MX2007011666A - Derivados de fosforamidato de compuestos nucleosidicos para el uso en el tratamiento del cancer. - Google Patents
Derivados de fosforamidato de compuestos nucleosidicos para el uso en el tratamiento del cancer.Info
- Publication number
- MX2007011666A MX2007011666A MX2007011666A MX2007011666A MX2007011666A MX 2007011666 A MX2007011666 A MX 2007011666A MX 2007011666 A MX2007011666 A MX 2007011666A MX 2007011666 A MX2007011666 A MX 2007011666A MX 2007011666 A MX2007011666 A MX 2007011666A
- Authority
- MX
- Mexico
- Prior art keywords
- carbon atoms
- compound according
- treatment
- alkyl
- compound
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 16
- 201000011510 cancer Diseases 0.000 title claims abstract description 14
- 238000011282 treatment Methods 0.000 title claims description 31
- -1 nucleoside compounds Chemical class 0.000 title abstract description 23
- 239000002777 nucleoside Substances 0.000 title abstract description 5
- 150000008298 phosphoramidates Chemical class 0.000 title abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 42
- 208000032839 leukemia Diseases 0.000 claims abstract description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 150
- 150000001875 compounds Chemical class 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 22
- 229910019142 PO4 Inorganic materials 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 239000010452 phosphate Substances 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- 238000011321 prophylaxis Methods 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000006193 alkinyl group Chemical group 0.000 claims 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 abstract description 16
- 229960002436 cladribine Drugs 0.000 abstract description 11
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 abstract description 9
- 229960000928 clofarabine Drugs 0.000 abstract description 9
- 241000282414 Homo sapiens Species 0.000 abstract description 4
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 125000004437 phosphorous atom Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 17
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 12
- 101150041968 CDC13 gene Proteins 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 125000004122 cyclic group Chemical group 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 7
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000001093 anti-cancer Effects 0.000 description 6
- 229960000390 fludarabine Drugs 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000002015 acyclic group Chemical group 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
- 235000021317 phosphate Nutrition 0.000 description 5
- 238000010791 quenching Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000004679 31P NMR spectroscopy Methods 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 125000004663 dialkyl amino group Chemical group 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000012746 preparative thin layer chromatography Methods 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 3
- 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 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000000719 anti-leukaemic effect Effects 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
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- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
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- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
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- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
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- 230000004071 biological effect Effects 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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- ITVPBBDAZKBMRP-UHFFFAOYSA-N chloro-dioxido-oxo-$l^{5}-phosphane;hydron Chemical compound OP(O)(Cl)=O ITVPBBDAZKBMRP-UHFFFAOYSA-N 0.000 description 2
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- WUYMUVBIVVABRN-UHFFFAOYSA-N 1-[[4-[4-amino-5-(3-methoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]phenyl]methyl]piperidin-4-ol Chemical compound COC1=CC=CC(C=2C3=C(N)N=CN=C3N(C=3C=CC(CN4CCC(O)CC4)=CC=3)C=2)=C1 WUYMUVBIVVABRN-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
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- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
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| GBGB0505781.5A GB0505781D0 (en) | 2005-03-21 | 2005-03-21 | Chemical compounds |
| PCT/GB2006/000932 WO2006100439A1 (en) | 2005-03-21 | 2006-03-16 | Phosphoramidate derivatives of nucleoside compounds for use in the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007011666A true MX2007011666A (es) | 2007-11-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007011666A MX2007011666A (es) | 2005-03-21 | 2006-03-16 | Derivados de fosforamidato de compuestos nucleosidicos para el uso en el tratamiento del cancer. |
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| EP (1) | EP1866324B1 (enExample) |
| JP (2) | JP5345381B2 (enExample) |
| CN (2) | CN101175763A (enExample) |
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| AU (1) | AU2006226182C1 (enExample) |
| BR (1) | BRPI0609704B8 (enExample) |
| CA (1) | CA2602324C (enExample) |
| CY (1) | CY1111538T1 (enExample) |
| DE (1) | DE602006014949D1 (enExample) |
| DK (1) | DK1866324T3 (enExample) |
| ES (1) | ES2348741T3 (enExample) |
| GB (1) | GB0505781D0 (enExample) |
| IL (1) | IL186104A (enExample) |
| MX (1) | MX2007011666A (enExample) |
| PL (1) | PL1866324T3 (enExample) |
| PT (1) | PT1866324E (enExample) |
| SI (1) | SI1866324T1 (enExample) |
| WO (1) | WO2006100439A1 (enExample) |
| ZA (1) | ZA200709011B (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB0623493D0 (en) * | 2006-11-24 | 2007-01-03 | Univ Cardiff | Chemical compounds |
| AU2012216500B2 (en) * | 2006-11-24 | 2013-06-20 | Katholieke Universiteit Leuven | Nucleoside aryl phosphoramidates and their use as anti-viral agents for the treatment of hepatitis C virus |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| AR074897A1 (es) | 2008-12-23 | 2011-02-23 | Pharmasset Inc | Fosforamidatos de nucleosidos |
| CL2009002206A1 (es) | 2008-12-23 | 2011-08-26 | Gilead Pharmasset Llc | Compuestos derivados de pirrolo -(2-3-d]-pirimidin-7(6h)-tetrahidrofuran-2-il fosfonamidato, composicion farmaceutica; y su uso en el tratamiento de enfermedades virales. |
| MX2011006890A (es) | 2008-12-23 | 2011-07-20 | Pharmasset Inc | Analogos de nucleosidos. |
| BRPI1004575A2 (pt) | 2009-01-09 | 2016-04-05 | Inhibitex Inc | composto, composição farmacêutica, método de tratamento de infecções virais, método de separação dos diaestereômeros de fósforo |
| AP2012006535A0 (en) | 2010-03-31 | 2012-10-31 | Gilead Pharmasset Llc | Stereoselective synthesis of phosphorous containing actives |
| GB201016855D0 (en) * | 2010-10-06 | 2010-11-17 | Nucana Biomed Ltd | Chemical compounds |
| WO2012092484A2 (en) * | 2010-12-29 | 2012-07-05 | Inhibitex, Inc. | Substituted purine nucleosides, phosphoroamidate and phosphorodiamidate derivatives for treatment of viral infections |
| US9095599B2 (en) | 2011-01-03 | 2015-08-04 | Nanjing Molecular Research, Inc. | O-(substituted benzyl) phosphoramidate compounds and therapeutic use |
| ES2569185T3 (es) | 2011-03-01 | 2016-05-09 | Nucana Biomed Limited | Derivados de fosforamidato de 5-fluoro-2'-desoxiuridina para uso en el tratamiento del cáncer |
| US9085599B2 (en) | 2011-03-16 | 2015-07-21 | Enanta Pharmaceuticals, Inc. | 2′allene-substituted nucleoside derivatives |
| AU2013346515B2 (en) * | 2012-11-16 | 2017-05-25 | NuCana plc | Process for preparing nucleoside prodrugs |
| EP3004130B1 (en) | 2013-06-05 | 2019-08-07 | Idenix Pharmaceuticals LLC. | 1',4'-thio nucleosides for the treatment of hcv |
| JP2017504572A (ja) * | 2013-11-27 | 2017-02-09 | アイデニクス・ファーマシューティカルズ・エルエルシー | 肝臓癌治療のためのヌクレオチド類 |
| US20170101431A1 (en) * | 2014-05-28 | 2017-04-13 | Idenix Pharmaceuticals Llc | Nucleoside derivatives for the treatment of cancer |
| AU2015265607A1 (en) * | 2014-05-28 | 2016-11-17 | Idenix Pharmaceuticals Llc | Nucleoside derivatives for the treatment of cancer |
| HRP20191461T1 (hr) | 2014-11-28 | 2019-11-15 | NuCana plc | Novi 2' i/ili 5' derivati 3'-deoksi adenozina supstituirani aminokiselinskim esterom fosforamidata, kao antikancerogenog spoja |
| FI3265102T3 (fi) | 2015-03-06 | 2025-10-31 | Atea Pharmaceuticals Inc | Beta-d-2'-deoksi-2'-alfa-fluori-2'-beta-c-substituoituja-2-modifioituja-n6-substituoituja puriininukleotideja hcv-hoitoa varten |
| EP3377512A4 (en) * | 2015-11-16 | 2019-09-18 | Ichorion Therapeutics, Inc. | Nucleic Acid PRODRUGS |
| GB201522764D0 (en) * | 2015-12-23 | 2016-02-03 | Nucana Biomed Ltd | Formulations of phosphate derivatives |
| GB201609600D0 (en) * | 2016-06-01 | 2016-07-13 | Nucuna Biomed Ltd | Cancer treatments |
| GB201609601D0 (en) | 2016-06-01 | 2016-07-13 | Nucana Biomed Ltd | Phosphoramidate compounds |
| GB201609602D0 (en) * | 2016-06-01 | 2016-07-13 | Nucuna Biomed Ltd | Chemical compounds |
| WO2018013937A1 (en) | 2016-07-14 | 2018-01-18 | Atea Pharmaceuticals, Inc. | Beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| PT3512863T (pt) | 2016-09-07 | 2022-03-09 | Atea Pharmaceuticals Inc | Nucleótidos de purina 2'-substituídos-n6-substituídos para tratamento de vírus de rna |
| WO2018071675A1 (en) * | 2016-10-12 | 2018-04-19 | Georgetown University | Cd99 inhibitors and their uses |
| GB201709471D0 (en) | 2017-06-14 | 2017-07-26 | Nucana Biomed Ltd | Diastereoselective synthesis of hosphate derivatives |
| GB201715011D0 (en) | 2017-09-18 | 2017-11-01 | Nucana Biomed Ltd | Floxuridine synthesis |
| GB201720279D0 (en) | 2017-12-05 | 2018-01-17 | Nucana Biomed Ltd | Anticancer compounds |
| JP2020164521A (ja) * | 2019-03-29 | 2020-10-08 | 国立大学法人 長崎大学 | 抗ウィルス薬 |
| GB201904544D0 (en) | 2019-04-01 | 2019-05-15 | NuCana plc | Anticancer compounds |
| WO2021173713A1 (en) | 2020-02-27 | 2021-09-02 | Atea Pharmaceuticals, Inc. | Highly active compounds against covid-19 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| CN113549076B (zh) * | 2021-07-23 | 2022-12-06 | 中国药科大学 | 一种多取代嘌呤类化合物及其制备方法和应用 |
| WO2026151964A1 (en) | 2025-01-10 | 2026-07-16 | Atea Pharmaceuticals, Inc. | Compositions and use thereof in treating hepatitis e infections with beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides |
Family Cites Families (16)
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| KR880000094B1 (ko) | 1984-12-07 | 1988-02-23 | 보령제약 주식회사 | 뉴클레오시드 유도체의 제조방법 |
| CA2004695C (en) | 1988-12-12 | 1999-08-10 | Rosanne Bonjouklian | Phospholipid nucleosides |
| DE4418690A1 (de) * | 1994-05-28 | 1996-01-11 | Boehringer Mannheim Gmbh | Neue Lipidester von Nucleosid-Monophosphaten und deren Verwendung als immunsuppressive Arzneimittel |
| GB9505025D0 (en) * | 1995-03-13 | 1995-05-03 | Medical Res Council | Chemical compounds |
| EP0821692B1 (en) | 1995-04-21 | 2006-01-11 | University Of South Florida | Immunopotentiating inosine monophosphate 5'-nucleotidase resistant derivatives and uses thereof |
| JP3761958B2 (ja) | 1996-03-12 | 2006-03-29 | 彰 松田 | ３′−カルバモイルアルキルヌクレオシド誘導体 |
| ES2172303T3 (es) * | 1998-01-23 | 2002-09-16 | Newbiotics Inc | Agentes terapeuticos obtenidos por catalisis enzimatica. |
| GB9821058D0 (en) * | 1998-09-28 | 1998-11-18 | Univ Cardiff | Chemical compound |
| JP4768909B2 (ja) | 2000-09-29 | 2011-09-07 | 扶桑薬品工業株式会社 | トポイソメラーゼ阻害剤 |
