CA2224165A1 - 9-(2-deoxy-2-fluoro-4-thio-.beta.-d-arabinofuranosyl)purine derivatives - Google Patents
9-(2-deoxy-2-fluoro-4-thio-.beta.-d-arabinofuranosyl)purine derivatives Download PDFInfo
- Publication number
- CA2224165A1 CA2224165A1 CA002224165A CA2224165A CA2224165A1 CA 2224165 A1 CA2224165 A1 CA 2224165A1 CA 002224165 A CA002224165 A CA 002224165A CA 2224165 A CA2224165 A CA 2224165A CA 2224165 A1 CA2224165 A1 CA 2224165A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- fluoro
- group
- deoxy
- 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.)
- Abandoned
Links
- -1 hydroxy, hydroxyamino, aminoxy Chemical group 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 34
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- 125000000262 haloalkenyl group Chemical group 0.000 claims abstract description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 7
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 158
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 125000006239 protecting group Chemical group 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 239000002585 base Substances 0.000 claims description 26
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 17
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 16
- VNGHQEIJKGMIPH-IBCQBUCCSA-N (2r,3s,4s,5r)-4-fluoro-2-(hydroxymethyl)-5-purin-9-ylthiolan-3-ol Chemical class F[C@H]1[C@H](O)[C@@H](CO)S[C@H]1N1C2=NC=NC=C2N=C1 VNGHQEIJKGMIPH-IBCQBUCCSA-N 0.000 claims description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- 230000000865 phosphorylative effect Effects 0.000 claims description 10
- 150000008065 acid anhydrides Chemical class 0.000 claims description 9
- 238000006206 glycosylation reaction Methods 0.000 claims description 9
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 9
- 239000012434 nucleophilic reagent Substances 0.000 claims description 9
- 230000002633 protecting effect Effects 0.000 claims description 9
- 150000003462 sulfoxides Chemical class 0.000 claims description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 6
- XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical compound N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000006735 epoxidation reaction Methods 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- FUGLMDHVQLKYJO-GQTRHBFLSA-N (2r,3s,4s,5r)-5-(6-aminopurin-9-yl)-4-fluoro-2-(hydroxymethyl)thiolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1S[C@H](CO)[C@@H](O)[C@@H]1F FUGLMDHVQLKYJO-GQTRHBFLSA-N 0.000 claims description 4
- 238000006778 Pummerer Sulfoxide rearrangement reaction Methods 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- CHJNRPSUWOMJIA-AYQXTPAHSA-N (2r,3s,4s,5r)-5-(2,6-diaminopurin-9-yl)-4-fluoro-2-(hydroxymethyl)thiolan-3-ol Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@@H]1S[C@H](CO)[C@@H](O)[C@@H]1F CHJNRPSUWOMJIA-AYQXTPAHSA-N 0.000 claims description 3
- BLRVRSGSWBOLRH-AYQXTPAHSA-N (2r,3s,4s,5r)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)thiolan-3-ol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1S[C@H](CO)[C@@H](O)[C@@H]1F BLRVRSGSWBOLRH-AYQXTPAHSA-N 0.000 claims description 3
- CFNVWWATCWIRKR-AYQXTPAHSA-N (2r,3s,4s,5r)-5-(6-amino-2-fluoropurin-9-yl)-4-fluoro-2-(hydroxymethyl)thiolan-3-ol Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1S[C@H](CO)[C@@H](O)[C@@H]1F CFNVWWATCWIRKR-AYQXTPAHSA-N 0.000 claims description 3
- ICRDSLKBARULFR-AYQXTPAHSA-N 2-amino-9-[(2r,3s,4s,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)thiolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1S[C@H](CO)[C@@H](O)[C@@H]1F ICRDSLKBARULFR-AYQXTPAHSA-N 0.000 claims description 3
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 239000011968 lewis acid catalyst Substances 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000001730 thiiranyl group Chemical group 0.000 claims description 3
- 239000003443 antiviral agent Substances 0.000 claims description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 17
- 230000000840 anti-viral effect Effects 0.000 abstract description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 abstract description 3
- 239000001257 hydrogen Substances 0.000 abstract description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 abstract 1
- 150000003212 purines Chemical class 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 76
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- 239000002904 solvent Substances 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 229910001868 water Inorganic materials 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 20
- 229940073584 methylene chloride Drugs 0.000 description 20
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 19
- 229940093499 ethyl acetate Drugs 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 239000012044 organic layer Substances 0.000 description 19
- 238000010898 silica gel chromatography Methods 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 229910052786 argon Inorganic materials 0.000 description 14
- 229960001701 chloroform Drugs 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 13
- 235000002639 sodium chloride Nutrition 0.000 description 13
- 235000019441 ethanol Nutrition 0.000 description 12
- 238000007796 conventional method Methods 0.000 description 11
- 238000002955 isolation Methods 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- 230000007505 plaque formation Effects 0.000 description 9
- 239000007832 Na2SO4 Substances 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
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- 230000005764 inhibitory process Effects 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
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- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 5
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- 239000003513 alkali Substances 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 5
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 4
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 4
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 4
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- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
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- 239000000969 carrier Substances 0.000 description 4
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
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- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
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- AXMOZGKEVIBBCF-UHFFFAOYSA-M lithium;propanoate Chemical compound [Li+].CCC([O-])=O AXMOZGKEVIBBCF-UHFFFAOYSA-M 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
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- ZURGFCUYILNMNA-UHFFFAOYSA-N n-(7h-purin-6-yl)acetamide Chemical compound CC(=O)NC1=NC=NC2=C1NC=N2 ZURGFCUYILNMNA-UHFFFAOYSA-N 0.000 description 1
- HYZHKBPZFYNYNH-UHFFFAOYSA-N n-(trifluoromethyl)-7h-purin-6-amine Chemical compound FC(F)(F)NC1=NC=NC2=C1NC=N2 HYZHKBPZFYNYNH-UHFFFAOYSA-N 0.000 description 1
- UQELSLLOPRNRNF-UHFFFAOYSA-N o-(7h-purin-6-yl)hydroxylamine Chemical compound NOC1=NC=NC2=C1NC=N2 UQELSLLOPRNRNF-UHFFFAOYSA-N 0.000 description 1
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- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- BWILYWWHXDGKQA-UHFFFAOYSA-M potassium propanoate Chemical compound [K+].CCC([O-])=O BWILYWWHXDGKQA-UHFFFAOYSA-M 0.000 description 1
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- CUNPJFGIODEJLQ-UHFFFAOYSA-M potassium;2,2,2-trifluoroacetate Chemical compound [K+].[O-]C(=O)C(F)(F)F CUNPJFGIODEJLQ-UHFFFAOYSA-M 0.000 description 1
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- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
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- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- 239000002718 pyrimidine nucleoside Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- UYCAUPASBSROMS-AWQJXPNKSA-M sodium;2,2,2-trifluoroacetate Chemical compound [Na+].[O-][13C](=O)[13C](F)(F)F UYCAUPASBSROMS-AWQJXPNKSA-M 0.000 description 1
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- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- SINOBGPHNIFPGE-NWIRRVQCSA-N tert-butyl-[[(2r,3s,4s)-5-(2,6-dichloropurin-9-yl)-4-fluoro-3-phenylmethoxythiolan-2-yl]methoxy]-diphenylsilane Chemical compound O([C@H]1[C@H](F)C(S[C@@H]1CO[Si](C(C)(C)C)(C=1C=CC=CC=1)C=1C=CC=CC=1)N1C2=NC(Cl)=NC(Cl)=C2N=C1)CC1=CC=CC=C1 SINOBGPHNIFPGE-NWIRRVQCSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 239000005450 thionucleoside Substances 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
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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
- C07H19/06—Pyrimidine radicals
-
- 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
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11196896 | 1996-04-09 | ||
| JP111968/1996 | 1996-04-09 | ||
| JP215083/1996 | 1996-07-26 | ||
| JP21508396 | 1996-07-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2224165A1 true CA2224165A1 (en) | 1997-10-16 |
Family
ID=26451223
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002224165A Abandoned CA2224165A1 (en) | 1996-04-09 | 1997-04-09 | 9-(2-deoxy-2-fluoro-4-thio-.beta.-d-arabinofuranosyl)purine derivatives |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US6103707A (cg-RX-API-DMAC10.html) |
| EP (1) | EP0839813A1 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2224165A1 (cg-RX-API-DMAC10.html) |
| WO (1) | WO1997037993A1 (cg-RX-API-DMAC10.html) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP1754710A3 (en) * | 1998-02-25 | 2007-12-19 | Emory University | 2'-Fluoroncucleosides |
| MXPA00008348A (es) * | 1998-02-25 | 2005-07-15 | Univ Emory | 2-fluronucleosidos. |
| KR100886653B1 (ko) | 1998-02-25 | 2009-03-04 | 에모리 유니버시티 | 2'-플루오로뉴클레오사이드 |
| US6124463A (en) * | 1998-07-02 | 2000-09-26 | Dupont Pharmaceuticals | Benzimidazoles as corticotropin release factor antagonists |
| US6365589B1 (en) | 1998-07-02 | 2002-04-02 | Bristol-Myers Squibb Pharma Company | Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists |
| JP5379347B2 (ja) * | 2003-09-18 | 2013-12-25 | アイシス ファーマシューティカルズ， インコーポレーテッド | ４’−チオヌクレオシドおよびオリゴマー化合物 |
| BR112012014490B1 (pt) | 2009-12-18 | 2021-07-13 | Libramedicina, Inc | Processos para a preparação de 1-o-acil-2-desóxi-2-fluoro-4-tio-?-d-arabinofuranoses e compostos intermediários dos mesmos |
| NZ701245A (en) | 2012-03-28 | 2015-12-24 | Fujifilm Corp | Salt of 1-(2-deoxy-2-fluoro-4-thio-β-d-arabinofuranosyl)cytosine |
| EP2883866B1 (en) | 2012-08-13 | 2019-02-27 | FUJIFILM Corporation | INTERMEDIATE FOR SYNTHESIS OF 1-(2-DEOXY-2-FLUORO-4-THIO-beta-D-ARABINOFURANOSYL) CYTOSINE, INTERMEDIATE FOR SYNTHESIS OF THIONUCLEOSIDE, AND METHODS FOR PRODUCING THESE INTERMEDIATES |
| WO2015125781A1 (ja) | 2014-02-18 | 2015-08-27 | 富士フイルム株式会社 | チオラン骨格型糖化合物の製造方法およびチオラン骨格型糖化合物 |
| JP6204223B2 (ja) | 2014-02-19 | 2017-09-27 | 富士フイルム株式会社 | チオピラノース化合物等の製造方法 |
| TWI678373B (zh) | 2014-10-31 | 2019-12-01 | 日商富士軟片股份有限公司 | 硫代核苷衍生物或其鹽及醫藥組合物 |
| CA2971382C (en) * | 2014-11-07 | 2023-03-07 | The Asan Foundation | Method for preparing organic fluoride-aliphatic compound and method for purifying organic fluoride-aliphatic compound |
| KR102198656B1 (ko) | 2016-08-31 | 2021-01-05 | 후지필름 가부시키가이샤 | 항종양제, 항종양 효과 증강제 및 항종양용 키트 |
| CA3089728C (en) | 2018-01-29 | 2023-01-10 | Fujifilm Corporation | Antitumor agent for biliary tract cancer and method for treating biliary tract cancer |
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|---|---|---|---|---|
| IE74701B1 (en) * | 1989-10-04 | 1997-07-30 | Univ Birmingham | Further antiviral pyrimidine nucleosides |
| JPH03264582A (ja) * | 1990-03-13 | 1991-11-25 | Noguchi Kenkyusho | ２’，３’―ジデオキシ―２’，３’―ジ置換―ヌクレオシド類とその製造方法 |
| US5128458A (en) * | 1990-04-20 | 1992-07-07 | Southern Research Institute | 2',3'-dideoxy-4'-thioribonucleosides as antiviral agents |
| CA2139132A1 (en) * | 1992-07-02 | 1994-01-20 | George W. Koszalka | Therapeutic nucleosides |
| EP0630897A3 (en) * | 1993-06-25 | 1995-03-01 | Bristol Myers Squibb Co | 3-hydroxy-4-hydroxymethyl-2-methylene-cyclopentyl purines and pyrimidines. |
| EP0679657B1 (de) * | 1994-04-27 | 2003-07-09 | Novartis AG | Nukleoside und Oligonukleotide mit 2'-Ethergruppen |
-
1997
- 1997-04-09 CA CA002224165A patent/CA2224165A1/en not_active Abandoned
- 1997-04-09 WO PCT/JP1997/001205 patent/WO1997037993A1/ja not_active Ceased
- 1997-04-09 US US08/973,530 patent/US6103707A/en not_active Expired - Fee Related
- 1997-04-09 EP EP97916632A patent/EP0839813A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0839813A4 (cg-RX-API-DMAC10.html) | 1998-05-06 |
| EP0839813A1 (en) | 1998-05-06 |
| US6103707A (en) | 2000-08-15 |
| WO1997037993A1 (en) | 1997-10-16 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
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