JP2001515900A - 抗ウイルス薬 - Google Patents
抗ウイルス薬Info
- Publication number
- JP2001515900A JP2001515900A JP2000510734A JP2000510734A JP2001515900A JP 2001515900 A JP2001515900 A JP 2001515900A JP 2000510734 A JP2000510734 A JP 2000510734A JP 2000510734 A JP2000510734 A JP 2000510734A JP 2001515900 A JP2001515900 A JP 2001515900A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- amino
- hydrogen
- hydrazino
- alkoxy
- 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- Withdrawn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
- 239000003443 antiviral agent Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- -1 hydrazino, hydroxylamino, benzyloxy Chemical group 0.000 claims abstract description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 21
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 16
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 16
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical class 0.000 claims abstract description 16
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 208000002672 hepatitis B Diseases 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 12
- 238000001727 in vivo Methods 0.000 claims description 12
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- 208000036142 Viral infection Diseases 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 230000009385 viral infection Effects 0.000 claims description 7
- ANFNNSIOGODJDN-UHFFFAOYSA-N 2-amino-9-[3-hydroxy-2-(hydroxymethyl)propyl]-3h-purin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N(CC(CO)CO)C=N2 ANFNNSIOGODJDN-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- ULDVPVQNHPIANB-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]propane-1,3-diol Chemical compound NC1=NC=NC2=C1N=CN2CC(CO)CO ULDVPVQNHPIANB-UHFFFAOYSA-N 0.000 claims description 2
- KNFZVBOYMBHOOV-UHFFFAOYSA-N 2-amino-9-[(2-propan-2-yl-1,3-dioxan-5-yl)methyl]-3h-purin-6-one Chemical compound C1OC(C(C)C)OCC1CN1C(NC(N)=NC2=O)=C2N=C1 KNFZVBOYMBHOOV-UHFFFAOYSA-N 0.000 claims description 2
- PZWHCMYKGSVWRE-UHFFFAOYSA-N 9-[(2-propan-2-yl-1,3-dioxan-5-yl)methyl]purin-6-amine Chemical compound C1OC(C(C)C)OCC1CN1C2=NC=NC(N)=C2N=C1 PZWHCMYKGSVWRE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000011282 treatment Methods 0.000 abstract description 11
- 230000002265 prevention Effects 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 35
- 239000007787 solid Substances 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 14
- 239000000377 silicon dioxide Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 150000005690 diesters Chemical class 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- IBAOFQIOOBQLHE-UHFFFAOYSA-N 2-amino-3,9-dihydropurin-9-ium-6-one;chloride Chemical compound Cl.N1C(N)=NC(=O)C2=C1N=CN2 IBAOFQIOOBQLHE-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000000840 anti-viral effect Effects 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 5
- CQYPNVKLVHHOSJ-UHFFFAOYSA-N 6-iodo-7h-purin-2-amine Chemical compound NC1=NC(I)=C2NC=NC2=N1 CQYPNVKLVHHOSJ-UHFFFAOYSA-N 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 150000003212 purines Chemical class 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- GRDWUAJVJQKXCX-UHFFFAOYSA-N 2-propan-2-yl-1,3-dioxane-5,5-dicarboxylic acid Chemical compound CC(C)C1OCC(C(O)=O)(C(O)=O)CO1 GRDWUAJVJQKXCX-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 125000002015 acyclic group Chemical group 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- HDGHQFQMWUTHKL-UHFFFAOYSA-N 2-methyl-1,3-dioxane Chemical compound CC1OCCCO1 HDGHQFQMWUTHKL-UHFFFAOYSA-N 0.000 description 3
- LAMFNZWIXHJCMW-UHFFFAOYSA-N 2-propan-2-yl-1,3-dioxane-5-carboxylic acid Chemical compound CC(C)C1OCC(C(O)=O)CO1 LAMFNZWIXHJCMW-UHFFFAOYSA-N 0.000 description 3
