SK12442001A3 - Cyklické fosforamidáty, spôsob ich prípravy a farmaceutické kompozície, ktoré ich obsahujú - Google Patents

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Publication number

SK12442001A3

SK12442001A3 SK1244-2001A SK12442001A SK12442001A3 SK 12442001 A3 SK12442001 A3 SK 12442001A3 SK 12442001 A SK12442001 A SK 12442001A SK 12442001 A3 SK12442001 A3 SK 12442001A3

Authority

SK

Slovakia

Prior art keywords

group

aryl

alkyl

atoms

substituted

Prior art date

1999-03-05

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• 238000000034 method Methods 0.000 title claims abstract description 136
• -1 Cyclic phosphoramidates Chemical class 0.000 title claims description 92
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
• 229940002612 prodrug Drugs 0.000 claims abstract description 245
• 239000000651 prodrug Substances 0.000 claims abstract description 245
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 214
• 239000003814 drug Substances 0.000 claims abstract description 179
• 229940079593 drug Drugs 0.000 claims abstract description 175
• 210000004185 liver Anatomy 0.000 claims abstract description 109
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims abstract description 13
• 230000002708 enhancing effect Effects 0.000 claims abstract description 5
• 238000002360 preparation method Methods 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 398
• 229910052721 tungsten Inorganic materials 0.000 claims description 295
• 125000003118 aryl group Chemical group 0.000 claims description 286
• 125000001072 heteroaryl group Chemical group 0.000 claims description 226
• 125000004429 atom Chemical group 0.000 claims description 209
• 229910052739 hydrogen Inorganic materials 0.000 claims description 201
• 239000001257 hydrogen Substances 0.000 claims description 197
• 150000001875 compounds Chemical class 0.000 claims description 177
• 125000005842 heteroatom Chemical group 0.000 claims description 140
• 229910052799 carbon Inorganic materials 0.000 claims description 119
• 229910052698 phosphorus Inorganic materials 0.000 claims description 116
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 115
• 125000002723 alicyclic group Chemical group 0.000 claims description 112
• 125000003107 substituted aryl group Chemical group 0.000 claims description 112
• 229910052720 vanadium Inorganic materials 0.000 claims description 109
• 150000001350 alkyl halides Chemical group 0.000 claims description 107
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 106
• 125000004432 carbon atom Chemical group C* 0.000 claims description 88
• 150000002431 hydrogen Chemical class 0.000 claims description 85
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 79
• 125000004423 acyloxy group Chemical group 0.000 claims description 72
• 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 72
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 70
• 125000002252 acyl group Chemical group 0.000 claims description 69
• 150000001721 carbon Chemical group 0.000 claims description 66
• 230000000694 effects Effects 0.000 claims description 63
• 125000004437 phosphorous atom Chemical group 0.000 claims description 59
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 57
• 239000011574 phosphorus Substances 0.000 claims description 57
• 210000004027 cell Anatomy 0.000 claims description 48
• 239000003112 inhibitor Substances 0.000 claims description 48
• 102000004190 Enzymes Human genes 0.000 claims description 47
• 108090000790 Enzymes Proteins 0.000 claims description 47
• 125000001424 substituent group Chemical group 0.000 claims description 45
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 39
• 229910052717 sulfur Inorganic materials 0.000 claims description 38
• 239000013543 active substance Substances 0.000 claims description 37
• 229910052757 nitrogen Inorganic materials 0.000 claims description 37
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 35
• 125000006413 ring segment Chemical group 0.000 claims description 35
• 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 claims description 34
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 claims description 34
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 34
• 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 33
• 230000001965 increasing effect Effects 0.000 claims description 32
• 101150053185 P450 gene Proteins 0.000 claims description 31
• OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 claims description 31
• 229910019142 PO4 Inorganic materials 0.000 claims description 30
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
• 238000011282 treatment Methods 0.000 claims description 29
• 241001465754 Metazoa Species 0.000 claims description 28
• 206010028980 Neoplasm Diseases 0.000 claims description 27
• 125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 claims description 27
• 239000003795 chemical substances by application Substances 0.000 claims description 25
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 25
• 125000004434 sulfur atom Chemical group 0.000 claims description 25
• OIRDTQYFTABQOQ-UHFFFAOYSA-N ara-adenosine Natural products Nc1ncnc2n(cnc12)C1OC(CO)C(O)C1O OIRDTQYFTABQOQ-UHFFFAOYSA-N 0.000 claims description 24
• 101150035354 araA gene Proteins 0.000 claims description 24
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 23
• ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 23
• 125000005750 substituted cyclic group Chemical group 0.000 claims description 23
• 231100000419 toxicity Toxicity 0.000 claims description 23
• 230000001988 toxicity Effects 0.000 claims description 23
• WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims description 19
• 201000011510 cancer Diseases 0.000 claims description 19
• 239000010452 phosphate Substances 0.000 claims description 19
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical class ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 18
• 238000006243 chemical reaction Methods 0.000 claims description 18
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 17
• 150000004712 monophosphates Chemical class 0.000 claims description 17
• 101100002068 Bacillus subtilis (strain 168) araR gene Proteins 0.000 claims description 16
• 101150044616 araC gene Proteins 0.000 claims description 16
• 230000026731 phosphorylation Effects 0.000 claims description 16
• 238000006366 phosphorylation reaction Methods 0.000 claims description 16
• 230000008569 process Effects 0.000 claims description 16
• 235000000346 sugar Nutrition 0.000 claims description 16
• JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 claims description 15
• 108091000080 Phosphotransferase Proteins 0.000 claims description 14
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 14
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 14
• 150000002148 esters Chemical class 0.000 claims description 14
• 229910052760 oxygen Inorganic materials 0.000 claims description 14
• 230000003285 pharmacodynamic effect Effects 0.000 claims description 14
• 102000020233 phosphotransferase Human genes 0.000 claims description 14
• 108090000623 proteins and genes Proteins 0.000 claims description 14
• 231100001274 therapeutic index Toxicity 0.000 claims description 14
• 239000002246 antineoplastic agent Substances 0.000 claims description 13
• 201000010099 disease Diseases 0.000 claims description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 208000006454 hepatitis Diseases 0.000 claims description 13
• 231100000283 hepatitis Toxicity 0.000 claims description 13
• 230000001976 improved effect Effects 0.000 claims description 13
• 229960000329 ribavirin Drugs 0.000 claims description 13
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 13
• 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 12
• 206010012601 diabetes mellitus Diseases 0.000 claims description 12
• IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 12
• 239000001301 oxygen Substances 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 239000001226 triphosphate Substances 0.000 claims description 12
• UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 12
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims description 11
• RLAHNGKRJJEIJL-RFZPGFLSSA-N [(2r,4r)-4-(2,6-diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@H]1CO[C@@H](CO)O1 RLAHNGKRJJEIJL-RFZPGFLSSA-N 0.000 claims description 11
• FRPXSOOHWNMLPH-LURJTMIESA-N [(2s)-1-(6-aminopurin-9-yl)-3-hydroxypropan-2-yl]oxymethylphosphonic acid Chemical compound NC1=NC=NC2=C1N=CN2C[C@@H](CO)OCP(O)(O)=O FRPXSOOHWNMLPH-LURJTMIESA-N 0.000 claims description 11
• 239000003443 antiviral agent Substances 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 229960001179 penciclovir Drugs 0.000 claims description 11
• VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims description 11
• 235000011178 triphosphate Nutrition 0.000 claims description 11
• HBUBKKRHXORPQB-FJFJXFQQSA-N (2R,3S,4S,5R)-2-(6-amino-2-fluoro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O HBUBKKRHXORPQB-FJFJXFQQSA-N 0.000 claims description 10
• XHXFQGAZAVKMFF-UHFFFAOYSA-N 2-(2,6-diaminopurin-9-yl)ethoxymethylphosphonic acid Chemical compound NC1=NC(N)=C2N=CN(CCOCP(O)(O)=O)C2=N1 XHXFQGAZAVKMFF-UHFFFAOYSA-N 0.000 claims description 10
• BYEIJZFKOAXBBV-ATZCPNFKSA-N N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine Chemical compound CC(C)[C@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)CCC[C@H](N)C(O)=O BYEIJZFKOAXBBV-ATZCPNFKSA-N 0.000 claims description 10
• 208000036142 Viral infection Diseases 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• QOVUZUCXPAZXDZ-RXMQYKEDSA-N 2-amino-9-[(3r)-3,4-dihydroxybutyl]-3h-purin-6-one Chemical compound O=C1NC(N)=NC2=C1N=CN2CC[C@@H](O)CO QOVUZUCXPAZXDZ-RXMQYKEDSA-N 0.000 claims description 9
• VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 claims description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
• 150000002367 halogens Chemical class 0.000 claims description 9
• 210000003734 kidney Anatomy 0.000 claims description 9
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 9
• 239000011593 sulfur Substances 0.000 claims description 9
• 230000009385 viral infection Effects 0.000 claims description 9
