CS277006B6 - Process for preparing antiviral substances - Google Patents

Process for preparing antiviral substances Download PDF

Info

Publication number: CS277006B6
Authority: CS; Czechoslovakia
Prior art keywords: purine; arabinofuranosyl; methoxy; compound; formula
Prior art date: 1987-05-30

Application number

CS883635A

Other languages

Czech (cs)

English (en)

Other versions

CS8803635A2 (en

Inventor

Thomas Anthony Krenitsky

Georg Walter Koszalka

Lynda Addington Jones

Devron Randolph Averett

Allan Ray Moorman

Original Assignee

Wellcome Found

Priority date (The priority date 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 date listed.)

1987-05-30

Filing date

1988-05-27

Publication date

1992-11-18

1988-05-27 Application filed by Wellcome Found filed Critical Wellcome Found

1990-09-12 Publication of CS8803635A2 publication Critical patent/CS8803635A2/cs

1992-11-18 Publication of CS277006B6 publication Critical patent/CS277006B6/cs

Links

238000004519 manufacturing process Methods 0.000 title claims description 11
239000000126 substance Substances 0.000 title description 17
230000000840 anti-viral effect Effects 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 75
-1 purine arabinosides Chemical class 0.000 claims abstract description 47
238000000034 method Methods 0.000 claims abstract description 27
150000002148 esters Chemical class 0.000 claims abstract description 26
241000701085 Human alphaherpesvirus 3 Species 0.000 claims abstract description 22
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims abstract description 12
238000011282 treatment Methods 0.000 claims abstract description 12
238000002360 preparation method Methods 0.000 claims abstract description 9
238000011321 prophylaxis Methods 0.000 claims abstract description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 77
229910052757 nitrogen Inorganic materials 0.000 claims description 72
239000004480 active ingredient Substances 0.000 claims description 55
239000000463 material Substances 0.000 claims description 27
238000006243 chemical reaction Methods 0.000 claims description 26
208000015181 infectious disease Diseases 0.000 claims description 14
241000701022 Cytomegalovirus Species 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
229910052801 chlorine Inorganic materials 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
125000003277 amino group Chemical group 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
208000036142 Viral infection Diseases 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
239000001257 hydrogen Substances 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
230000009385 viral infection Effects 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
150000005840 aryl radicals Chemical class 0.000 claims description 3
150000001733 carboxylic acid esters Chemical class 0.000 claims description 3
150000005690 diesters Chemical class 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
150000003254 radicals Chemical class 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
150000005691 triesters Chemical class 0.000 claims description 3
WVGPGNPCZPYCLK-QRKAXHLRSA-N (2r,3s,4s,5r)-2-[6-(dimethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N(C)C)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O WVGPGNPCZPYCLK-QRKAXHLRSA-N 0.000 claims description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
IRZDOONJRAFUQI-LJGDNWOOSA-N [(2r,3s,4s,5r)-3,4-dihydroxy-5-(6-methoxypurin-9-yl)oxolan-2-yl]methyl 4-methylbenzoate Chemical compound C([C@H]1O[C@H]([C@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)OC)OC(=O)C1=CC=C(C)C=C1 IRZDOONJRAFUQI-LJGDNWOOSA-N 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
229940083251 peripheral vasodilators purine derivative Drugs 0.000 claims description 2
150000003212 purines Chemical group 0.000 claims description 2
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
VPBXAOGLYOZWSD-UHFFFAOYSA-N CCNC1(C(CCCN1N(C)C)OC)NC Chemical compound CCNC1(C(CCCN1N(C)C)OC)NC VPBXAOGLYOZWSD-UHFFFAOYSA-N 0.000 claims 1
XBNIJOKVGOETFF-MBMVNNNZSA-N [(2r,3s,4s,5r)-3,4-dihydroxy-5-(6-methoxypurin-9-yl)oxolan-2-yl]methyl 4-aminobenzoate Chemical compound C([C@H]1O[C@H]([C@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)OC)OC(=O)C1=CC=C(N)C=C1 XBNIJOKVGOETFF-MBMVNNNZSA-N 0.000 claims 1
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000000714 pyrimidinyl group Chemical group 0.000 claims 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims 1
206010011831 Cytomegalovirus infection Diseases 0.000 abstract description 3
208000005181 Varicella Zoster Virus Infection Diseases 0.000 abstract 1
208000010531 varicella zoster infection Diseases 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 222
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 132
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 124
239000000047 product Substances 0.000 description 105
239000000203 mixture Substances 0.000 description 102
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 92
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
229910052799 carbon Inorganic materials 0.000 description 69
239000000243 solution Substances 0.000 description 58
239000000741 silica gel Substances 0.000 description 57
229910002027 silica gel Inorganic materials 0.000 description 57
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 46
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 45
238000005481 NMR spectroscopy Methods 0.000 description 42
238000004949 mass spectrometry Methods 0.000 description 42
238000003818 flash chromatography Methods 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 36
239000002904 solvent Substances 0.000 description 36
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
238000007792 addition Methods 0.000 description 23
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
239000003826 tablet Substances 0.000 description 22
UQQHOWKTDKKTHO-ICQCTTRCSA-N (2r,3s,4s,5r)-2-(hydroxymethyl)-5-(6-methoxypurin-9-yl)oxolane-3,4-diol Chemical compound C1=NC=2C(OC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O UQQHOWKTDKKTHO-ICQCTTRCSA-N 0.000 description 21
239000011347 resin Substances 0.000 description 20
