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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- 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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- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 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
- 239000004300 potassium benzoate Substances 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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- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
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- 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
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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 (enExample) |
| EP (1) | EP0839813A1 (enExample) |
| CA (1) | CA2224165A1 (enExample) |
| WO (1) | WO1997037993A1 (enExample) |
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| IL138037A0 (en) * | 1998-02-25 | 2001-10-31 | Univ Emory | 2'-fluoronucleosides |
| KR100886653B1 (ko) | 1998-02-25 | 2009-03-04 | 에모리 유니버시티 | 2'-플루오로뉴클레오사이드 |
| EP1754710A3 (en) * | 1998-02-25 | 2007-12-19 | Emory University | 2'-Fluoroncucleosides |
| US6365589B1 (en) | 1998-07-02 | 2002-04-02 | Bristol-Myers Squibb Pharma Company | Imidazo-pyridines, -pyridazines, and -triazines as corticotropin releasing factor antagonists |
| US6124463A (en) * | 1998-07-02 | 2000-09-26 | Dupont Pharmaceuticals | Benzimidazoles as corticotropin release factor antagonists |
| WO2005027962A1 (en) * | 2003-09-18 | 2005-03-31 | Isis Pharmaceuticals, Inc. | 4’-thionucleosides and oligomeric compounds |
| KR101814549B1 (ko) | 2009-12-18 | 2018-01-04 | 가부시키가이샤 리브라메디시나 | 치환 1-Ｏ-아실-2-데옥시-2-플루오로-4-티오-β-Ｄ-아라비노푸라노스의 제조방법 |
| CN104203969B (zh) | 2012-03-28 | 2016-08-31 | 富士胶片株式会社 | 1-(2-脱氧-2-氟-4-硫代-β-D-阿拉伯呋喃糖基)胞嘧啶的盐 |
| CN107011168B (zh) | 2012-08-13 | 2020-06-09 | 富士胶片株式会社 | 胞嘧啶类的合成中间体和硫代核苷的合成中间体 |
| CN106061959B (zh) | 2014-02-18 | 2018-11-09 | 富士胶片株式会社 | 四氢噻吩骨架型糖化合物的制造方法及四氢噻吩骨架型糖化合物 |
| 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 |
| RU2710558C2 (ru) * | 2014-11-07 | 2019-12-27 | Дзе Асан Фаундейшн | Способ получения фторзамещенного органического алифатического соединения и способ очистки фторзамещенного органического алифатического соединения |
| AU2017319260B2 (en) | 2016-08-31 | 2020-01-30 | Fujifilm Corporation | Anti-tumor agent, anti-tumor effect enhancer, and anti-tumor kit |
| WO2019146130A1 (ja) | 2018-01-29 | 2019-08-01 | 富士フイルム株式会社 | 胆道がん用抗腫瘍剤および胆道がんの処置方法 |
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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. |
| ES2203635T3 (es) * | 1994-04-27 | 2004-04-16 | Novartis Ag | Nucleosidos y oligonucleotidos con grupos 2'-eter. |
-
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 EP EP97916632A patent/EP0839813A1/en not_active Withdrawn
- 1997-04-09 US US08/973,530 patent/US6103707A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0839813A1 (en) | 1998-05-06 |
| WO1997037993A1 (en) | 1997-10-16 |
| EP0839813A4 (enExample) | 1998-05-06 |
| US6103707A (en) | 2000-08-15 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Dead |