- IEIXTBVFNVLXQP-UHFFFAOYSA-N 6-chloro-9-[(2-propan-2-yl-1,3-dioxan-5-yl)methyl]purin-2-amine Chemical compound C1OC(C(C)C)OCC1CN1C2=NC(N)=NC(Cl)=C2N=C1 IEIXTBVFNVLXQP-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- GMFFYZCHSYHKLM-UHFFFAOYSA-N [2-(acetyloxymethyl)-3-hydroxypropyl] acetate Chemical compound CC(=O)OCC(CO)COC(C)=O GMFFYZCHSYHKLM-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- ZZETUFLYPMIVJC-UHFFFAOYSA-N (2-propan-2-yl-1,3-dioxan-5-yl)methanol Chemical compound CC(C)C1OCC(CO)CO1 ZZETUFLYPMIVJC-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- SFRDXVJWXWOTEW-UHFFFAOYSA-N 2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)CO SFRDXVJWXWOTEW-UHFFFAOYSA-N 0.000 description 2
- GKANYIYHVWIXIC-UHFFFAOYSA-N 2-[(2,6-diaminopurin-9-yl)methyl]propane-1,3-diol Chemical compound NC1=NC(N)=C2N=CN(CC(CO)CO)C2=N1 GKANYIYHVWIXIC-UHFFFAOYSA-N 0.000 description 2
- NWZYKJBQUDRPIW-UHFFFAOYSA-N 2-[(2-amino-6-iodopurin-9-yl)methyl]propane-1,3-diol Chemical compound NC1=NC(I)=C2N=CN(CC(CO)CO)C2=N1 NWZYKJBQUDRPIW-UHFFFAOYSA-N 0.000 description 2
- BPVHBSUJEOMRDH-UHFFFAOYSA-N 2-amino-1,7-dihydropurine-3,9-diium-6-one dichloride Chemical compound Cl.Cl.O=C1NC(N)=NC2=C1NC=N2 BPVHBSUJEOMRDH-UHFFFAOYSA-N 0.000 description 2
- PFPGWAOSFQGOOR-UHFFFAOYSA-N 2-ethyl-2-propan-2-yl-1,3-dioxane-5,5-dicarboxylic acid Chemical compound CCC1(C(C)C)OCC(C(O)=O)(C(O)=O)CO1 PFPGWAOSFQGOOR-UHFFFAOYSA-N 0.000 description 2
- HJKGBRPNSJADMB-UHFFFAOYSA-N 3-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CN=C1 HJKGBRPNSJADMB-UHFFFAOYSA-N 0.000 description 2
- JVZRCNQLWOELDU-UHFFFAOYSA-N 4-Phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 description 2
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- GJAARPKBDFKHFS-UHFFFAOYSA-N Gerin Natural products COC(=O)C(=C)C1CC2C(=C)C(=O)C=CC2(C)CC1OC(=O)C GJAARPKBDFKHFS-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- NKHRVXRAZFKVLT-UHFFFAOYSA-N [2-(acetyloxymethyl)-3-(2-amino-6-iodopurin-9-yl)propyl] acetate Chemical compound N1=C(N)N=C2N(CC(COC(C)=O)COC(=O)C)C=NC2=C1I NKHRVXRAZFKVLT-UHFFFAOYSA-N 0.000 description 2
- HNTVAEXKUGHEEK-UHFFFAOYSA-N [2-(acetyloxymethyl)-3-(2-amino-6-oxo-3h-purin-9-yl)propyl] acetate Chemical compound N1C(N)=NC(=O)C2=C1N(CC(COC(C)=O)COC(=O)C)C=N2 HNTVAEXKUGHEEK-UHFFFAOYSA-N 0.000 description 2
- MBHOGCXKMGIEIL-UHFFFAOYSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methyl]-3-hydroxypropyl] acetate Chemical compound N1C(N)=NC(=O)C2=C1N(CC(CO)COC(=O)C)C=N2 MBHOGCXKMGIEIL-UHFFFAOYSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
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- 229910052698 phosphorus Inorganic materials 0.000 description 1
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- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 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
- 239000012265 solid product Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
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- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
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- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- AGZPNUZBDCYTBB-UHFFFAOYSA-N triethyl methanetricarboxylate Chemical compound CCOC(=O)C(C(=O)OCC)C(=O)OCC AGZPNUZBDCYTBB-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
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
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- 239000008215 water for injection Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/36—Sulfur atom
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU9129 | 1997-09-11 | ||
| AUPO9129A AUPO912997A0 (en) | 1997-09-11 | 1997-09-11 | Antiviral agents |
| PCT/AU1998/000748 WO1999012927A1 (en) | 1997-09-11 | 1998-09-11 | Purine acyclonucleosides as antiviral agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001515900A true JP2001515900A (ja) | 2001-09-25 |
Family
ID=3803414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000510734A Withdrawn JP2001515900A (ja) | 1997-09-11 | 1998-09-11 | 抗ウイルス薬 |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1019404A4 (zh) |
| JP (1) | JP2001515900A (zh) |
| KR (1) | KR20010023890A (zh) |
| CN (1) | CN1269801A (zh) |
| AU (1) | AUPO912997A0 (zh) |
| CA (1) | CA2302630A1 (zh) |
| ID (1) | ID26937A (zh) |
| NZ (1) | NZ502994A (zh) |
| WO (1) | WO1999012927A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022050632A (ja) * | 2016-08-29 | 2022-03-30 | エフ．ホフマン－ラ ロシュ アーゲー | ウイルス感染の治療又は予防用の７位置換スルホンイミドイルプリノン化合物 |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI20022A (sl) * | 1998-07-29 | 2000-02-29 | Kemijski inštitut | Alkilno substituirani purinovi derivati in njihova priprava |
| KR100377138B1 (ko) * | 1998-11-10 | 2003-06-12 | 주식회사 엘지생명과학 | 퓨린구조를갖는싸이클린의존키나아제저해제,그제조방법및그를함유하는항암제조성물 |
| GB9903762D0 (en) | 1999-02-18 | 1999-04-14 | Novartis Ag | Organic compounds |
| AU5322601A (en) * | 2000-04-07 | 2001-10-23 | Univ Maryland | Bile acid containing prodrugs with enhanced bioavailability |
| EP2336133A1 (en) | 2001-10-30 | 2011-06-22 | Conforma Therapeutics Corporation | Purine analogs having HSP90-inhibiting activity |
| DE60313173T2 (de) * | 2002-06-27 | 2008-01-03 | F. Hoffmann-La Roche Ag | Synthese von purin-derivaten |
| US20060128956A1 (en) * | 2003-04-21 | 2006-06-15 | Ustav Organicke Chemie A Biochemie Akademie Ved Ceske Republiky | (Purin-6-yl) amino acid and production method thereof |
| EA010160B1 (ru) | 2003-09-18 | 2008-06-30 | Конформа Терапьютикс Корпорейшн | Новые гетероциклические соединения - ингибиторы hsp90 и способы их получения |
| NZ561939A (en) | 2005-03-30 | 2011-03-31 | Conforma Therapeutics Corp | Alkynyl pyrrolopyrimidines and related analogs as HSP90-inhibitors |
| CN102002043B (zh) * | 2010-11-16 | 2012-10-24 | 江苏科技大学 | 4-氨基吡啶催化下的6-甲氧基嘌呤衍生物的合成方法 |
| CN102633767B (zh) * | 2012-04-09 | 2013-10-30 | 武汉工程大学 | 一种非离子型碘造影剂中间体2－异丙基－5－羧基－1，3－二氧六环的制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5216141A (en) * | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| GB8904855D0 (en) * | 1989-03-03 | 1989-04-12 | Beecham Group Plc | Pharmaceutical treatment |
-
1997
- 1997-09-11 AU AUPO9129A patent/AUPO912997A0/en not_active Abandoned
-
1998
- 1998-09-11 CN CN98809019A patent/CN1269801A/zh active Pending
- 1998-09-11 JP JP2000510734A patent/JP2001515900A/ja not_active Withdrawn
- 1998-09-11 NZ NZ502994A patent/NZ502994A/en unknown
- 1998-09-11 KR KR1020007002574A patent/KR20010023890A/ko not_active Application Discontinuation
- 1998-09-11 ID IDW20000441A patent/ID26937A/id unknown
- 1998-09-11 EP EP98942377A patent/EP1019404A4/en not_active Withdrawn
- 1998-09-11 WO PCT/AU1998/000748 patent/WO1999012927A1/en not_active Application Discontinuation
- 1998-09-11 CA CA002302630A patent/CA2302630A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022050632A (ja) * | 2016-08-29 | 2022-03-30 | エフ．ホフマン－ラ ロシュ アーゲー | ウイルス感染の治療又は予防用の７位置換スルホンイミドイルプリノン化合物 |
| JP7214900B2 (ja) | 2016-08-29 | 2023-01-30 | エフ．ホフマン－ラ ロシュ アーゲー | ウイルス感染の治療又は予防用の７位置換スルホンイミドイルプリノン化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999012927A1 (en) | 1999-03-18 |
| CA2302630A1 (en) | 1999-03-18 |
| NZ502994A (en) | 2001-12-21 |
| EP1019404A1 (en) | 2000-07-19 |
| AUPO912997A0 (en) | 1997-10-02 |
| KR20010023890A (ko) | 2001-03-26 |
| CN1269801A (zh) | 2000-10-11 |
| ID26937A (id) | 2001-02-22 |
| EP1019404A4 (en) | 2001-07-04 |
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