229920005989 resin Polymers 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
239000003921 oil Substances 0.000 description 18
235000019198 oils Nutrition 0.000 description 18
239000002775 capsule Substances 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000000706 filtrate Substances 0.000 description 16
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
239000000377 silicon dioxide Substances 0.000 description 16
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
229910052786 argon Inorganic materials 0.000 description 15
210000004027 cell Anatomy 0.000 description 15
239000000725 suspension Substances 0.000 description 15
239000007787 solid Substances 0.000 description 14
239000004615 ingredient Substances 0.000 description 13
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
101710101148 Probable 6-oxopurine nucleoside phosphorylase Proteins 0.000 description 11
102000030764 Purine-nucleoside phosphorylase Human genes 0.000 description 11
239000012043 crude product Substances 0.000 description 11
102000006405 Uridine phosphorylase Human genes 0.000 description 10
108010019092 Uridine phosphorylase Proteins 0.000 description 10
241000700605 Viruses Species 0.000 description 10
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
DRTQHJPVMGBUCF-CCXZUQQUSA-N arauridine Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-CCXZUQQUSA-N 0.000 description 9
201000010099 disease Diseases 0.000 description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
239000000843 powder Substances 0.000 description 9
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 8
239000006260 foam Substances 0.000 description 8
239000008101 lactose Substances 0.000 description 8
235000019359 magnesium stearate Nutrition 0.000 description 8
TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 8
229910000160 potassium phosphate Inorganic materials 0.000 description 8
235000011009 potassium phosphates Nutrition 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
150000003839 salts Chemical class 0.000 description 8
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
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ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 5
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 5
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
235000012538 ammonium bicarbonate Nutrition 0.000 description 5
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238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
238000002844 melting Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
238000000746 purification Methods 0.000 description 5
238000003756 stirring Methods 0.000 description 5
238000004809 thin layer chromatography Methods 0.000 description 5
239000001226 triphosphate Substances 0.000 description 5
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 4
102000002260 Alkaline Phosphatase Human genes 0.000 description 4
108020004774 Alkaline Phosphatase Proteins 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
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238000013270 controlled release Methods 0.000 description 4
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WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
238000011049 filling Methods 0.000 description 4
238000009472 formulation Methods 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
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238000012746 preparative thin layer chromatography Methods 0.000 description 4
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KWIPUXXIFQQMKN-UHFFFAOYSA-N 2-azaniumyl-3-(4-cyanophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=C(C#N)C=C1 KWIPUXXIFQQMKN-UHFFFAOYSA-N 0.000 description 2
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MRWXACSTFXYYMV-FDDDBJFASA-N nebularine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC=C2N=C1 MRWXACSTFXYYMV-FDDDBJFASA-N 0.000 description 1
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238000007911 parenteral administration Methods 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
238000003359 percent control normalization Methods 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008251 pharmaceutical emulsion Substances 0.000 description 1
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125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
WRMXOVHLRUVREB-UHFFFAOYSA-N phosphono phosphate;tributylazanium Chemical compound OP(O)(=O)OP([O-])([O-])=O.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC WRMXOVHLRUVREB-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000004800 polyvinyl chloride Substances 0.000 description 1
229920000915 polyvinyl chloride Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
238000003825 pressing Methods 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
108010043671 prostatic acid phosphatase Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000306 recurrent effect Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
239000000523 sample Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 1
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235000019698 starch Nutrition 0.000 description 1
229940071117 starch glycolate Drugs 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
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230000002459 sustained effect Effects 0.000 description 1
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235000020357 syrup Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229960004906 thiomersal Drugs 0.000 description 1
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238000002054 transplantation Methods 0.000 description 1
DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
235000011178 triphosphate Nutrition 0.000 description 1
125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
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239000007762 w/o emulsion Substances 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
- C07H19/16—Purine radicals
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Communicable Diseases (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Oncology (AREA)
Pharmacology & Pharmacy (AREA)
Virology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Plant Substances (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)

