HU193874B - Process for preparing substituted 9-(1- or 3-monoacyloxy- or 1,3-diacyloxy-2-propoxymethyl)-purine derivatives and pharmaceuticals comprising such compounds - Google Patents
Process for preparing substituted 9-(1- or 3-monoacyloxy- or 1,3-diacyloxy-2-propoxymethyl)-purine derivatives and pharmaceuticals comprising such compounds Download PDFInfo
- Publication number
- HU193874B HU193874B HU83314A HU31483A HU193874B HU 193874 B HU193874 B HU 193874B HU 83314 A HU83314 A HU 83314A HU 31483 A HU31483 A HU 31483A HU 193874 B HU193874 B HU 193874B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- compound
- propoxymethyl
- priority
- guanine
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 153
- 239000003814 drug Substances 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title claims 2
- -1 1- adamantyl Chemical group 0.000 claims abstract description 48
- 239000001257 hydrogen Substances 0.000 claims abstract description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 45
- 239000002253 acid Substances 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 5
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 37
- 239000004480 active ingredient Substances 0.000 claims description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 31
- 238000002360 preparation method Methods 0.000 claims description 29
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 28
- 230000008569 process Effects 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 16
- 241000700605 Viruses Species 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 229960000583 acetic acid Drugs 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
- 239000012362 glacial acetic acid Substances 0.000 claims description 9
- 230000000840 anti-viral effect Effects 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 208000009889 Herpes Simplex Diseases 0.000 claims description 4
- PJWVIYVXUNFHQK-UHFFFAOYSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]-3-(2,2-dimethylpropanoyloxy)propyl] 2,2-dimethylpropanoate Chemical group N1=C(N)NC(=O)C2=C1N(COC(COC(=O)C(C)(C)C)COC(=O)C(C)(C)C)C=N2 PJWVIYVXUNFHQK-UHFFFAOYSA-N 0.000 claims description 4
- MNOWAMSYLDJFFI-UHFFFAOYSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]-3-hexadecanoyloxypropyl] hexadecanoate Chemical group N1=C(N)NC(=O)C2=C1N(COC(COC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC)C=N2 MNOWAMSYLDJFFI-UHFFFAOYSA-N 0.000 claims description 4
- COELUGODEFADMG-UHFFFAOYSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]-3-octanoyloxypropyl] octanoate Chemical group N1=C(N)NC(=O)C2=C1N(COC(COC(=O)CCCCCCC)COC(=O)CCCCCCC)C=N2 COELUGODEFADMG-UHFFFAOYSA-N 0.000 claims description 4
- 150000008065 acid anhydrides Chemical class 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 206010019799 Hepatitis viral Diseases 0.000 claims description 3
- XITLNNHRMHUWHT-UHFFFAOYSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]-3-decanoyloxypropyl] decanoate Chemical group N1=C(N)NC(=O)C2=C1N(COC(COC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC)C=N2 XITLNNHRMHUWHT-UHFFFAOYSA-N 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 150000003573 thiols Chemical class 0.000 claims description 3
- 201000006082 Chickenpox Diseases 0.000 claims description 2
- 241000701022 Cytomegalovirus Species 0.000 claims description 2
- 208000007514 Herpes zoster Diseases 0.000 claims description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 2
- 206010046980 Varicella Diseases 0.000 claims description 2
- IUPMLNIKQBVXQC-UHFFFAOYSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]-3-pentanoyloxypropyl] pentanoate Chemical group N1=C(N)NC(=O)C2=C1N(COC(COC(=O)CCCC)COC(=O)CCCC)C=N2 IUPMLNIKQBVXQC-UHFFFAOYSA-N 0.000 claims description 2
- 201000001862 viral hepatitis Diseases 0.000 claims description 2
- 206010029897 Obsessive thoughts Diseases 0.000 claims 8
- 125000004043 oxo group Chemical group O=* 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 3
- 150000004820 halides Chemical class 0.000 claims 3
- 125000002252 acyl group Chemical group 0.000 claims 2
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 238000005520 cutting process Methods 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 10
- 125000000468 ketone group Chemical group 0.000 abstract description 8
- 229910052783 alkali metal Inorganic materials 0.000 abstract description 6
- 125000004414 alkyl thio group Chemical group 0.000 abstract description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 abstract description 3
- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 239000003443 antiviral agent Substances 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 241001529453 unidentified herpesvirus Species 0.000 description 19
- 239000002904 solvent Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 208000015181 infectious disease Diseases 0.000 description 12
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 235000011114 ammonium hydroxide Nutrition 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000000908 ammonium hydroxide Substances 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 150000005690 diesters Chemical class 0.000 description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- 208000036142 Viral infection Diseases 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 5
- 239000003380 propellant Substances 0.000 description 5
- 230000009385 viral infection Effects 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- QHHLLMASUBEZEZ-UHFFFAOYSA-N 1,3-bis(phenylmethoxy)propan-2-yloxymethyl acetate Chemical compound C=1C=CC=CC=1COCC(OCOC(=O)C)COCC1=CC=CC=C1 QHHLLMASUBEZEZ-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- OBOHMJWDFPBPKD-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 OBOHMJWDFPBPKD-UHFFFAOYSA-N 0.000 description 3
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 241000286209 Phasianidae Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NSZKHEYZLNPIEJ-UHFFFAOYSA-N [3-acetyloxy-2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]propyl] acetate Chemical compound N1C(N)=NC(=O)C2=C1N(COC(COC(C)=O)COC(=O)C)C=N2 NSZKHEYZLNPIEJ-UHFFFAOYSA-N 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
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 238000005886 esterification reaction Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 3
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 2
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- ARLSYSVVBAMYKA-UHFFFAOYSA-N 1,3-bis(phenylmethoxy)propan-2-ol Chemical compound C=1C=CC=CC=1COCC(O)COCC1=CC=CC=C1 ARLSYSVVBAMYKA-UHFFFAOYSA-N 0.000 description 2
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
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- 241000124008 Mammalia Species 0.000 description 2
- 208000006758 Marek Disease Diseases 0.000 description 2
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- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical class O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
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- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/14—Unsaturated ethers
- C07C43/178—Unsaturated ethers containing hydroxy or O-metal groups
- C07C43/1785—Unsaturated ethers containing hydroxy or O-metal groups having more than one ether bound
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/14—Unsaturated ethers
- C07C43/178—Unsaturated ethers containing hydroxy or O-metal groups
- C07C43/1786—Unsaturated ethers containing hydroxy or O-metal groups containing halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34470382A | 1982-02-01 | 1982-02-01 | |
