWSA-N 0.000 description 3
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 3
- QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 description 3
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- 206010009944 Colon cancer Diseases 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
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- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1456474A FR3023290B1 (fr) | 2014-07-04 | 2014-07-04 | Derives de flavaglines |
| PCT/EP2015/065294 WO2016001441A1 (fr) | 2014-07-04 | 2015-07-06 | Dérivés de flavaglines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK3164393T3 true DK3164393T3 (en) | 2019-01-21 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK18187037.9T DK3418273T3 (da) | 2014-07-04 | 2015-07-06 | Derivater af flavagliner |
| DK15733767.6T DK3164393T3 (en) | 2014-07-04 | 2015-07-06 | Flavagline derivatives |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK18187037.9T DK3418273T3 (da) | 2014-07-04 | 2015-07-06 | Derivater af flavagliner |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US10047064B2 (OSRAM) |
| EP (3) | EP3418273B1 (OSRAM) |
| JP (4) | JP6637954B2 (OSRAM) |
| DK (2) | DK3418273T3 (OSRAM) |
| ES (2) | ES2700156T3 (OSRAM) |
| FR (1) | FR3023290B1 (OSRAM) |
| PL (2) | PL3164393T3 (OSRAM) |
| TR (1) | TR201819805T4 (OSRAM) |
| WO (1) | WO2016001441A1 (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| LT3643707T (lt) * | 2017-06-19 | 2022-05-25 | Futurechem Co., Ltd. | 18f žymėtas junginys, skirtas prostatos vėžio diagnostikai ir jo panaudojimas |
| KR20200123184A (ko) | 2018-02-19 | 2020-10-28 | 메모리얼 슬로안 케터링 캔서 센터 | 증식이상 장애를 치료하기 위한 물질 및 방법 |
| US12403121B2 (en) * | 2018-10-09 | 2025-09-02 | The Research Institute At Nationwide Children's Hospital | Anticancer rocaglamide derivatives |
| US11427595B2 (en) * | 2018-10-22 | 2022-08-30 | Trustees Of Boston University | Compositions and methods for inhibiting viral infection |
| EP4041718A4 (en) | 2019-10-10 | 2023-12-20 | Cellectar Biosciences, Inc. | PHOSPHOLIPIDE-FLVAGLIN CONJUGATES AND METHOD FOR THE USE THEREOF FOR TARGETED CANCER THERAPY |
| WO2025104293A1 (en) * | 2023-11-17 | 2025-05-22 | Gustave Roussy Transfert | Inhibitors of eif4a and uses thereof |
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| AUPQ866500A0 (en) * | 2000-07-05 | 2000-08-03 | Exgenix Operations Pty Ltd | Therapeutic compounds and methods |
| DE102004024504A1 (de) | 2004-05-18 | 2006-02-16 | Bayer Healthcare Ag | Neue Cylopenta[b]benzofuran-Derivate und ihre Verwendung |
| US8137509B2 (en) * | 2006-05-22 | 2012-03-20 | Trustees Of Boston University | Asymmetric synthesis of rocaglamides via enantioselective photocycloaddition mediated by chiral brønsted acids |
| EP2189453A1 (en) * | 2008-11-25 | 2010-05-26 | Université Louis Pasteur | Rocaglaol derivatives as cardioprotectant agents |
| MX2011005482A (es) * | 2008-12-05 | 2011-06-16 | Intermed Discovery Gmbh | Inhibidores de acumulacion de la proteina del factor 1 inducible por hipoxia. |
| FR3023290B1 (fr) * | 2014-07-04 | 2016-08-19 | Pf Medicament | Derives de flavaglines |
-
2014
- 2014-07-04 FR FR1456474A patent/FR3023290B1/fr active Active
-
2015
- 2015-07-06 DK DK18187037.9T patent/DK3418273T3/da active
- 2015-07-06 DK DK15733767.6T patent/DK3164393T3/en active
- 2015-07-06 TR TR2018/19805T patent/TR201819805T4/tr unknown
- 2015-07-06 EP EP18187037.9A patent/EP3418273B1/fr active Active
- 2015-07-06 ES ES15733767T patent/ES2700156T3/es active Active
- 2015-07-06 ES ES18187037T patent/ES2908225T3/es active Active
- 2015-07-06 EP EP21213303.7A patent/EP3998257A1/fr active Pending
- 2015-07-06 US US15/323,650 patent/US10047064B2/en active Active
- 2015-07-06 PL PL15733767T patent/PL3164393T3/pl unknown
- 2015-07-06 EP EP15733767.6A patent/EP3164393B1/fr active Active
- 2015-07-06 PL PL18187037.9T patent/PL3418273T3/pl unknown
- 2015-07-06 WO PCT/EP2015/065294 patent/WO2016001441A1/fr not_active Ceased
- 2015-07-06 JP JP2017500083A patent/JP6637954B2/ja active Active
-
2017
- 2017-12-01 US US15/829,630 patent/US10519125B2/en active Active
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2019
- 2019-12-20 JP JP2019230768A patent/JP6951406B2/ja active Active
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2021
- 2021-09-22 JP JP2021154798A patent/JP7340574B2/ja active Active
-
2023
- 2023-08-25 JP JP2023137552A patent/JP2023159393A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP3418273B1 (fr) | 2022-01-12 |
| ES2908225T3 (es) | 2022-04-28 |
| JP6951406B2 (ja) | 2021-10-20 |
| US20180086729A1 (en) | 2018-03-29 |
| PL3164393T3 (pl) | 2019-03-29 |
| JP2020063289A (ja) | 2020-04-23 |
| ES2700156T3 (es) | 2019-02-14 |
| JP2023159393A (ja) | 2023-10-31 |
| US20170137400A1 (en) | 2017-05-18 |
| FR3023290B1 (fr) | 2016-08-19 |
| TR201819805T4 (tr) | 2019-01-21 |
| JP2022000455A (ja) | 2022-01-04 |
| WO2016001441A1 (fr) | 2016-01-07 |
| JP7340574B2 (ja) | 2023-09-07 |
| US10519125B2 (en) | 2019-12-31 |
| US10047064B2 (en) | 2018-08-14 |
| EP3164393B1 (fr) | 2018-09-19 |
| JP2017519796A (ja) | 2017-07-20 |
| EP3418273A1 (fr) | 2018-12-26 |
| EP3164393A1 (fr) | 2017-05-10 |
| FR3023290A1 (fr) | 2016-01-08 |
| PL3418273T3 (pl) | 2022-08-01 |
| JP6637954B2 (ja) | 2020-01-29 |
| EP3998257A1 (fr) | 2022-05-18 |
| DK3418273T3 (da) | 2022-03-21 |
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