CS883635A 1987-05-30 1988-05-27 Process for preparing antiviral substances CS277006B6 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB878712745A GB8712745D0 (en)	1987-05-30	1987-05-30	Antiviral compounds

Publications (2)

Publication Number	Publication Date
CS8803635A2 CS8803635A2 (en)	1990-09-12
CS277006B6 true CS277006B6 (en)	1992-11-18

Family

ID=10618179

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS883635A CS277006B6 (en)	1987-05-30	1988-05-27	Process for preparing antiviral substances

Country Status (31)

Country	Link
US (2)	US5424295A (ar)
EP (1)	EP0294114B1 (ar)
JP (1)	JP2667873B2 (ar)
KR (1)	KR970009474B1 (ar)
CN (1)	CN1020107C (ar)
AT (1)	ATE142636T1 (ar)
AU (1)	AU622403B2 (ar)
CA (1)	CA1330990C (ar)
CS (1)	CS277006B6 (ar)
CY (2)	CY2001A (ar)
DD (2)	DD293962A5 (ar)
DE (2)	DE122008000003I2 (ar)
DK (1)	DK171670B1 (ar)
ES (1)	ES2091750T3 (ar)
FI (1)	FI89805C (ar)
GB (1)	GB8712745D0 (ar)
GR (1)	GR3021257T3 (ar)
HK (1)	HK78497A (ar)
HU (2)	HU199870B (ar)
IL (1)	IL86531A (ar)
LU (1)	LU91370I2 (ar)
MC (1)	MC1935A1 (ar)
MY (1)	MY103567A (ar)
NL (1)	NL300302I2 (ar)
NO (2)	NO172543C (ar)
NZ (1)	NZ224813A (ar)
PH (1)	PH27292A (ar)
PL (1)	PL157684B1 (ar)
PT (1)	PT87592B (ar)
SA (1)	SA99200688A (ar)
ZA (2)	ZA883829B (ar)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8712745D0 (en) *	1987-05-30	1987-07-01	Wellcome Found	Antiviral compounds
US6054441A (en) *	1987-10-28	2000-04-25	Pro-Neuron, Inc.	Oxypurine nucleosides and their congeners, and acyl derivatives thereof, for improvement of hematopoiesis
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1987
- 1987-05-30 GB GB878712745A patent/GB8712745D0/en active Pending
1988
- 1988-05-27 FI FI882511A patent/FI89805C/fi not_active IP Right Cessation
- 1988-05-27 AU AU16718/88A patent/AU622403B2/en not_active Expired
- 1988-05-27 NZ NZ224813A patent/NZ224813A/en unknown
- 1988-05-27 MC MC881981A patent/MC1935A1/xx unknown
- 1988-05-27 MY MYPI88000569A patent/MY103567A/en unknown
- 1988-05-27 DE DE122008000003C patent/DE122008000003I2/de active Active
- 1988-05-27 KR KR1019880006295A patent/KR970009474B1/ko not_active IP Right Cessation
- 1988-05-27 CA CA000567966A patent/CA1330990C/en not_active Expired - Lifetime
- 1988-05-27 EP EP88304813A patent/EP0294114B1/en not_active Expired - Lifetime
- 1988-05-27 PT PT87592A patent/PT87592B/pt not_active IP Right Cessation
- 1988-05-27 AT AT88304813T patent/ATE142636T1/de active
- 1988-05-27 HU HU882706A patent/HU199870B/hu active Protection Beyond IP Right Term
- 1988-05-27 NO NO882357A patent/NO172543C/no not_active IP Right Cessation
- 1988-05-27 DD DD88340139A patent/DD293962A5/de not_active IP Right Cessation
- 1988-05-27 ZA ZA883829A patent/ZA883829B/xx unknown
- 1988-05-27 PL PL1988272729A patent/PL157684B1/pl unknown
- 1988-05-27 DD DD88316143A patent/DD282694A5/de not_active IP Right Cessation
- 1988-05-27 DE DE3855522T patent/DE3855522T2/de not_active Expired - Lifetime
- 1988-05-27 HU HU895829A patent/HU205001B/hu unknown
- 1988-05-27 CN CN88103820A patent/CN1020107C/zh not_active Expired - Lifetime
- 1988-05-27 ES ES88304813T patent/ES2091750T3/es not_active Expired - Lifetime
- 1988-05-27 JP JP63128562A patent/JP2667873B2/ja not_active Expired - Lifetime
- 1988-05-27 DK DK289788A patent/DK171670B1/da not_active IP Right Cessation
- 1988-05-27 CS CS883635A patent/CS277006B6/cs not_active IP Right Cessation
- 1988-05-27 IL IL86531A patent/IL86531A/xx active Protection Beyond IP Right Term
1989
- 1989-09-01 PH PH39191A patent/PH27292A/en unknown
- 1989-10-05 ZA ZA897598A patent/ZA897598B/xx unknown
1993
- 1993-08-23 US US08/110,487 patent/US5424295A/en not_active Expired - Lifetime
1995
- 1995-03-14 US US08/403,363 patent/US5539098A/en not_active Expired - Lifetime
1996
- 1996-10-03 GR GR960402608T patent/GR3021257T3/el unknown
1997
- 1997-06-12 HK HK78497A patent/HK78497A/xx not_active IP Right Cessation
- 1997-12-05 CY CY200197A patent/CY2001A/xx unknown
1999
- 1999-10-18 SA SA99200688A patent/SA99200688A/ar unknown
2007
- 2007-10-10 LU LU91370C patent/LU91370I2/fr unknown
- 2007-11-02 NL NL300302C patent/NL300302I2/nl unknown
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Also Published As

Publication number	Publication date
ATE142636T1 (de)	1996-09-15
NO882357D0 (no)	1988-05-27
JP2667873B2 (ja)	1997-10-27
IL86531A0 (en)	1988-11-15
PL272729A1 (en)	1989-02-06
NO172543B (no)	1993-04-26
DE122008000003I1 (de)	2008-04-17
EP0294114A3 (en)	1990-01-24
FI882511A0 (fi)	1988-05-27
CY2008001I1 (el)	2009-11-04
US5424295A (en)	1995-06-13
GB8712745D0 (en)	1987-07-01
ZA883829B (en)	1990-01-31
ES2091750T3 (es)	1996-11-16
AU622403B2 (en)	1992-04-09
NO172543C (no)	1993-08-04
EP0294114A2 (en)	1988-12-07
DE3855522T2 (de)	1997-02-06
CA1330990C (en)	1994-07-26
DE122008000003I2 (de)	2010-02-04
CY2008001I2 (el)	2009-11-04
SA99200688A (ar)	2005-12-03
DD282694A5 (de)	1990-09-19
NO2007016I2 (no)	2008-06-23
PL157684B1 (pl)	1992-06-30
CS8803635A2 (en)	1990-09-12
NL300302I1 (nl)	2008-01-02
IL86531A (en)	1993-07-08
GR3021257T3 (en)	1997-01-31
MC1935A1 (fr)	1989-05-19
NL300302I2 (nl)	2008-05-01
FI89805B (fi)	1993-08-13
EP0294114B1 (en)	1996-09-11
FI882511A (fi)	1988-12-01
US5539098A (en)	1996-07-23
JPS63310831A (ja)	1988-12-19
HU205001B (en)	1992-03-30
NZ224813A (en)	1991-04-26
HK78497A (en)	1997-06-20
DD293962A5 (de)	1991-09-19
ZA897598B (en)	1990-01-31
DK289788A (da)	1988-12-01
PH27292A (en)	1993-05-04
HU895829D0 (en)	1990-01-28
HU199870B (en)	1990-03-28
DK289788D0 (da)	1988-05-27
PT87592A (pt)	1989-05-31
CY2001A (en)	1997-12-05
LU91370I2 (fr)	2007-12-10
KR970009474B1 (ko)	1997-06-13
AU1671888A (en)	1988-12-01
FI89805C (fi)	1993-11-25
NO2007016I1 (no)	2008-01-14
DE3855522D1 (de)	1996-10-17
HUT47129A (en)	1989-01-30
PT87592B (pt)	1992-09-30
KR880013967A (ko)	1988-12-22
CN1020107C (zh)	1993-03-17
CN1031233A (zh)	1989-02-22
NO882357L (no)	1988-12-01
DK171670B1 (da)	1997-03-10
MY103567A (en)	1993-08-28