| US07/451,262 US5250535A (en) | 1982-02-01 | 1982-12-22 | Substituted 9-(1 or 3-monoacyloxy or 1,3-diacyloxy-2-propoxymethyl) purines as antiviral agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU193874B true HU193874B (en) | 1987-12-28 |
Family
ID=26994067
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU83314A HU193874B (en) | 1982-02-01 | 1983-01-31 | Process for preparing substituted 9-(1- or 3-monoacyloxy- or 1,3-diacyloxy-2-propoxymethyl)-purine derivatives and pharmaceuticals comprising such compounds |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5250535A (enEXAMPLES) |
| EP (1) | EP0085424A3 (enEXAMPLES) |
| KR (1) | KR890000191B1 (enEXAMPLES) |
| AU (2) | AU572777B2 (enEXAMPLES) |
| BR (1) | BR8300475A (enEXAMPLES) |
| DD (1) | DD206781A5 (enEXAMPLES) |
| DK (1) | DK29183A (enEXAMPLES) |
| ES (1) | ES519423A0 (enEXAMPLES) |
| FI (1) | FI79851C (enEXAMPLES) |
| GR (1) | GR81321B (enEXAMPLES) |
| HU (1) | HU193874B (enEXAMPLES) |
| IL (1) | IL67791A0 (enEXAMPLES) |
| IN (1) | IN157856B (enEXAMPLES) |
| NO (1) | NO161372C (enEXAMPLES) |
| NZ (1) | NZ203128A (enEXAMPLES) |
| PH (5) | PH19203A (enEXAMPLES) |
| PL (1) | PL140556B1 (enEXAMPLES) |
| PT (1) | PT76149B (enEXAMPLES) |
| RO (3) | RO89143A (enEXAMPLES) |
| ZW (1) | ZW2583A1 (enEXAMPLES) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES514877A0 (es) * | 1981-08-11 | 1983-10-01 | Wellcome Found | "un procedimiento para preparar derivados de purina". |
| US4816447A (en) * | 1981-08-26 | 1989-03-28 | Merck & Co., Inc. | Anti-viral guanine compounds |
| US4544634A (en) * | 1982-10-14 | 1985-10-01 | Burroughs Wellcome Co. | Method of producing acyclovir |
| NO161116C (no) * | 1982-10-14 | 1989-07-05 | Wellcome Found | Analogifremgangsmaate for fremstilling av antiviralt virksomme purinderivater. |
| US4609662A (en) * | 1982-10-14 | 1986-09-02 | Burroughs Wellcome Co. | Method for using purine derivatives |
| US4880820A (en) * | 1983-06-24 | 1989-11-14 | Merck & Co., Inc. | Guanine derivatives |
| EP0138683A3 (en) * | 1983-09-30 | 1988-01-20 | Merck & Co. Inc. | Purine derivatives, their application in anti-viral compositions |
| US4897479A (en) * | 1983-09-30 | 1990-01-30 | Merck & Co., Inc. | Arylsulfonyloxy purine intermediates |
| IE842642L (en) * | 1983-10-31 | 1985-04-30 | Harvard College | Purine Derivatives |
| IL73682A (en) * | 1983-12-20 | 1991-08-16 | Medivir Ab | Antiviral pharmaceutical compositions containing 9-hydroxy aliphatic derivatives of guanine,some new such derivatives and process for their preparation |
| EP0152316B1 (en) * | 1984-01-26 | 1989-07-26 | Merck & Co. Inc. | Substituted butyl guanines and their utilization in antiviral compositions |
| US4579849A (en) * | 1984-04-06 | 1986-04-01 | Merck & Co., Inc. | N-alkylguanine acyclonucleosides as antiviral agents |
| WO1986000901A1 (en) * | 1984-07-20 | 1986-02-13 | Gauntt Charles O | Immunoregulatory and anti-viral compound |
| JPH075595B2 (ja) * | 1984-12-12 | 1995-01-25 | シンテツクス（ユー・エス・エイ）インコーポレイテツド | ９―（１，３―ジヒドロキシ―２―プロポキシメチル）グアニン類化合物の製法 |
| HU196607B (en) * | 1985-05-15 | 1988-12-28 | Wellcome Found | Process for producing dideoxy-nucleosides and pharmaceutics comprising such compounds |
| DE3627024A1 (de) * | 1985-09-24 | 1987-04-02 | Hoechst Ag | In 6- und 9-stellung substituierte 2-aminopurine, ihre verwendung, diese purine enthaltende arzneimittel und verfahren zur herstellung der purine |
| US4966895A (en) * | 1989-02-02 | 1990-10-30 | Merck & Co. Inc. | Cyclic monophosphates of purine and pyrimidine acyclonucleosides as anti-retroviral agents |
| US5216142A (en) * | 1989-04-17 | 1993-06-01 | Efamol Holdings Plc | Anti-virals |
| GB2260319B (en) | 1991-10-07 | 1995-12-06 | Norsk Hydro As | Acyl derivatives of nucleosides and nucleoside analogues having anti-viral activity |
| US5670506A (en) * | 1993-04-05 | 1997-09-23 | Cell Therapeutics, Inc. | Halogen, isothiocyanate or azide substituted xanthines |
