JPH0326194B2 - - Google Patents
Info
- Publication number
- JPH0326194B2 JPH0326194B2 JP4781383A JP4781383A JPH0326194B2 JP H0326194 B2 JPH0326194 B2 JP H0326194B2 JP 4781383 A JP4781383 A JP 4781383A JP 4781383 A JP4781383 A JP 4781383A JP H0326194 B2 JPH0326194 B2 JP H0326194B2
- Authority
- JP
- Japan
- Prior art keywords
- carboxamide
- ribofuranosyl
- selenazole
- acyl
- compound
- 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.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 38
- UTYRGKYRIQSXEP-UHFFFAOYSA-N 1,3-selenazole-4-carboxamide Chemical compound NC(=O)C1=C[se]C=N1 UTYRGKYRIQSXEP-UHFFFAOYSA-N 0.000 claims description 24
- 125000002252 acyl group Chemical group 0.000 claims description 22
- -1 R 3 is H Chemical group 0.000 claims description 14
- 150000003857 carboxamides Chemical class 0.000 claims description 10
- 229910019142 PO4 Inorganic materials 0.000 claims description 8
- 239000010452 phosphate Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical class CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 5
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- NAIAADQZBCOAGC-FNCVBFRFSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-3,4-dihydroxyoxolan-2-yl]methyl acetate Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(=O)C)O[C@H]1C1=NC(C(N)=O)=C[se]1 NAIAADQZBCOAGC-FNCVBFRFSA-N 0.000 claims description 4
- WRHDEUYMOACEPD-FNCVBFRFSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] acetate Chemical compound O[C@@H]1[C@H](OC(=O)C)[C@@H](CO)O[C@H]1C1=NC(C(N)=O)=C[se]1 WRHDEUYMOACEPD-FNCVBFRFSA-N 0.000 claims description 4
- CXWUTSUCILFRHS-QCNRFFRDSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] butanoate Chemical compound O[C@@H]1[C@H](OC(=O)CCC)[C@@H](CO)O[C@H]1C1=NC(C(N)=O)=C[se]1 CXWUTSUCILFRHS-QCNRFFRDSA-N 0.000 claims description 4
- KEGKJQRWFNSGII-FNCVBFRFSA-N [(2r,3r,4r,5r)-2-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=NC(C(N)=O)=C[se]1 KEGKJQRWFNSGII-FNCVBFRFSA-N 0.000 claims description 3
- MPCXJTZUURFVQO-QCNRFFRDSA-N [(2r,3r,4r,5r)-2-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl] butanoate Chemical compound CCCC(=O)O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=NC(C(N)=O)=C[se]1 MPCXJTZUURFVQO-QCNRFFRDSA-N 0.000 claims description 3
- MEUDTDPOLBQTGP-QCNRFFRDSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-3,4-dihydroxyoxolan-2-yl]methyl butanoate Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(=O)CCC)O[C@H]1C1=NC(C(N)=O)=C[se]1 MEUDTDPOLBQTGP-QCNRFFRDSA-N 0.000 claims description 3
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 3
- 239000003443 antiviral agent Substances 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 description 43
- 239000000203 mixture Substances 0.000 description 32
- 241001465754 Metazoa Species 0.000 description 31
- 239000000047 product Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 206010028980 Neoplasm Diseases 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 229940125782 compound 2 Drugs 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- CKMBACZHCFMPLQ-DBRKOABJSA-N 2-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3-selenazole-4-carboxamide Chemical class NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=N1 CKMBACZHCFMPLQ-DBRKOABJSA-N 0.000 description 13
- 201000011510 cancer Diseases 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 11
- 230000000840 anti-viral effect Effects 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000006188 syrup Substances 0.000 description 9
- 235000020357 syrup Nutrition 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000006642 detritylation reaction Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- SPVXKVOXSXTJOY-UHFFFAOYSA-N selane Chemical compound [SeH2] SPVXKVOXSXTJOY-UHFFFAOYSA-N 0.000 description 4
- 229910000058 selane Inorganic materials 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000701242 Adenoviridae Species 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 239000004353 Polyethylene glycol 8000 Substances 0.000 description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 3
- 108700010877 adenoviridae proteins Proteins 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 3
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
- AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 2
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 241000450599 DNA viruses Species 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
- 241000700586 Herpesviridae Species 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000711504 Paramyxoviridae Species 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 241000702247 Reoviridae Species 0.000 description 2
- 241000711931 Rhabdoviridae Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- KITFBOYQBYHZMJ-QCNRFFRDSA-N [(2r,3r,4r,5r)-2-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] butanoate Chemical compound CCCC(=O)O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1C1=NC(C(N)=O)=C[se]1 KITFBOYQBYHZMJ-QCNRFFRDSA-N 0.000 description 2
- GXFIQGYGJJDUOA-FDYHWXHSSA-N [(2r,3r,4r,5r)-3,4-diacetyloxy-5-(4-carbamoyl-1,3-selenazol-2-yl)oxolan-2-yl]methyl acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1C1=NC(C(N)=O)=C[se]1 GXFIQGYGJJDUOA-FDYHWXHSSA-N 0.000 description 2
- MERXIJIDHXFRDC-GWOFURMSSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(4-carbamoyl-1,3-selenazol-2-yl)-2-(phosphonooxymethyl)oxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(=O)C)[C@@H](COP(O)(O)=O)O[C@H]1C1=NC(C(N)=O)=C[se]1 MERXIJIDHXFRDC-GWOFURMSSA-N 0.000 description 2
- HXPXOJBOAOKEIA-JUDXGUMMSA-N [(2r,3r,4r,5r)-4-butanoyloxy-5-(4-carbamoyl-1,3-selenazol-2-yl)-2-(phosphonooxymethyl)oxolan-3-yl] butanoate Chemical compound CCCC(=O)O[C@@H]1[C@H](OC(=O)CCC)[C@@H](COP(O)(O)=O)O[C@H]1C1=NC(C(N)=O)=C[se]1 HXPXOJBOAOKEIA-JUDXGUMMSA-N 0.000 description 2
- GCUIHRUSZMITGH-FDYHWXHSSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-2-(phosphonooxymethyl)oxolan-3-yl] benzoate Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](OC(=O)C=3C=CC=CC=3)[C@@H](COP(O)(O)=O)O2)O)=N1 GCUIHRUSZMITGH-FDYHWXHSSA-N 0.000 description 2
- HLUGQLYIPXETOU-QCNRFFRDSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-2-(phosphonooxymethyl)oxolan-3-yl] butanoate Chemical compound O[C@@H]1[C@H](OC(=O)CCC)[C@@H](COP(O)(O)=O)O[C@H]1C1=NC(C(N)=O)=C[se]1 HLUGQLYIPXETOU-QCNRFFRDSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 238000005915 ammonolysis reaction Methods 0.000 description 2
- 159000000032 aromatic acids Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 239000012351 deprotecting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- VJLYHTOSFSGXGH-CQSZACIVSA-N (2R)-1-[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxybenzoyl]pyrrolidine-2-carboxylic acid Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)N2[C@H](CCC2)C(=O)O)C=CC=1 VJLYHTOSFSGXGH-CQSZACIVSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- DYSPLLAJJYBUSY-ZGFBMJKBSA-N 2-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(trityloxymethyl)oxolan-2-yl]-1,3-selenazole-4-carboxamide Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](O)[C@@H](COC(C=3C=CC=CC=3)(C=3C=CC=CC=3)C=3C=CC=CC=3)O2)O)=N1 DYSPLLAJJYBUSY-ZGFBMJKBSA-N 0.000 description 1
- 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 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000007093 Leukemia L1210 Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000005643 Pelargonic acid Substances 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 241000700625 Poxviridae Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- NLZWJHXCWVEBTP-FDYHWXHSSA-N [(2r,3r,4r,5r)-2-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl] benzoate Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)OC(=O)C=2C=CC=CC=2)=N1 NLZWJHXCWVEBTP-FDYHWXHSSA-N 0.000 description 1
- BKOACJKDIXAFRE-FNCVBFRFSA-N [(2r,3r,4r,5r)-2-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1C1=NC(C(N)=O)=C[se]1 BKOACJKDIXAFRE-FNCVBFRFSA-N 0.000 description 1
- ILLOZYTZPKPESX-FDYHWXHSSA-N [(2r,3r,4r,5r)-2-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] benzoate Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(O)=O)O2)OC(=O)C=2C=CC=CC=2)=N1 ILLOZYTZPKPESX-FDYHWXHSSA-N 0.000 description 1
- KRTHXXXHGDWKOJ-GWOFURMSSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(4-carbamoyl-1,3-selenazol-2-yl)-2-(hydroxymethyl)oxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(=O)C)[C@@H](CO)O[C@H]1C1=NC(C(N)=O)=C[se]1 KRTHXXXHGDWKOJ-GWOFURMSSA-N 0.000 description 1
- FQFGOONBOMBXSE-NCXUSEDFSA-N [(2r,3r,4r,5r)-4-benzoyloxy-5-(4-carbamoyl-1,3-selenazol-2-yl)-2-(hydroxymethyl)oxolan-3-yl] benzoate Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](OC(=O)C=3C=CC=CC=3)[C@@H](CO)O2)OC(=O)C=2C=CC=CC=2)=N1 FQFGOONBOMBXSE-NCXUSEDFSA-N 0.000 description 1
- OHLYWSMJYROZDX-JUDXGUMMSA-N [(2r,3r,4r,5r)-4-butanoyloxy-5-(4-carbamoyl-1,3-selenazol-2-yl)-2-(hydroxymethyl)oxolan-3-yl] butanoate Chemical compound CCCC(=O)O[C@@H]1[C@H](OC(=O)CCC)[C@@H](CO)O[C@H]1C1=NC(C(N)=O)=C[se]1 OHLYWSMJYROZDX-JUDXGUMMSA-N 0.000 description 1
- OFMYTVNDIRTGMR-UARRHKHWSA-N [(2r,3r,4s,5s)-3,4-dibenzoyloxy-5-cyanooxolan-2-yl]methyl benzoate Chemical compound O([C@H]1[C@H](C#N)O[C@@H]([C@H]1OC(=O)C=1C=CC=CC=1)COC(=O)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 OFMYTVNDIRTGMR-UARRHKHWSA-N 0.000 description 1
- IDCOLCMQCCCNPZ-FDYHWXHSSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-3,4-dihydroxyoxolan-2-yl]methyl benzoate Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](O)[C@@H](COC(=O)C=3C=CC=CC=3)O2)O)=N1 IDCOLCMQCCCNPZ-FDYHWXHSSA-N 0.000 description 1
- FDFHCIPEQKGCOD-FDYHWXHSSA-N [(2r,3s,4r,5r)-5-(4-carbamoyl-1,3-selenazol-2-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] benzoate Chemical compound NC(=O)C1=C[se]C([C@H]2[C@@H]([C@H](OC(=O)C=3C=CC=CC=3)[C@@H](CO)O2)O)=N1 FDFHCIPEQKGCOD-FDYHWXHSSA-N 0.000 description 1
- WGCOQYDRMPFAMN-ZDUSSCGKSA-N [(3S)-3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-pyrimidin-5-ylmethanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)O[C@@H]1CN(CCC1)C(=O)C=1C=NC=NC=1 WGCOQYDRMPFAMN-ZDUSSCGKSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- NEUSVAOJNUQRTM-UHFFFAOYSA-N cetylpyridinium Chemical compound CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NEUSVAOJNUQRTM-UHFFFAOYSA-N 0.000 description 1
- 229960004830 cetylpyridinium Drugs 0.000 description 1
- RLGQACBPNDBWTB-UHFFFAOYSA-N cetyltrimethylammonium ion Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)C RLGQACBPNDBWTB-UHFFFAOYSA-N 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 125000005131 dialkylammonium group Chemical group 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- IOQPZZOEVPZRBK-UHFFFAOYSA-O octylazanium Chemical compound CCCCCCCC[NH3+] IOQPZZOEVPZRBK-UHFFFAOYSA-O 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 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
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- PAYGMRRPBHYIMA-UHFFFAOYSA-N sodium;trihydrate Chemical compound O.O.O.[Na] PAYGMRRPBHYIMA-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000005866 tritylation reaction Methods 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 230000003253 viricidal effect Effects 0.000 description 1
- 230000001790 virustatic effect Effects 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36096882A | 1982-03-23 | 1982-03-23 | |
| US360968 | 1982-03-23 | ||
| US465221 | 1983-02-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58213765A JPS58213765A (ja) | 1983-12-12 |
| JPH0326194B2 true JPH0326194B2 (fi) | 1991-04-10 |
Family
ID=23420119
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4781383A Granted JPS58213765A (ja) | 1982-03-23 | 1983-03-22 | 新規な２−β−Ｄ−リボフラノシルセレナゾ−ル−４−カルボキサミド化合物およびそれらの製造方法 |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS58213765A (fi) |
| ZA (1) | ZA832003B (fi) |
-
1983
- 1983-03-22 ZA ZA832003A patent/ZA832003B/xx unknown
- 1983-03-22 JP JP4781383A patent/JPS58213765A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58213765A (ja) | 1983-12-12 |
| ZA832003B (en) | 1983-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2155673C (en) | N-alkyl-2-substituted atp analogues | |
| CN102459299A (zh) | N-[(2′r)-2′-脱氧-2′-氟-2′-甲基-p-苯基-5′-尿苷酰基]-l-丙氨酸1-甲基乙基酯及其制备方法 | |
| CN102421293A (zh) | 取代的核苷和核苷酸类似物 | |
| OA12384A (en) | 3'-Prodrugs of 2'-deoxy-beta-l-nucleosides. | |
| JPH0780898B2 (ja) | 抗ウイルスヌクレオシド | |
| JP2002537263A (ja) | 化学物質 | |
| EP3730508A1 (en) | Liver specific delivery-based gemcitabine prodrug nucleoside cyclic phosphate compound, and application thereof | |
| JP2017057200A (ja) | 抗ｄｎａウィルス活性などの生理活性を有するヌクレオシド誘導体 | |
| EP0089678B1 (en) | Novel 2-beta-d-ribofuranosylselenazole-4-carboxamide compounds and methods for their production | |
| JPH0326194B2 (fi) | ||
| US4594414A (en) | 2-β-D-ribofuranosylselenazole-4-carboxamide compounds and methods for their production | |
| US4594416A (en) | 2-β-D-ribofuranosylselenazole-4-carboxamide compounds and methods for their production | |
| KR102619437B1 (ko) | 젬시타빈의 인-함유 프로드러그 | |
| EP0445258B1 (en) | 5'-alkylphosphonylnucleosides as antivirals | |
| CA1175421A (en) | TREATMENT OF MALIGNANT TUMORS WITH 2-.beta.-D- RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE AND RELATED COMPOUNDS | |
| JP2004525136A5 (fi) | ||
| CN109956985A (zh) | 肝递送阿糖胞苷前体药物核苷环磷酸酯化合物及应用 | |
| JP2004525136A (ja) | イノシン化合物及び炎症性疾患もしくは再灌流疾患の治療又は予防のためのその使用 | |
| US5374626A (en) | 5'-alkylphosphonylnucleosides as antivirals | |
| JP2665527B2 (ja) | ２’−デオキシ−２’−メチリデンピリミジンヌクレオチド化合物 | |
| US4680285A (en) | Treatment of malignant tumors with 2-(β-D-ribofuranosylthiazole-4-carboxamide related compounds | |
| WO1991006555A1 (en) | Nucleoside derivative | |
| CA2090026C (en) | Anti-viral compounds and processes for production of anti-viral compounds | |
| JPH0427965B2 (fi) | ||
| JPH0340038B2 (fi) |