Legal Events

Date	Code	Title	Description
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2009-01-21	MK4A	Patent expired	Effective date: 20080527

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CS277006B6 (en)	1992-11-18	Process for preparing antiviral substances
CN101321775B (zh)	2012-05-23	用于治疗疟疾的odcase抑制剂
Verheggen et al.	1993	Synthesis and antiherpes virus activity of 1, 5-anhydrohexitol nucleosides
EP0484333B1 (de)	1995-11-15	Nucleosid-derivate und deren verwendung als arzneimittel
US6211158B1 (en)	2001-04-03	Desazapurine-nucleotide derivatives, processes for the preparation thereof, pharmaceutical compositions containing them and the use thereof for nucleic acid sequencing and as antiviral agents
US20030008841A1 (en)	2003-01-09	Anti-HCV nucleoside derivatives
JPH07116042B2 (ja)	1995-12-13	ヌクレオシド化合物
HU227679B1 (en)	2011-11-28	Benzimidazole derivatives with antiviral activity, pharmaceutical compns. contg. them, process for preparing them and intermediates thereof
JP2004532184A (ja)	2004-10-21	Ｒｎａ依存性ｒｎａウィルスポリメラーゼ阻害薬としてのヌクレオシド誘導体
HU199867B (en)	1990-03-28	Process for production of 5-substituated pirimidin nucleosides
PT95261A (pt)	1991-05-22	Processo para a preparacao de derivados de 2'-desoxi-2'-fluoro-ribonucleosidos e de composicoes farmaceuticas que os contem
NO328229B1 (no)	2010-01-11	Fremgangsmate for fremstilling av di (uridin 5') - tetrafosfat) og salter derav, deres anvendelse og sammensetninger inneholdende de samme
JPH0291022A (ja)	1990-03-30	Ａｚｔまたはリバビリンと組み合わせたジデオキシ炭素環式ヌクレオシド
US5459256A (en)	1995-10-17	Lipophilic, aminohydrolase-activated prodrugs
JPS63258891A (ja)	1988-10-26	治療用ヌクレオシド化合物
CZ212698A3 (cs)	1998-12-16	Benzimidazolové deriváty a farmaceutický prostředek
US5420115A (en)	1995-05-30	Method for the treatment of protoza infections with 21 -deoxy-21 -fluoropurine nucleosides
EP0620734A1 (en)	1994-10-26	Therapeutic nucleosides
US20030119762A1 (en)	2003-06-26	5'-substituted-ribofuranosyl benzimidazoles as antiviral agents
RU2112765C1 (ru)	1998-06-10	ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ПРОЯВЛЯЮЩАЯ АКТИВНОСТЬ ПРОТИВ ВИРУСНОЙ ИНФЕКЦИИ И β D-АРАБИНОФУРАНОЗИЛ-2-АМИНО-6-МЕТОКСИ-9Н-ПУРИНЫ
RU2039752C1 (ru)	1995-07-20	Способ получения замещенных пуриновых арабинозидов или его фармацевтически приемлемых производных