| US5565565A (en) | 1994-08-04 | 1996-10-15 | Syntex (U.S.A.) Inc. | Preparation of N-9 substituted guanine compounds |
| US6060477A (en) * | 1995-06-07 | 2000-05-09 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl cycloamino pyrimidinone derivatives |
| US6200980B1 (en) | 1995-06-07 | 2001-03-13 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl purinone derivatives |
| US6046216A (en) * | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl pyridinone derivatives |
| US5874440A (en) * | 1995-06-07 | 1999-02-23 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with phenyl pyrimidinone derivatives |
| US6046206A (en) * | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having a precancerous lesions with amide quinazoline derivatives |
| US6232312B1 (en) | 1995-06-07 | 2001-05-15 | Cell Pathways, Inc. | Method for treating patient having precancerous lesions with a combination of pyrimidopyrimidine derivatives and esters and amides of substituted indenyl acetic acides |
| US6262059B1 (en) | 1995-06-07 | 2001-07-17 | Cell Pathways, Inc. | Method of treating a patient having precancerous lesions with quinazoline derivatives |
| US5840890A (en) * | 1996-01-26 | 1998-11-24 | Syntex (U.S.A.) Inc. | Process for preparing a 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol derivative |
| CA2238283C (en) * | 1997-05-30 | 2002-08-20 | Cell Pathways, Inc. | Method for identifying compounds for inhibition of neoplastic lesions, pharmaceutical compositions from such compounds and uses of such compounds and compositions for treating neoplastic lesions |
| US5858694A (en) * | 1997-05-30 | 1999-01-12 | Cell Pathways, Inc. | Method for identifying compounds for inhibition of cancerous lesions |
| US5852035A (en) * | 1997-12-12 | 1998-12-22 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to substituted N- arylmethyl and heterocyclmethyl-1H-pyrazolo (3,4-B) quinolin-4-amines |
| US6410584B1 (en) * | 1998-01-14 | 2002-06-25 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells with indole derivatives |
| US6046199A (en) * | 1998-01-14 | 2000-04-04 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with tetracyclic pyrido[3,4-B]indole derivatives |
| US5942520A (en) * | 1998-01-27 | 1999-08-24 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells by exposure to substituted N-cycloalkylmethyl-1-H-pyrazolo (3,4-B) quinolone-4 amines |
| US5990117A (en) * | 1998-04-15 | 1999-11-23 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to quinazoline derivatives |
| US6180629B1 (en) | 1998-08-14 | 2001-01-30 | Cell Pathways, Inc. | [4,5]-Fused-1,3-disubstituted-1,2-diazine-6-one derivatives with nitrogen containing substitutents in position one for the treatment of neoplasia |
| US6268372B1 (en) | 1998-09-11 | 2001-07-31 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to 2,9-disubstituted purin-6-ones |
| US6124303A (en) * | 1998-09-11 | 2000-09-26 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to 9-substituted 2-(2-N-aloxyphenyl) purin-6-ones |
| US6200771B1 (en) | 1998-10-15 | 2001-03-13 | Cell Pathways, Inc. | Method of using a novel phosphodiesterase in pharmaceutical screeing to identify compounds for treatment of neoplasia |
| US6130053A (en) * | 1999-08-03 | 2000-10-10 | Cell Pathways, Inc. | Method for selecting compounds for inhibition of neoplastic lesions |
| US6133271A (en) * | 1998-11-19 | 2000-10-17 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure thienopyrimidine derivatives |
| US6187779B1 (en) | 1998-11-20 | 2001-02-13 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells and related conditions by exposure to 2,8-disubstituted quinazoline derivatives |
| US6369092B1 (en) | 1998-11-23 | 2002-04-09 | Cell Pathways, Inc. | Method for treating neoplasia by exposure to substituted benzimidazole derivatives |
| US6077842A (en) * | 1998-11-24 | 2000-06-20 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with pyrazolopyridylpyridazinone derivatives |
| US6486155B1 (en) | 1998-11-24 | 2002-11-26 | Cell Pathways Inc | Method of inhibiting neoplastic cells with isoquinoline derivatives |
| US6034099A (en) * | 1998-11-24 | 2000-03-07 | Cell Pathways, Inc. | Method for inhibiting neoplastic lesions by administering 4-(arylmethylene)- 2, 3- dihydro-pyrazol-3-ones |
| US6025394A (en) | 1999-01-29 | 2000-02-15 | Cell Pathways, Inc. | Method for treating patients with acne by administering substituted sulfonyl indenyl acetic acids, amides and alcohols |
| US6020379A (en) * | 1999-02-19 | 2000-02-01 | Cell Pathways, Inc. | Position 7 substituted indenyl-3-acetic acid derivatives and amides thereof for the treatment of neoplasia |
| US6555547B1 (en) | 2000-02-28 | 2003-04-29 | Cell Pathways, Inc. | Method for treating a patient with neoplasia by treatment with a vinca alkaloid derivative |
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| GB0708258D0 (en) * | 2007-04-27 | 2007-06-06 | Katholleke Universiteit Leuven | New anti-viral nulceoside analogs |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4199574A (en) * | 1974-09-02 | 1980-04-22 | Burroughs Wellcome Co. | Methods and compositions for treating viral infections and guanine acyclic nucleosides |
| GB1523865A (en) * | 1974-09-02 | 1978-09-06 | Wellcome Found | Purine compunds and salts thereof |
| US4347360A (en) * | 1980-09-16 | 1982-08-31 | Ens Bio Logicals Inc. | Ring open nucleoside analogues |
| US4355032B2 (en) * | 1981-05-21 | 1990-10-30 | 9-(1,3-dihydroxy-2-propoxymethyl)guanine as antiviral agent | |
| ES514877A0 (es) * | 1981-08-11 | 1983-10-01 | Wellcome Found | "un procedimiento para preparar derivados de purina". |
| NZ201662A (en) * | 1981-08-26 | 1986-07-11 | Merck & Co Inc | 9-(1,3-(and 2,3)-dihydroxy-1-(and 2)-propoxy-methyl)guanine derivatives and methods for their preparation |
| US4816447A (en) * | 1981-08-26 | 1989-03-28 | Merck & Co., Inc. | Anti-viral guanine compounds |
-
1982
- 1982-12-22 US US07/451,262 patent/US5250535A/en not_active Expired - Fee Related
-
1983
- 1983-01-25 DK DK29183A patent/DK29183A/da not_active Application Discontinuation
- 1983-01-26 FI FI830254A patent/FI79851C/fi not_active IP Right Cessation
- 1983-01-27 PT PT76149A patent/PT76149B/pt unknown
- 1983-01-27 PH PH28429A patent/PH19203A/en unknown
- 1983-01-31 KR KR1019830000360A patent/KR890000191B1/ko not_active Expired
- 1983-01-31 PL PL1983240367A patent/PL140556B1/pl unknown
- 1983-01-31 RO RO83114876A patent/RO89143A/ro unknown
- 1983-01-31 IL IL67791A patent/IL67791A0/xx unknown
- 1983-01-31 RO RO109871A patent/RO86234B/ro unknown
- 1983-01-31 ES ES519423A patent/ES519423A0/es active Granted
- 1983-01-31 GR GR70365A patent/GR81321B/el unknown
- 1983-01-31 HU HU83314A patent/HU193874B/hu not_active IP Right Cessation
- 1983-01-31 RO RO83114877A patent/RO89142A/ro unknown
- 1983-01-31 NO NO830316A patent/NO161372C/no unknown
- 1983-01-31 BR BR8300475A patent/BR8300475A/pt unknown
- 1983-01-31 DD DD83247593A patent/DD206781A5/de not_active IP Right Cessation
- 1983-01-31 NZ NZ203128A patent/NZ203128A/en unknown
- 1983-01-31 IN IN113/CAL/83A patent/IN157856B/en unknown
- 1983-01-31 EP EP83100886A patent/EP0085424A3/en not_active Withdrawn
- 1983-01-31 ZW ZW25/83A patent/ZW2583A1/xx unknown
- 1983-02-01 AU AU10961/83A patent/AU572777B2/en not_active Ceased
-
1984
- 1984-06-19 PH PH30839A patent/PH20099A/en unknown
- 1984-06-19 PH PH30840A patent/PH20360A/en unknown
- 1984-06-19 PH PH30841A patent/PH22817A/en unknown
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1985
- 1985-05-13 PH PH32259A patent/PH22824A/en unknown
-
1988
- 1988-03-03 AU AU12614/88A patent/AU1261488A/en not_active Withdrawn
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |