CH553805A - Verfahren zur herstellung von neuen purinderivaten. - Google Patents
Verfahren zur herstellung von neuen purinderivaten.Info
- Publication number
- CH553805A CH553805A CH1266369A CH1266369A CH553805A CH 553805 A CH553805 A CH 553805A CH 1266369 A CH1266369 A CH 1266369A CH 1266369 A CH1266369 A CH 1266369A CH 553805 A CH553805 A CH 553805A
- Authority
- CH
- Switzerland
- Prior art keywords
- deoxy
- acid
- aminopurin
- group
- erythronic
- Prior art date
Links
- -1 Purinyl hydroxy Chemical group 0.000 title claims abstract description 128
- 239000002253 acid Substances 0.000 title abstract description 13
- 239000003529 anticholesteremic agent Substances 0.000 title abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
- 125000001118 alkylidene group Chemical group 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000002252 acyl group Chemical group 0.000 claims abstract 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- 150000003212 purines Chemical class 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 14
- 230000002378 acidificating effect Effects 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 9
- 235000019253 formic acid Nutrition 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- HDFRDWFLWVCOGP-UHFFFAOYSA-N carbonothioic O,S-acid Chemical class OC(S)=O HDFRDWFLWVCOGP-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000012736 aqueous medium Substances 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 2
- 150000005840 aryl radicals Chemical class 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- FSIVLXOZVUZNLN-RNFRBKRXSA-N (2R,3R)-2,3-dihydroxy-4-purin-9-ylbutanoic acid Chemical class N1=CN=C2N(C=NC2=C1)C[C@H]([C@H](C(=O)O)O)O FSIVLXOZVUZNLN-RNFRBKRXSA-N 0.000 abstract description 4
- 150000001408 amides Chemical class 0.000 abstract description 2
- 150000002148 esters Chemical class 0.000 abstract description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- 238000002844 melting Methods 0.000 description 72
- 230000008018 melting Effects 0.000 description 72
- 238000000354 decomposition reaction Methods 0.000 description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
- 239000000243 solution Substances 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000013078 crystal Substances 0.000 description 32
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 238000001914 filtration Methods 0.000 description 20
- 239000000725 suspension Substances 0.000 description 15
- 235000011054 acetic acid Nutrition 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- LIEMBEWXEZJEEZ-INEUFUBQSA-N (2r,3r)-4-(6-aminopurin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound NC1=NC=NC2=C1N=CN2C[C@@H](O)[C@@H](O)C(O)=O LIEMBEWXEZJEEZ-INEUFUBQSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 9
- LOUGYXZSURQALL-PWNYCUMCSA-N 4-Deoxyerythronic acid Chemical compound C[C@@H](O)[C@@H](O)C(O)=O LOUGYXZSURQALL-PWNYCUMCSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000003456 ion exchange resin Substances 0.000 description 9
- 229920003303 ion-exchange polymer Polymers 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 238000002211 ultraviolet spectrum Methods 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- DQSWNDKQONYEFS-IYSWYEEDSA-N methyl (2r,3r)-4-(6-aminopurin-9-yl)-2,3-dihydroxybutanoate Chemical compound N1=CN=C2N(C[C@@H](O)[C@@H](O)C(=O)OC)C=NC2=C1N DQSWNDKQONYEFS-IYSWYEEDSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- AAIRDYZWIJOQMA-INEUFUBQSA-N (2R,3R)-2,3-dihydroxy-4-(6-oxo-1H-purin-9-yl)butanoic acid Chemical compound OC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O AAIRDYZWIJOQMA-INEUFUBQSA-N 0.000 description 4
- YUBRXZMZBCPJJE-INEUFUBQSA-N (2R,3R)-2,3-dihydroxy-4-(6-sulfanylidene-3H-purin-9-yl)butanoic acid Chemical compound SC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O YUBRXZMZBCPJJE-INEUFUBQSA-N 0.000 description 4
- RTMQGJMDHYGRED-NQXXGFSBSA-N (2R,3R)-4-(2-amino-6-oxo-1H-purin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound NC1=NC(=C2N=CN(C2=N1)C[C@H]([C@H](C(=O)O)O)O)O RTMQGJMDHYGRED-NQXXGFSBSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- RSQHXZQEKJLBGP-IYSWYEEDSA-N NC1=C2N=C(N(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)C Chemical compound NC1=C2N=C(N(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)C RSQHXZQEKJLBGP-IYSWYEEDSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- YUYPXUYQOGLZEM-IYSWYEEDSA-N (2R,3R)-2,3-dihydroxy-4-(6-methylsulfanylpurin-9-yl)butanoic acid Chemical compound CSC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O YUYPXUYQOGLZEM-IYSWYEEDSA-N 0.000 description 3
- SFBMYCRIJXWGED-INEUFUBQSA-N (2R,3R)-2,3-dihydroxy-4-[6-(hydroxyamino)purin-9-yl]butanoic acid Chemical compound ONC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O SFBMYCRIJXWGED-INEUFUBQSA-N 0.000 description 3
- XFIDLFXIHFLUKL-INEUFUBQSA-N (2R,3R)-4-(6-aminopurin-9-yl)-2,3-dihydroxybutanamide Chemical compound NC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)N)O)O XFIDLFXIHFLUKL-INEUFUBQSA-N 0.000 description 3
- DDWDIPZUQCFVDA-HTRCEHHLSA-N (2R,3R)-4-(6-aminopurin-9-yl)-N-ethyl-2,3-dihydroxybutanamide Chemical compound C(C)NC(=O)[C@H](O)[C@H](O)CN1C2=NC=NC(=C2N=C1)N DDWDIPZUQCFVDA-HTRCEHHLSA-N 0.000 description 3
- AARJUJLMGBKEBA-INEUFUBQSA-N (2R,3R)-4-(6-chloropurin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound ClC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O AARJUJLMGBKEBA-INEUFUBQSA-N 0.000 description 3
- KMEDBJNRJKROEO-PSASIEDQSA-N (2R,3R)-4-[6-(diethylamino)purin-9-yl]-2,3-dihydroxybutanoic acid Chemical compound C(C)N(C1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)CC KMEDBJNRJKROEO-PSASIEDQSA-N 0.000 description 3
- RGOSMXWHVBPCHO-HTRCEHHLSA-N (2R,3R)-4-[6-(ethylamino)purin-9-yl]-2,3-dihydroxybutanoic acid Chemical compound C(C)NC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O RGOSMXWHVBPCHO-HTRCEHHLSA-N 0.000 description 3
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical group ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 3
- BWLOHIMQWHFSQF-UHFFFAOYSA-N 6-chloro-5-nitropyrimidin-4-amine Chemical compound NC1=NC=NC(Cl)=C1[N+]([O-])=O BWLOHIMQWHFSQF-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XIEXEBZGBRNYJD-PHDIDXHHSA-N C(C)(C)=C([C@H]([C@H](C(=O)O)O)O)O Chemical compound C(C)(C)=C([C@H]([C@H](C(=O)O)O)O)O XIEXEBZGBRNYJD-PHDIDXHHSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- PNJFAFCNVQBRBU-NQXXGFSBSA-N NC1=C2N=C(N(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)S Chemical compound NC1=C2N=C(N(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)S PNJFAFCNVQBRBU-NQXXGFSBSA-N 0.000 description 3
- IQWJARHUKQVCCD-UHFFFAOYSA-N NC1=C2N=CN(C2=NC=[N+]1[O-])CC(C(O)C(=O)O)O Chemical compound NC1=C2N=CN(C2=NC=[N+]1[O-])CC(C(O)C(=O)O)O IQWJARHUKQVCCD-UHFFFAOYSA-N 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- JEGDCGQQNAIPRE-HTRCEHHLSA-N ethyl (2R,3R)-4-(6-aminopurin-9-yl)-2,3-dihydroxybutanoate Chemical compound NC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)OCC)O)O JEGDCGQQNAIPRE-HTRCEHHLSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- GAPYKZAARZMMGP-UHFFFAOYSA-N pyridin-1-ium;acetate Chemical compound CC(O)=O.C1=CC=NC=C1 GAPYKZAARZMMGP-UHFFFAOYSA-N 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- VLLBJQDHHBYGAX-INEUFUBQSA-N (2R,3R)-2,3-dihydroxy-4-(6-oxo-1H-purin-9-yl)butanamide Chemical compound OC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)N)O)O VLLBJQDHHBYGAX-INEUFUBQSA-N 0.000 description 2
- FVMQTOFYJDKVQT-NQXXGFSBSA-N (2R,3R)-4-(2,6-dioxo-3H-purin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound OC1=NC(=C2N=CN(C2=N1)C[C@H]([C@H](C(=O)O)O)O)O FVMQTOFYJDKVQT-NQXXGFSBSA-N 0.000 description 2
- SADDDIMVZXRAQS-PHDIDXHHSA-N (2R,3R)-4-(2-aminopurin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound NC1=NC=C2N=CN(C2=N1)C[C@H]([C@H](C(=O)O)O)O SADDDIMVZXRAQS-PHDIDXHHSA-N 0.000 description 2
- RNINYHJCQYRBSF-NQXXGFSBSA-N (2R,3R)-4-(6,8-diaminopurin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound NC1=C2N=C(N(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)N RNINYHJCQYRBSF-NQXXGFSBSA-N 0.000 description 2
- COXHRCNSTNCRRT-NQXXGFSBSA-N (2R,3R)-4-(6,8-dioxo-1,7-dihydropurin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound OC1=C2N=C(N(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)O COXHRCNSTNCRRT-NQXXGFSBSA-N 0.000 description 2
- SYJJGXMNDOCGJI-NQXXGFSBSA-N (2R,3R)-4-(6-amino-8-oxo-7H-purin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound NC1=C2N=C(N(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O)O SYJJGXMNDOCGJI-NQXXGFSBSA-N 0.000 description 2
- IVZVKPSDZGBOMS-ZYHUDNBSSA-N (2R,3R)-4-(6-benzamidopurin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound C(C1=CC=CC=C1)(=O)NC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O IVZVKPSDZGBOMS-ZYHUDNBSSA-N 0.000 description 2
- GAKZPWFHHWRPQS-PHDIDXHHSA-N (2R,3R)-4-(8-aminopurin-9-yl)-2,3-dihydroxybutanoic acid Chemical compound NC=1N(C2=NC=NC=C2N1)C[C@H]([C@H](C(=O)O)O)O GAKZPWFHHWRPQS-PHDIDXHHSA-N 0.000 description 2
- HVLSERFWORQCLL-DGCLKSJQSA-N (2R,3R)-4-[6-(benzylamino)purin-9-yl]-2,3-dihydroxybutanoic acid Chemical compound C(C1=CC=CC=C1)NC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)O)O)O HVLSERFWORQCLL-DGCLKSJQSA-N 0.000 description 2
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- QNGFMNQJXGHSAG-KSBSHMNSSA-N CC[C@@]([C@@H](CN1C2=NC=NC(N)=C2N=C1)O)(C(O)=O)O Chemical compound CC[C@@]([C@@H](CN1C2=NC=NC(N)=C2N=C1)O)(C(O)=O)O QNGFMNQJXGHSAG-KSBSHMNSSA-N 0.000 description 2
- SEZIUTHZDBJOBF-INEUFUBQSA-N CSC1=NC(=C2N=CN(C2=N1)C[C@H]([C@H](C(=O)O)O)O)N Chemical compound CSC1=NC(=C2N=CN(C2=N1)C[C@H]([C@H](C(=O)O)O)O)N SEZIUTHZDBJOBF-INEUFUBQSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
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- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- HJSMLDVJDUBCLQ-UHFFFAOYSA-N diethoxymethanethione Chemical compound CCOC(=S)OCC HJSMLDVJDUBCLQ-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- BJIKOZOULYUROB-UHFFFAOYSA-N dimethoxymethanethione Chemical compound COC(=S)OC BJIKOZOULYUROB-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- RMQUTIUKCXKCJM-MWLCHTKSSA-N methyl (2R,3R)-2,3-diacetyloxy-4-(6-aminopurin-9-yl)butanoate Chemical compound NC1=C2N=CN(C2=NC=N1)C[C@H]([C@H](C(=O)OC)OC(C)=O)OC(C)=O RMQUTIUKCXKCJM-MWLCHTKSSA-N 0.000 description 1
- UAZBCJNWJSYVMI-IYSWYEEDSA-N methyl (2R,3R)-2,3-dihydroxy-4-(6-oxo-1H-purin-9-yl)butanoate Chemical compound COC(=O)[C@H](O)[C@H](O)CN1C2=NC=NC(=C2N=C1)O UAZBCJNWJSYVMI-IYSWYEEDSA-N 0.000 description 1
- DDMCDMDOHABRHD-SCSAIBSYSA-N methyl (2r)-2-hydroxybutanoate Chemical compound CC[C@@H](O)C(=O)OC DDMCDMDOHABRHD-SCSAIBSYSA-N 0.000 description 1
- HNKGMGPCSSJYOT-UHFFFAOYSA-N methyl 4-(6-aminopurin-9-yl)-2-hydroxybutanoate Chemical compound N1=CN=C2N(CCC(O)C(=O)OC)C=NC2=C1N HNKGMGPCSSJYOT-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
- JVHPKYBRJQNPAT-UHFFFAOYSA-N n-cyclohexyl-2,2-diphenylethenimine Chemical compound C1CCCCC1N=C=C(C=1C=CC=CC=1)C1=CC=CC=C1 JVHPKYBRJQNPAT-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- RZFBEFUNINJXRQ-UHFFFAOYSA-M sodium ethyl xanthate Chemical compound [Na+].CCOC([S-])=S RZFBEFUNINJXRQ-UHFFFAOYSA-M 0.000 description 1
- VKLSDZKZPNFGLB-FINAUTGASA-M sodium;(2r,3r)-4-(6-aminopurin-9-yl)-2,3-dihydroxybutanoate Chemical compound [Na+].NC1=NC=NC2=C1N=CN2C[C@@H](O)[C@@H](O)C([O-])=O VKLSDZKZPNFGLB-FINAUTGASA-M 0.000 description 1
- QZNVHCWSDFYKTO-UHFFFAOYSA-M sodium;methanedithioate Chemical compound [Na+].[S-]C=S QZNVHCWSDFYKTO-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 230000035901 vesication Effects 0.000 description 1
Classifications
-
- 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
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2284969 | 1969-03-25 | ||
| JP2284669 | 1969-03-25 | ||
| JP2284769 | 1969-03-25 | ||
| JP2284869 | 1969-03-25 | ||
| JP2459869 | 1969-03-31 | ||
| JP3058969 | 1969-04-18 | ||
| JP3058869 | 1969-04-18 | ||
| JP3058369 | 1969-04-18 | ||
| JP3058769 | 1969-04-18 | ||
| JP3058669 | 1969-04-18 | ||
| JP3058469 | 1969-04-18 | ||
| JP3058569 | 1969-04-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH553805A true CH553805A (de) | 1974-09-13 |
Family
ID=27583212
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1266369A CH553805A (de) | 1969-03-25 | 1969-08-20 | Verfahren zur herstellung von neuen purinderivaten. |
Country Status (4)
-
1969
- 1969-08-18 NO NO333969A patent/NO129679B/no unknown
- 1969-08-19 HU HUFU000275 patent/HU165535B/hu unknown
- 1969-08-19 CA CA059,962A patent/CA983490A/en not_active Expired
- 1969-08-20 CH CH1266369A patent/CH553805A/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HU165535B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1974-09-28 |
| NO129679B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1974-05-13 |
| CA983490A (en) | 1976-02-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |