KR20080021797A - 플라비바이러스 및 페스티바이러스의 치료방법 및 조성물 - Google Patents
플라비바이러스 및 페스티바이러스의 치료방법 및 조성물 Download PDFInfo
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- KR20080021797A KR20080021797A KR1020087001618A KR20087001618A KR20080021797A KR 20080021797 A KR20080021797 A KR 20080021797A KR 1020087001618 A KR1020087001618 A KR 1020087001618A KR 20087001618 A KR20087001618 A KR 20087001618A KR 20080021797 A KR20080021797 A KR 20080021797A
- Authority
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- South Korea
- Prior art keywords
- alkyl
- acyl
- independently
- compound
- pharmaceutically acceptable
- 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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- 241000710831 Flavivirus Species 0.000 title claims abstract description 58
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- 238000011282 treatment Methods 0.000 title claims description 22
- 238000000034 method Methods 0.000 title abstract description 67
- 241000710778 Pestivirus Species 0.000 title abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 128
- 125000000217 alkyl group Chemical group 0.000 claims description 641
- 125000002252 acyl group Chemical group 0.000 claims description 280
- 150000001875 compounds Chemical class 0.000 claims description 271
- 229910019142 PO4 Inorganic materials 0.000 claims description 211
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 165
- 239000010452 phosphate Chemical group 0.000 claims description 164
- 229910052739 hydrogen Inorganic materials 0.000 claims description 162
- 239000001257 hydrogen Substances 0.000 claims description 159
- -1 bromo, chloro, fluoro, iodo Chemical group 0.000 claims description 148
- 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 130
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 121
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 107
- 125000003342 alkenyl group Chemical group 0.000 claims description 103
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 94
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 87
- 150000002632 lipids Chemical group 0.000 claims description 81
- 125000000304 alkynyl group Chemical group 0.000 claims description 73
- 229910004013 NO 2 Inorganic materials 0.000 claims description 70
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 70
- 229920002554 vinyl polymer Polymers 0.000 claims description 70
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
- 125000001424 substituent group Chemical group 0.000 claims description 68
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 67
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 66
- 238000001727 in vivo Methods 0.000 claims description 66
- 239000001226 triphosphate Substances 0.000 claims description 66
- 235000011178 triphosphate Nutrition 0.000 claims description 66
- 150000001720 carbohydrates Chemical class 0.000 claims description 65
- 235000014633 carbohydrates Nutrition 0.000 claims description 65
- 235000012000 cholesterol Nutrition 0.000 claims description 65
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 65
- 150000003904 phospholipids Chemical class 0.000 claims description 65
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 claims description 65
- 150000001413 amino acids Chemical class 0.000 claims description 64
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 64
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 64
- 239000000460 chlorine Substances 0.000 claims description 62
- 229910052794 bromium Inorganic materials 0.000 claims description 58
- 229910052801 chlorine Inorganic materials 0.000 claims description 58
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 56
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 56
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 56
- 125000003282 alkyl amino group Chemical group 0.000 claims description 55
- 230000000840 anti-viral effect Effects 0.000 claims description 51
- 229910052760 oxygen Inorganic materials 0.000 claims description 50
- 229910005965 SO 2 Inorganic materials 0.000 claims description 47
- 229910052717 sulfur Inorganic materials 0.000 claims description 47
- 239000003814 drug Substances 0.000 claims description 37
- 208000004571 Pestivirus Infections Diseases 0.000 claims description 32
- 206010054261 Flavivirus infection Diseases 0.000 claims description 30
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
- 229910052740 iodine Inorganic materials 0.000 claims description 30
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 28
- 239000011630 iodine Substances 0.000 claims description 28
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 15
- 125000001769 aryl amino group Chemical group 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000004104 aryloxy group Chemical group 0.000 claims description 14
- LBQAJLBSGOBDQF-UHFFFAOYSA-N nitro azanylidynemethanesulfonate Chemical compound [O-][N+](=O)OS(=O)(=O)C#N LBQAJLBSGOBDQF-UHFFFAOYSA-N 0.000 claims description 14
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical group [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 14
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 14
- 238000009472 formulation Methods 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 3
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 claims 12
- 125000001246 bromo group Chemical group Br* 0.000 claims 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims 4
- 125000002346 iodo group Chemical group I* 0.000 claims 4
- 238000011321 prophylaxis Methods 0.000 claims 3
- 229940002612 prodrug Drugs 0.000 abstract description 155
- 239000000651 prodrug Substances 0.000 abstract description 155
- 239000002777 nucleoside Substances 0.000 abstract description 94
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 19
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 235000021317 phosphate Nutrition 0.000 description 187
- 239000002585 base Substances 0.000 description 126
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 80
- 125000003118 aryl group Chemical group 0.000 description 61
- 150000002431 hydrogen Chemical group 0.000 description 61
- 125000003835 nucleoside group Chemical group 0.000 description 60
- 150000003871 sulfonates Chemical group 0.000 description 53
- 229940024606 amino acid Drugs 0.000 description 52
- 239000001177 diphosphate Substances 0.000 description 48
- 235000011180 diphosphates Nutrition 0.000 description 48
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 47
- 150000004712 monophosphates Chemical class 0.000 description 47
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 47
- 235000000346 sugar Nutrition 0.000 description 46
- 210000004027 cell Anatomy 0.000 description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 42
- 150000008163 sugars Chemical class 0.000 description 37
- 230000009467 reduction Effects 0.000 description 34
- 238000003786 synthesis reaction Methods 0.000 description 32
- 229930024421 Adenine Natural products 0.000 description 27
- 229960000643 adenine Drugs 0.000 description 27
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 27
- 125000006239 protecting group Chemical group 0.000 description 27
- 241000700605 Viruses Species 0.000 description 23
- 239000003112 inhibitor Substances 0.000 description 21
- 239000002342 ribonucleoside Substances 0.000 description 20
- 241000710780 Bovine viral diarrhea virus 1 Species 0.000 description 18
- 125000003729 nucleotide group Chemical group 0.000 description 18
- 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 description 16
- 238000004458 analytical method Methods 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000002773 nucleotide Substances 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 229960000329 ribavirin Drugs 0.000 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 description 13
- 208000005176 Hepatitis C Diseases 0.000 description 12
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- 238000003556 assay Methods 0.000 description 11
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- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 241000282693 Cercopithecidae Species 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
- 239000007800 oxidant agent Substances 0.000 description 8
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
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- 238000002512 chemotherapy Methods 0.000 description 7
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- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
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- 239000001963 growth medium Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
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- 230000005764 inhibitory process Effects 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
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- 241000282567 Macaca fascicularis Species 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
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- 238000007429 general method Methods 0.000 description 5
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- 150000002596 lactones Chemical class 0.000 description 5
- 230000001590 oxidative effect Effects 0.000 description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 5
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 4
- 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 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241000710777 Classical swine fever virus Species 0.000 description 4
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 4
- 239000005751 Copper oxide Substances 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- 229910004373 HOAc Inorganic materials 0.000 description 4
- 239000003810 Jones reagent Substances 0.000 description 4
- 239000002841 Lewis acid Substances 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- 229910019093 NaOCl Inorganic materials 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 4
- 239000011609 ammonium molybdate Substances 0.000 description 4
- 229940010552 ammonium molybdate Drugs 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 4
- 229910000431 copper oxide Inorganic materials 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 229940104302 cytosine Drugs 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
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- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 4
- 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 4
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- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 4
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- 125000001979 organolithium group Chemical group 0.000 description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
- 239000003444 phase transfer catalyst Substances 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000012286 potassium permanganate Substances 0.000 description 4
- 239000003586 protic polar solvent Substances 0.000 description 4
- 229910052707 ruthenium Inorganic materials 0.000 description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229940113082 thymine Drugs 0.000 description 4
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 4
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 4
- 229940035893 uracil Drugs 0.000 description 4
- ZZKNRXZVGOYGJT-VKHMYHEASA-N (2s)-2-[(2-phosphonoacetyl)amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CP(O)(O)=O ZZKNRXZVGOYGJT-VKHMYHEASA-N 0.000 description 3
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- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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