DE2220246A1 - 1,2,4 Tnazol Nukleoside - Google Patents
1,2,4 Tnazol NukleosideInfo
- Publication number
- DE2220246A1 DE2220246A1 DE19722220246 DE2220246A DE2220246A1 DE 2220246 A1 DE2220246 A1 DE 2220246A1 DE 19722220246 DE19722220246 DE 19722220246 DE 2220246 A DE2220246 A DE 2220246A DE 2220246 A1 DE2220246 A1 DE 2220246A1
- Authority
- DE
- Germany
- Prior art keywords
- triazole
- compound
- ribofuranosyl
- phosphate
- carboxamide
- 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.)
- Withdrawn
Links
- 239000002777 nucleoside Substances 0.000 title description 14
- 125000003835 nucleoside group Chemical group 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims description 40
- 229910019142 PO4 Inorganic materials 0.000 claims description 32
- 239000010452 phosphate Substances 0.000 claims description 20
- 235000021317 phosphate Nutrition 0.000 claims description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 10
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 150000003863 ammonium salts Chemical class 0.000 claims description 7
- 150000001447 alkali salts Chemical class 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- UQSPFUMMCXCDLF-AFCXAGJDSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carbothioamide Chemical compound N1=C(C(=S)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UQSPFUMMCXCDLF-AFCXAGJDSA-N 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 230000017105 transposition Effects 0.000 claims description 3
- UZAZHIXEGDBPKD-TXICZTDVSA-N 5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-1,2,4-triazole-3-carboxamide Chemical compound N1C(C(=O)N)=NC([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=N1 UZAZHIXEGDBPKD-TXICZTDVSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- IWUCXVSUMQZMFG-GUMKFJOWSA-N 1-[(2r,3r,4r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-GUMKFJOWSA-N 0.000 claims 1
- PIGYMBULXKLTCJ-UHSSARMYSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboximidamide;hydrochloride Chemical compound Cl.N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 PIGYMBULXKLTCJ-UHSSARMYSA-N 0.000 claims 1
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 19
- 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
- 238000004458 analytical method Methods 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 14
- 230000000840 anti-viral effect Effects 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000006188 syrup Substances 0.000 description 11
- 235000020357 syrup Nutrition 0.000 description 11
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 241000700605 Viruses Species 0.000 description 7
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- QMPFMODFBNEYJH-UHFFFAOYSA-N methyl 1h-1,2,4-triazole-5-carboxylate Chemical compound COC(=O)C1=NC=NN1 QMPFMODFBNEYJH-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- -1 thiocarboxamido Chemical group 0.000 description 6
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000003443 antiviral agent Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 150000003833 nucleoside derivatives Chemical class 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 238000006884 silylation reaction Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- GUQHFZFTGHNVDG-UHFFFAOYSA-N 1h-1,2,4-triazole-5-carbonitrile Chemical compound N#CC1=NC=NN1 GUQHFZFTGHNVDG-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 238000007098 aminolysis reaction Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- MHSVUSZEHNVFKW-UHFFFAOYSA-N bis-4-nitrophenyl phosphate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1OP(=O)(O)OC1=CC=C([N+]([O-])=O)C=C1 MHSVUSZEHNVFKW-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- YBBDIXWREGHZRM-DYXQDRAXSA-N (3s,4r,5r)-2-chloro-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)oxolane Chemical compound C([C@H]1OC([C@H]([C@@H]1OCC=1C=CC=CC=1)OCC=1C=CC=CC=1)Cl)OCC1=CC=CC=C1 YBBDIXWREGHZRM-DYXQDRAXSA-N 0.000 description 2