• BCSLVBZWCFTDPK-UDJQAZALSA-N 2-amino-9-[(2r,3r,4s)-3,4-bis(hydroxymethyl)oxetan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@H]1CO BCSLVBZWCFTDPK-UDJQAZALSA-N 0.000 claims description 8
• SWFJAJRDLUUIOA-IBCQBUCCSA-N 5-ethyl-1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(CC)=CN1[C@H]1[C@@H](F)[C@H](O)[C@@H](CO)O1 SWFJAJRDLUUIOA-IBCQBUCCSA-N 0.000 claims description 8
• VZKXOWRNJDEGLZ-WHFBIAKZSA-N Cys-Asp-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O VZKXOWRNJDEGLZ-WHFBIAKZSA-N 0.000 claims description 8
• PYJIWOQTJHPDAK-PRJMDXOYSA-N [(1s,2r,3s)-3-(6-aminopurin-9-yl)-2-(hydroxymethyl)cyclobutyl]methanol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](CO)[C@H]1CO PYJIWOQTJHPDAK-PRJMDXOYSA-N 0.000 claims description 8
• BFZJTDBFUROXJA-UHFFFAOYSA-N [1-(6-aminopurin-9-yl)-3-fluoropropan-2-yl]oxymethylphosphonic acid Chemical compound NC1=NC=NC2=C1N=CN2CC(CF)OCP(O)(O)=O BFZJTDBFUROXJA-UHFFFAOYSA-N 0.000 claims description 8
• 239000002253 acid Substances 0.000 claims description 8
• 229960002756 azacitidine Drugs 0.000 claims description 8
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
• 208000019423 liver disease Diseases 0.000 claims description 8
• 230000001225 therapeutic effect Effects 0.000 claims description 8
• 230000003612 virological effect Effects 0.000 claims description 8
• IPVFGAYTKQKGBM-BYPJNBLXSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound F[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 IPVFGAYTKQKGBM-BYPJNBLXSA-N 0.000 claims description 7
• GIMSJJHKKXRFGV-BYPJNBLXSA-N 4-amino-1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidin-2-one Chemical compound C1=C(I)C(N)=NC(=O)N1[C@H]1[C@@H](F)[C@H](O)[C@@H](CO)O1 GIMSJJHKKXRFGV-BYPJNBLXSA-N 0.000 claims description 7
• QBEIABZPRBJOFU-VDTYLAMSSA-N 4-amino-5-fluoro-1-[(2s,5r)-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)CC1 QBEIABZPRBJOFU-VDTYLAMSSA-N 0.000 claims description 7
• GSDZMZKDKWSUOV-OEJXEDHQSA-N 5-prop-1-ynyl-1-[(3S,4R,5R)-3,4,5-trihydroxyoxan-2-yl]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CC)=CN1C1[C@@H](O)[C@H](O)[C@H](O)CO1 GSDZMZKDKWSUOV-OEJXEDHQSA-N 0.000 claims description 7
• YOOVTUPUBVHMPG-UHFFFAOYSA-N Coformycin Natural products OC1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 YOOVTUPUBVHMPG-UHFFFAOYSA-N 0.000 claims description 7
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 7
• 230000000840 anti-viral effect Effects 0.000 claims description 7
• YOOVTUPUBVHMPG-LODYRLCVSA-O coformycin(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C([NH+]=CNC[C@H]2O)=C2N=C1 YOOVTUPUBVHMPG-LODYRLCVSA-O 0.000 claims description 7
• 229940104302 cytosine Drugs 0.000 claims description 7
• 210000003494 hepatocyte Anatomy 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• LMJVXGOFWKVXAW-OXOINMOOSA-N oxetanocin A Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@H]1CO LMJVXGOFWKVXAW-OXOINMOOSA-N 0.000 claims description 7
• 230000002829 reductive effect Effects 0.000 claims description 7
• JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 claims description 7
• 229960001225 rifampicin Drugs 0.000 claims description 7
• 210000004881 tumor cell Anatomy 0.000 claims description 7
• YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 claims description 6
• YKBGVTZYEHREMT-UHFFFAOYSA-N 2'-deoxyguanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 claims description 6
• HSBKFSPNDWWPSL-VDTYLAMSSA-N 4-amino-5-fluoro-1-[(2s,5r)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1C=C[C@H](CO)O1 HSBKFSPNDWWPSL-VDTYLAMSSA-N 0.000 claims description 6
• NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 claims description 6
• XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 claims description 6
• NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 6
• WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 claims description 6
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• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
• 125000000328 arabinofuranosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 6
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 6
• 229950004398 broxuridine Drugs 0.000 claims description 6
• 239000007795 chemical reaction product Substances 0.000 claims description 6
• GBBJCSTXCAQSSJ-XQXXSGGOSA-N clevudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1[C@H](F)[C@@H](O)[C@H](CO)O1 GBBJCSTXCAQSSJ-XQXXSGGOSA-N 0.000 claims description 6
• VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 claims description 6
• 239000002359 drug metabolite Substances 0.000 claims description 6
• 239000008103 glucose Substances 0.000 claims description 6
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 claims description 6
• ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 6
• GHTIVOZHSNRAAW-JZXVYGCJSA-N (1E)-1-(4-hydroxybut-2-enylidene)-4-iminopyrimidin-1-ium-2-olate Chemical compound OCC=C\C=[N+]1/C=CC(=N)N=C1[O-] GHTIVOZHSNRAAW-JZXVYGCJSA-N 0.000 claims description 5
• GBBJCSTXCAQSSJ-JVZYCSMKSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@@H](F)[C@H](O)[C@@H](CO)O1 GBBJCSTXCAQSSJ-JVZYCSMKSA-N 0.000 claims description 5
• 208000030852 Parasitic disease Diseases 0.000 claims description 5
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