| US20030073618A1 (en) * | 2001-02-08 | 2003-04-17 | Kozhemyakin Leonid A. | Compounds comprising disulfide-containing peptides and nitrogenous bases, and medical uses thereof |
| DE10108851A1 (de) * | 2001-02-23 | 2002-09-12 | Resprotect Gmbh | Verwendung von 5'-substituierten Nukleosiden und/oder deren Prodrugs zur resistenzfreien Therapie von Infektionskrankheiten |
| WO2003000200A2 (en) * | 2001-06-22 | 2003-01-03 | Pharmasset Ltd. | β-2'-OR 3'-HALONUCLEOSIDES |
| GB0317009D0 (en) | 2003-07-21 | 2003-08-27 | Univ Cardiff | Chemical compounds |
| GB0401088D0 (en) * | 2004-01-19 | 2004-02-18 | Univ Cardiff | Phosphoramidate derivatives |
| US20070265222A1 (en) * | 2004-06-24 | 2007-11-15 | Maccoss Malcolm | Nucleoside Aryl Phosphoramidates for the Treatment of Rna-Dependent Rna Viral Infection |
| CN101287472B (zh) * | 2005-08-15 | 2011-10-12 | 弗·哈夫曼-拉罗切有限公司 | 抗病毒的4'-取代前核苷酸的氨基磷酸酯类化合物 |
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2005
- 2005-03-21 GB GBGB0505781.5A patent/GB0505781D0/en not_active Ceased
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2006
- 2006-03-16 PL PL06710096T patent/PL1866324T3/pl unknown
- 2006-03-16 ES ES06710096T patent/ES2348741T3/es not_active Expired - Lifetime
- 2006-03-16 CN CNA200680016708XA patent/CN101175763A/zh active Pending
- 2006-03-16 MX MX2007011666A patent/MX2007011666A/es active IP Right Grant
- 2006-03-16 CA CA2602324A patent/CA2602324C/en not_active Expired - Lifetime
- 2006-03-16 CN CN201410186829.5A patent/CN103936807A/zh active Pending
- 2006-03-16 ZA ZA200709011A patent/ZA200709011B/xx unknown
- 2006-03-16 PT PT06710096T patent/PT1866324E/pt unknown
- 2006-03-16 SI SI200630762T patent/SI1866324T1/sl unknown
- 2006-03-16 AT AT06710096T patent/ATE471334T1/de active
- 2006-03-16 AU AU2006226182A patent/AU2006226182C1/en not_active Ceased
- 2006-03-16 BR BRPI0609704A patent/BRPI0609704B8/pt not_active IP Right Cessation
- 2006-03-16 US US11/886,931 patent/US8263575B2/en not_active Expired - Fee Related
- 2006-03-16 DK DK06710096.6T patent/DK1866324T3/da active
- 2006-03-16 JP JP2008502453A patent/JP5345381B2/ja not_active Expired - Fee Related
- 2006-03-16 DE DE602006014949T patent/DE602006014949D1/de not_active Expired - Lifetime
- 2006-03-16 WO PCT/GB2006/000932 patent/WO2006100439A1/en not_active Ceased
- 2006-03-16 EP EP06710096A patent/EP1866324B1/en not_active Expired - Lifetime
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2007
- 2007-09-20 IL IL186104A patent/IL186104A/en active IP Right Grant
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2010
- 2010-09-10 CY CY20101100826T patent/CY1111538T1/el unknown
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2013
- 2013-05-07 JP JP2013097919A patent/JP5863702B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2008533191A (ja) | 2008-08-21 |
| DE602006014949D1 (de) | 2010-07-29 |
| CN101175763A (zh) | 2008-05-07 |
| US8263575B2 (en) | 2012-09-11 |
| BRPI0609704A2 (pt) | 2010-04-20 |
| BRPI0609704B8 (pt) | 2021-09-28 |
| CA2602324A1 (en) | 2006-09-28 |
| CY1111538T1 (el) | 2015-08-05 |
| IL186104A (en) | 2013-06-27 |
| AU2006226182A1 (en) | 2006-09-28 |
| ATE471334T1 (de) | 2010-07-15 |
| ES2348741T3 (es) | 2010-12-13 |
| US20090215715A1 (en) | 2009-08-27 |
| AU2006226182B2 (en) | 2011-09-01 |
| IL186104A0 (en) | 2008-01-20 |
| JP5863702B2 (ja) | 2016-02-17 |
| PL1866324T3 (pl) | 2010-12-31 |
| AU2006226182C1 (en) | 2012-06-14 |
| GB0505781D0 (en) | 2005-04-27 |
| WO2006100439A1 (en) | 2006-09-28 |
| EP1866324A1 (en) | 2007-12-19 |
| BRPI0609704B1 (pt) | 2020-12-01 |
| PT1866324E (pt) | 2010-09-16 |
| JP2013173786A (ja) | 2013-09-05 |
| JP5345381B2 (ja) | 2013-11-20 |
| CA2602324C (en) | 2015-02-24 |
| ZA200709011B (en) | 2009-01-28 |
| SI1866324T1 (sl) | 2010-10-29 |
| DK1866324T3 (da) | 2010-09-27 |
| CN103936807A (zh) | 2014-07-23 |
| EP1866324B1 (en) | 2010-06-16 |
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