- SJCDBQHCQSIZHN-UHFFFAOYSA-N 1,2-dihydrotriazole-3-carboxamide Chemical compound NC(=O)N1NNC=C1 SJCDBQHCQSIZHN-UHFFFAOYSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- 241000700647 Variola virus Species 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- ZRIUUUJAJJNDSS-UHFFFAOYSA-N ammonium phosphates Chemical compound [NH4+].[NH4+].[NH4+].[O-]P([O-])([O-])=O ZRIUUUJAJJNDSS-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 125000005521 carbonamide group Chemical group 0.000 description 2
- 125000005518 carboxamido group Chemical group 0.000 description 2
- 230000004656 cell transport Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000003147 glycosyl group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 2
- RFJYLFZDYHCYNF-UAKXSSHOSA-N methyl 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxylate Chemical compound N1=C(C(=O)OC)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RFJYLFZDYHCYNF-UAKXSSHOSA-N 0.000 description 2
- VQBGAUXDGQKKNT-UHFFFAOYSA-N methyl 1-trimethylsilyl-1,2,4-triazole-3-carboxylate Chemical compound COC(=O)C=1N=CN([Si](C)(C)C)N=1 VQBGAUXDGQKKNT-UHFFFAOYSA-N 0.000 description 2
- 208000009091 myxoma Diseases 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 208000009305 pseudorabies Diseases 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- ZEWJFUNFEABPGL-UHFFFAOYSA-N 1,2,4-triazole-3-carboxamide Chemical compound NC(=O)C=1N=CNN=1 ZEWJFUNFEABPGL-UHFFFAOYSA-N 0.000 description 1
- MXHRCPNRJAMMIM-ULQXZJNLSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidine-2,4-dione Chemical compound O=C1NC(=O)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 MXHRCPNRJAMMIM-ULQXZJNLSA-N 0.000 description 1
- FEOOHOXQNOVDKV-RKEPMNIXSA-N 1-[(3R,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)oxolan-2-yl]ethanone Chemical compound C(C)(=O)C1(O)[C@H](O)[C@H](O)[C@H](O1)CO FEOOHOXQNOVDKV-RKEPMNIXSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- VTHXSCUQGYRQPX-UHFFFAOYSA-N 1H-1,2,4-triazole-5-carboximidamide Chemical compound NC(=N)C=1N=CNN=1 VTHXSCUQGYRQPX-UHFFFAOYSA-N 0.000 description 1
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
- FFLUMYXAPXARJP-JBBNEOJLSA-N 3-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrole-2,5-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CC(=O)NC1=O FFLUMYXAPXARJP-JBBNEOJLSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- PZKFSRWSQOQYNR-UHFFFAOYSA-N 5-methyl-1h-1,2,4-triazole Chemical compound CC1=NC=NN1 PZKFSRWSQOQYNR-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006542 Bulbar palsy Diseases 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 description 1
- FFLUMYXAPXARJP-UHFFFAOYSA-N D-showdomycin Natural products OC1C(O)C(CO)OC1C1=CC(=O)NC1=O FFLUMYXAPXARJP-UHFFFAOYSA-N 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000010454 Experimental Liver Neoplasms Diseases 0.000 description 1
- 208000001688 Herpes Genitalis Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- XESARGFCSKSFID-UHFFFAOYSA-N Pyrazofurin Natural products OC1=C(C(=O)N)NN=C1C1C(O)C(O)C(CO)O1 XESARGFCSKSFID-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000287433 Turdus Species 0.000 description 1
- IXMTWJNGXZIMAL-FMKGYKFTSA-N [(2r,3r,4r,5r)-3,4-diacetyloxy-5-(3-cyano-1,2,4-triazol-1-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]1N1N=C(C#N)N=C1 IXMTWJNGXZIMAL-FMKGYKFTSA-N 0.000 description 1
- QSHDDOUJBYECFT-BJUDXGSMSA-N [200Hg] Chemical compound [200Hg] QSHDDOUJBYECFT-BJUDXGSMSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003622 anti-hsv Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000003865 brosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)S(*)(=O)=O 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- GAFINJXANQZOKT-UHFFFAOYSA-N cyano acetate Chemical compound CC(=O)OC#N GAFINJXANQZOKT-UHFFFAOYSA-N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000020176 deacylation Effects 0.000 description 1
- 238000005947 deacylation reaction Methods 0.000 description 1
- 238000007360 debenzoylation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 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
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 201000004946 genital herpes Diseases 0.000 description 1
- 201000010884 herpes simplex virus keratitis Diseases 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 208000037797 influenza A Diseases 0.000 description 1
- 208000037798 influenza B Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 1
- PUHIETBGRWTVIS-PMHJDTQVSA-N methyl 1-[(2r,3r,4r,5r)-3,4-dibenzoyloxy-5-(benzoyloxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxylate Chemical compound N1=C(C(=O)OC)N=CN1[C@H]1[C@H](OC(=O)C=2C=CC=CC=2)[C@H](OC(=O)C=2C=CC=CC=2)[C@@H](COC(=O)C=2C=CC=CC=2)O1 PUHIETBGRWTVIS-PMHJDTQVSA-N 0.000 description 1
- LLSQCRXJNSSQPO-UHFFFAOYSA-N methyl triazole-1-carboxylate Chemical compound COC(=O)N1C=CN=N1 LLSQCRXJNSSQPO-UHFFFAOYSA-N 0.000 description 1
- WPHGSKGZRAQSGP-UHFFFAOYSA-N methylenecyclohexane Natural products C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- XESARGFCSKSFID-FLLFQEBCSA-N pirazofurin Chemical compound OC1=C(C(=O)N)NN=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 XESARGFCSKSFID-FLLFQEBCSA-N 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940055764 triaz Drugs 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- C07H19/056—Triazole or tetrazole radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14901771A | 1971-06-01 | 1971-06-01 | |
| US24025272A | 1972-03-31 | 1972-03-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2220246A1 true DE2220246A1 (de) | 1972-12-14 |
Family
ID=26846393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19722220246 Withdrawn DE2220246A1 (de) | 1971-06-01 | 1972-04-25 | 1,2,4 Tnazol Nukleoside |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US3798209A (enExample) |
| JP (5) | JPS5527076B1 (enExample) |
| AR (1) | AR199463A1 (enExample) |
| AU (1) | AU461900B2 (enExample) |
| BE (1) | BE784195A (enExample) |
| BG (1) | BG22827A3 (enExample) |
| CA (1) | CA997756A (enExample) |
| CH (1) | CH614452A5 (enExample) |
| DD (1) | DD99791A5 (enExample) |
| DE (1) | DE2220246A1 (enExample) |
| DK (2) | DK143069C (enExample) |
| EG (1) | EG11406A (enExample) |
| ES (1) | ES403142A1 (enExample) |
| FR (1) | FR2140126B1 (enExample) |
| GB (1) | GB1353565A (enExample) |
| HK (1) | HK23876A (enExample) |
| HU (1) | HU167614B (enExample) |
| IE (1) | IE36478B1 (enExample) |
| IL (1) | IL39416A (enExample) |
| IN (1) | IN142290B (enExample) |
| IS (1) | IS913B6 (enExample) |
| LU (1) | LU65446A1 (enExample) |
| MC (1) | MC921A1 (enExample) |
| MY (1) | MY7600203A (enExample) |
| NL (1) | NL7207156A (enExample) |
| NO (1) | NO138805C (enExample) |
| RO (1) | RO62435A (enExample) |
| SE (3) | SE405604B (enExample) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2511829A1 (de) * | 1974-03-18 | 1975-09-25 | Icn Pharmaceuticals | N-substituierte 1,2,4-triazole |
| DE2511828A1 (de) * | 1974-03-18 | 1975-10-02 | Icn Pharmaceuticals | 1-(beta-d-ribofuranosyl)-1,2,4-triazolsaeureester |
| US10508117B2 (en) | 2014-09-16 | 2019-12-17 | Gilead Sciences, Inc. | Solid forms of a toll-like receptor modulator |
| US11110091B2 (en) | 2008-12-09 | 2021-09-07 | Gilead Sciences, Inc. | Modulators of toll-like receptors |
| US11116774B2 (en) | 2014-07-11 | 2021-09-14 | Gilead Sciences, Inc. | Modulators of toll-like receptors for the treatment of HIV |
| WO2021209563A1 (en) | 2020-04-16 | 2021-10-21 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
Families Citing this family (91)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3984396A (en) * | 1971-06-01 | 1976-10-05 | Icn Pharmaceuticals, Inc. | 1-(β,-D-ribofuranosyl)-1,2,4-triazole acid esters |
| DE2401449A1 (de) * | 1973-01-16 | 1974-07-25 | Voorhees | Pharmazeutische zusammensetzung zur linderung von hautproliferationserkrankungen |
| US3888843A (en) * | 1973-06-12 | 1975-06-10 | Toyo Jozo Kk | 4-carbamoyl-1-' -d-ribofuranosylimidazolium-5-olate |
| US3960836A (en) * | 1974-07-22 | 1976-06-01 | Eli Lilly And Company | Acylated derivatives of pyrazofurin and process for their preparation |
| US4007198A (en) * | 1975-05-01 | 1977-02-08 | American Cyanamid Company | Substituted 1,2,4-triazole carboxamide |
| US4138547A (en) * | 1977-12-22 | 1979-02-06 | Icn Pharmaceuticals, Inc. | Process for preparing 1,2,4-triazole nucleosides |
| JPS57146593A (en) * | 1981-03-09 | 1982-09-10 | Ajinomoto Co Inc | Preparation of ribofuranosyltriazole derivative |
| US4451648A (en) * | 1981-08-19 | 1984-05-29 | The United States Of America As Represented By The Department Of Health And Human Services | Process for the production of 2-β-D-ribofuranosylthiazole-4-carboxamide |
| US4531001A (en) * | 1982-03-23 | 1985-07-23 | Brigham Young University | 2-β-D-ribofuranosylselenazole-4-carboxamide compounds |
| US4446315A (en) * | 1982-09-24 | 1984-05-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adenosine 5'-triphosphate-4-carboxamide-ribofuranosylthiazole |
| JPS5964648U (ja) * | 1982-10-22 | 1984-04-28 | 阿波野 政晴 | 日覆用骨格 |
| BE902199A (fr) * | 1984-10-29 | 1985-07-31 | Vira Tek Inc | Procede de traitement medical de maladies virales utilisant le 1-beta-d-ribofurannosyl-1, 2,4-triazole-3-carboxamide. |
| NZ213370A (en) * | 1985-01-16 | 1989-03-29 | Vira Tek Inc | Method of treating viral infections of selected trees and field crops using ribavirin (1-b-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) or the 2,3,5-triacetyl or 5'-butyryl derivative thereof |
| DE3606634A1 (de) * | 1986-02-28 | 1987-09-03 | Mack Chem Pharm | Isohexid-nucleoside, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| ATE135914T1 (de) * | 1986-03-27 | 1996-04-15 | Gensia Inc | Aica riboside zur prophylaktischen behandlung von krankheiten mit einer verminderten durchblutung. |
| US4925930A (en) * | 1988-11-02 | 1990-05-15 | Nucleic Acid Research Institute | Synthesis and anti-leukemic activity of alkyl-1-(β-D-ribofuranosyl)[1,2,4]triazole-3-carboximidates |
| US5438131A (en) * | 1992-09-16 | 1995-08-01 | Bergstrom; Donald E. | 3-nitropyrrole nucleoside |
| YU47802A (sh) * | 1999-12-23 | 2006-03-03 | Ribapharm | Postupci i kompozicije za levovirin |
| US7638496B2 (en) * | 2000-02-15 | 2009-12-29 | Valeant Pharmaceuticals North America | Nucleoside analogs with carboxamidine modified monocyclic base |
| US6455508B1 (en) * | 2000-02-15 | 2002-09-24 | Kanda S. Ramasamy | Methods for treating diseases with tirazole and pyrrolo-pyrimidine ribofuranosyl nucleosides |
| US6495677B1 (en) | 2000-02-15 | 2002-12-17 | Kanda S. Ramasamy | Nucleoside compounds |
| MY164523A (en) * | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| PL359169A1 (en) * | 2000-05-26 | 2004-08-23 | Idenix (Cayman) Limited | Methods and compositions for treating flaviviruses and pestiviruses |
| US6815542B2 (en) * | 2000-06-16 | 2004-11-09 | Ribapharm, Inc. | Nucleoside compounds and uses thereof |
| AU2001220806A1 (en) * | 2000-08-22 | 2002-03-04 | Ribapharm Inc. | Improved specificity in treatment of diseases |
| WO2002044717A1 (en) * | 2000-12-01 | 2002-06-06 | Cornell Research Foundation | Animal model for flaviviridae infection |
| US20040014696A1 (en) * | 2000-12-07 | 2004-01-22 | Johnson Lau | Specificity in treatment of diseases |
| US6720000B2 (en) * | 2001-03-19 | 2004-04-13 | Three Rivers Pharmaceutical, Llc | Process for producing wet ribavirin pellets |
| DE60101056T2 (de) * | 2001-07-30 | 2004-05-19 | Clariant Life Science Molecules (Italia) S.P.A., Origgio | Verfahren zur Herstellung von Ribavirin |
| US7138376B2 (en) * | 2001-09-28 | 2006-11-21 | Idenix Pharmaceuticals, Inc. | Methods and compositions for treating hepatitis C virus using 4'-modified nucleosides |
| MXPA04004181A (es) * | 2001-11-02 | 2005-01-25 | Sandoz Ag | Procedimiento para preparar composiciones de ribavirina de alta carga, de rapida disolucion. |
| KR100411398B1 (ko) | 2001-12-06 | 2003-12-18 | 주식회사유한양행 | 베타-디-리보푸라노즈 유도체의 제조방법 |
| NZ537662A (en) * | 2002-06-28 | 2007-10-26 | Idenix Cayman Ltd | 2'-C-methyl-3'-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| CA2489552A1 (en) * | 2002-06-28 | 2004-01-08 | Idenix (Cayman) Limited | 2'-c-methyl-3'-o-l-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| US7608600B2 (en) * | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| TW200500374A (en) | 2002-06-28 | 2005-01-01 | Idenlx Cayman Ltd | 2' and 3' -nucleoside produrgs for treating flavivridae infections |
| US20040067877A1 (en) * | 2002-08-01 | 2004-04-08 | Schinazi Raymond F. | 2', 3'-Dideoxynucleoside analogues for the treatment or prevention of Flaviviridae infections |
| US7538094B2 (en) * | 2002-09-19 | 2009-05-26 | Three Rivers Pharmacueticals, Llc | Composition containing ribavirin and use thereof |
| SI1576138T1 (sl) | 2002-11-15 | 2017-07-31 | Idenix Pharmaceuticals Llc | 2'-metil nukleozidi v kombinaciji z interferon in flaviviridae mutacijo |
| ES2470771T3 (es) * | 2002-12-12 | 2014-06-24 | Idenix Pharmaceuticals, Inc | Procedimiento para la producción de nucle�sidos ramificados en 2' |
| EP1575971A4 (en) * | 2002-12-23 | 2008-03-05 | Idenix Cayman Ltd | PROCESS FOR THE PREPARATION OF 3-NUCLEOSIDE PRODRUGS |
| RU2005133093A (ru) * | 2003-03-28 | 2006-07-27 | Фармассет, Инк. (Us) | Соединения для лечения флавивирусных инфекций |
| PT1633766T (pt) | 2003-05-30 | 2019-06-04 | Gilead Pharmasset Llc | Análogos de nucleósido fluorado modificado |
| EP1658302B1 (en) * | 2003-07-25 | 2010-08-25 | IDENIX Pharmaceuticals, Inc. | Purine nucleoside analogues for treating diseases caused by flaviviridae including hepatitis c |
| WO2005018330A1 (en) * | 2003-08-18 | 2005-03-03 | Pharmasset, Inc. | Dosing regimen for flaviviridae therapy |
| US20050187192A1 (en) * | 2004-02-20 | 2005-08-25 | Kucera Pharmaceutical Company | Phospholipids for the treatment of infection by togaviruses, herpes viruses and coronaviruses |
| EP1912643A2 (en) * | 2004-06-23 | 2008-04-23 | Idenix (Cayman) Limited | 5-aza-7-deazapurine derivatives for treating infections with flaviviridae |
| CN101023094B (zh) * | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备 |
| SI3109244T1 (sl) * | 2004-09-14 | 2019-06-28 | Gilead Pharmasset Llc | Priprava 2'fluoro-2'-alkil-substituiranih ali drugih neobvezno substituiranih ribofuranozil pirimidinov in purinov in njihovih derivatov |
| EP2305696A3 (en) * | 2005-07-25 | 2011-10-12 | Intermune, Inc. | Macrocyclic inhibitors of Hepatitis C virus replication |
| JP2009511595A (ja) * | 2005-10-11 | 2009-03-19 | インターミューン・インコーポレーテッド | Ｃ型肝炎ウイルスの複製を阻害する化合物および方法 |
| WO2007075876A2 (en) * | 2005-12-23 | 2007-07-05 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| MX2008013119A (es) | 2006-04-11 | 2008-10-21 | Novartis Ag | Inhibidores de hcv/vih y sus usos. |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| EP2201953A4 (en) | 2007-08-27 | 2011-08-03 | Univ Nagoya Nat Univ Corp | USE OF RIBAVIRIN IN BLOOD CLEANING DISORDERS |
| JPWO2009028575A1 (ja) | 2007-08-27 | 2010-12-02 | 国立大学法人名古屋大学 | 血液凝固第ｖｉｉ因子プロモーターの活性化剤及びその利用 |
| US20090082414A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched viramidine |
| WO2009105258A1 (en) | 2008-02-22 | 2009-08-27 | Nektar Therapeutics Al, Corporation | Oligomer conjugates of heteropentacyclic nucleosides |
| TW200946541A (en) * | 2008-03-27 | 2009-11-16 | Idenix Pharmaceuticals Inc | Solid forms of an anti-HIV phosphoindole compound |
| EP2282762A2 (en) * | 2008-04-15 | 2011-02-16 | Intermune, Inc. | Novel macrocyclic inhibitors of hepatitis c virus replication |
| US8173621B2 (en) * | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| CA2740728A1 (en) * | 2008-10-15 | 2010-04-22 | Intermune, Inc. | Therapeutic antiviral peptides |
| CN102753563A (zh) * | 2008-12-23 | 2012-10-24 | 吉利德制药有限责任公司 | 核苷类似物 |
| SG172363A1 (en) | 2008-12-23 | 2011-07-28 | Pharmasset Inc | Synthesis of purine nucleosides |
| AR074897A1 (es) | 2008-12-23 | 2011-02-23 | Pharmasset Inc | Fosforamidatos de nucleosidos |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| TWI576352B (zh) | 2009-05-20 | 2017-04-01 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| WO2011038293A1 (en) * | 2009-09-28 | 2011-03-31 | Intermune, Inc. | Cyclic peptide inhibitors of hepatitis c virus replication |
| WO2011041551A1 (en) * | 2009-10-01 | 2011-04-07 | Intermune, Inc. | Therapeutic antiviral peptides |
| WO2011076923A1 (en) | 2009-12-23 | 2011-06-30 | Institut National De La Sante Et De La Recherche Medicale | Inhibitor for inosine monophosphate (imp) dehydrogenase and/or viral rna polymerase for treatment of hepatitis e |
| US8933110B2 (en) | 2010-01-25 | 2015-01-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| EP2528436A4 (en) * | 2010-01-25 | 2013-07-10 | Enanta Pharm Inc | INHIBITORS OF HEPATITIS C VIRUS |
| PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu |
| WO2011123668A2 (en) | 2010-03-31 | 2011-10-06 | Pharmasset, Inc. | Stereoselective synthesis of phosphorus containing actives |
| JP5909495B2 (ja) | 2010-10-08 | 2016-04-26 | ノバルティス アーゲー | スルファミドｎｓ３阻害剤のビタミンｅ製剤 |
| EP2646453A1 (en) | 2010-11-30 | 2013-10-09 | Gilead Pharmasset LLC | Compounds |
| CA2822037A1 (en) | 2010-12-20 | 2012-06-28 | Gilead Sciences, Inc. | Methods for treating hcv |
| CA2752008A1 (en) | 2011-09-13 | 2013-03-13 | Universite De Montreal | Combination therapy using ribavirin as elf4e inhibitor |
| SG10201602044WA (en) | 2011-09-16 | 2016-04-28 | Gilead Pharmassett Llc | Methods For Treating HCV |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| CA2889903C (en) | 2012-10-29 | 2021-03-09 | Manjinder Singh Phull | Antiviral phosphonate analogues and process for preparation thereof |
| US20140205566A1 (en) | 2012-11-30 | 2014-07-24 | Novartis Ag | Cyclic nucleuoside derivatives and uses thereof |
| AU2014202687A1 (en) | 2013-01-31 | 2014-08-14 | Gilead Pharmasset Llc | Combination formulation of two antiviral compounds |
| SI3038601T1 (sl) | 2013-08-27 | 2020-07-31 | Gilead Pharmasset Llc | Formulacija kombinacije dveh protivirusnih spojin |
| EP2959888A1 (en) | 2014-06-23 | 2015-12-30 | Sanovel Ilac Sanayi ve Ticaret A.S. | A novel pharmaceutical composition of sofosbuvir and ribavirin |
| EP2959891A1 (en) | 2014-06-23 | 2015-12-30 | Sanovel Ilac Sanayi ve Ticaret A.S. | Modified release pharmaceutical compositions of sofosbuvir and ribavirin |
| EA201692507A1 (ru) | 2014-06-23 | 2017-04-28 | Сановель Илач Санайи Ве Тиджарет А.Ш. | Фармацевтические комбинации софосбувира и рибавирина |
| UY37381A (es) | 2016-08-30 | 2018-03-23 | Glaxosmithkline Ip No 2 Ltd | Compuestos que inhiben proteasas 3c y 3cl y métodos de uso de los mismos |
| CN110713464B (zh) * | 2019-10-31 | 2023-03-31 | 重庆大学 | 一种芳基1,2,4-三氮唑核苷化合物及其制备方法和应用 |
-
1972
- 1972-03-31 US US00240252A patent/US3798209A/en not_active Expired - Lifetime
- 1972-04-25 DE DE19722220246 patent/DE2220246A1/de not_active Withdrawn
- 1972-05-11 AU AU42157/72A patent/AU461900B2/en not_active Expired
- 1972-05-11 IL IL39416A patent/IL39416A/xx unknown
- 1972-05-12 DK DK237072A patent/DK143069C/da not_active IP Right Cessation
- 1972-05-12 IE IE638/72A patent/IE36478B1/en unknown
- 1972-05-13 GB GB2241972A patent/GB1353565A/en not_active Expired
- 1972-05-13 JP JP4760172A patent/JPS5527076B1/ja active Pending
- 1972-05-15 IS IS2075A patent/IS913B6/is unknown
- 1972-05-20 EG EG203/72A patent/EG11406A/xx active
- 1972-05-24 ES ES403142A patent/ES403142A1/es not_active Expired
- 1972-05-25 CH CH776572A patent/CH614452A5/xx not_active IP Right Cessation
- 1972-05-26 NL NL7207156A patent/NL7207156A/xx not_active Application Discontinuation
- 1972-05-26 NO NO1858/72A patent/NO138805C/no unknown
- 1972-05-29 DD DD163262A patent/DD99791A5/xx unknown
- 1972-05-30 AR AR242262A patent/AR199463A1/es active
- 1972-05-31 BE BE784195A patent/BE784195A/xx unknown
- 1972-05-31 FR FR7219501A patent/FR2140126B1/fr not_active Expired
- 1972-05-31 MC MC995A patent/MC921A1/fr unknown
- 1972-05-31 SE SE7207131A patent/SE405604B/xx unknown
- 1972-05-31 HU HUIE507A patent/HU167614B/hu unknown
- 1972-05-31 CA CA143,816A patent/CA997756A/en not_active Expired
- 1972-05-31 BG BG020615A patent/BG22827A3/xx unknown
- 1972-06-01 LU LU65446D patent/LU65446A1/xx unknown
- 1972-06-01 RO RO7200071105A patent/RO62435A/ro unknown
-
1974
- 1974-05-09 IN IN1026/CAL/1974A patent/IN142290B/en unknown
-
1976
- 1976-04-22 HK HK238/76*UA patent/HK23876A/xx unknown
- 1976-11-12 DK DK509876A patent/DK509876A/da unknown
- 1976-12-30 MY MY203/76A patent/MY7600203A/xx unknown
-
1978
- 1978-01-13 JP JP325978A patent/JPS5387356A/ja active Granted
- 1978-01-13 JP JP325878A patent/JPS5395974A/ja active Granted
- 1978-01-13 JP JP326078A patent/JPS53124271A/ja active Pending
- 1978-01-13 JP JP326178A patent/JPS53108973A/ja active Pending
- 1978-02-20 SE SE7801926A patent/SE7801926L/xx unknown
- 1978-02-20 SE SE7801925A patent/SE7801925L/xx unknown
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2511829A1 (de) * | 1974-03-18 | 1975-09-25 | Icn Pharmaceuticals | N-substituierte 1,2,4-triazole |
| DE2511828A1 (de) * | 1974-03-18 | 1975-10-02 | Icn Pharmaceuticals | 1-(beta-d-ribofuranosyl)-1,2,4-triazolsaeureester |
| DE2560551C2 (enExample) * | 1974-03-18 | 1989-02-23 | Viratek, Inc., Covina, Calif., Us | |
| US11110091B2 (en) | 2008-12-09 | 2021-09-07 | Gilead Sciences, Inc. | Modulators of toll-like receptors |
| US11116774B2 (en) | 2014-07-11 | 2021-09-14 | Gilead Sciences, Inc. | Modulators of toll-like receptors for the treatment of HIV |
| US10508117B2 (en) | 2014-09-16 | 2019-12-17 | Gilead Sciences, Inc. | Solid forms of a toll-like receptor modulator |
| US11072615B2 (en) | 2014-09-16 | 2021-07-27 | Gilead Sciences, Inc. | Solid forms of a toll-like receptor modulator |
| US11773098B2 (en) | 2014-09-16 | 2023-10-03 | Gilead Sciences, Inc. | Solid forms of a toll-like receptor modulator |
| US12486271B2 (en) | 2014-09-16 | 2025-12-02 | Gilead Sciences, Inc. | Solid forms of a toll-like receptor modulator |
| WO2021209563A1 (en) | 2020-04-16 | 2021-10-21 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2220246A1 (de) | 1,2,4 Tnazol Nukleoside | |
| EP0316704B1 (de) | Fluorcytidinderivate, deren Herstellung und Arzneimittel, die diese Derivate enthalten | |
| AT390000B (de) | Verwendung von 3'-azido-3'-desoxythymidin oder eines pharmazeutisch annehmbaren derivats hievon zur herstellung von medikamenten | |
| DE60005501T2 (de) | 4'-c-ethynyl-pyrimidine nukleoside | |
| DE2756653C2 (de) | 5'-Deoxy-5-fluorcytidin und 5'- Deoxy-5-fluoruridin, deren Isopropylidenderivate und Salze und Verfahren zu deren Herstellung | |
| DE3739366A1 (de) | Desaza-purin-nucleosid-derivate, verfahren zu deren herstellung sowie deren verwendung bei der nucleinsaeure-sequenzierung sowie als antivirale mittel | |
| EP0484333A1 (de) | Nucleosid-derivate und deren verwendung als arzneimittel. | |
| DE19823484A1 (de) | 5'-Desoxycytidin-derivate | |
| CH634310A5 (de) | Verfahren zur herstellung neuer pyrimidonderivate. | |
| DE3390162T1 (de) | Desoxyuridinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Pharmazeutika | |
| DE2546073A1 (de) | Nucleotid-derivate und verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln | |
| DE2331223C2 (de) | S-substituierte-2-Thioadenosine, deren 5'-Monophosphate, Verfahren zu deren Herstellung und Arzneimittel, welche diese enthalten | |
| DE2552293A1 (de) | Antileukaemische verbindungen, verfahren zu ihrer herstellung und sie enthaltende arzneimittel | |
| DE69431304T2 (de) | Nukleoside und nukleotide mit vergrösserten ringen | |
| EP0763047B1 (de) | Neues verfahren zur herstellung von nucleosiden | |
| DE2735378C2 (enExample) | ||
| DE2365719A1 (de) | Arabinofuranosyl-6-azacytosine und verfahren zu ihrer herstellung | |
| CH467277A (de) | Verfahren zur Herstellung von Cobalticorrinoiden | |
| DE68928127T2 (de) | 2'-Methylidenpyrimidinnukleosidverbindungen, ihre Verwendung und Verfahren zu ihrer Herstellung | |
| DE2511828C2 (enExample) | ||
| DE69007775T2 (de) | 5'-alkylphosphonylnukleoside als antivirale verbindungen. | |
| DE69533856T2 (de) | L-pyranosyl-nukleoside | |
| DE2156637A1 (de) | Purinzuckerderivate, Verfahren zu ihrer Herstellung und ihrer Verwendung | |
| DE2324130A1 (de) | Neue 2-substituierte adenosin-3',5'cyclomonophosphate | |
| DE2626792A1 (de) | Acylderivate von adenosin-5'-monophosphorsaeure, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzung |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |