FI117673B - Nukleosidimonofosfaattijohdannaiset, niiden valmistus ja käyttö immuunivastetta heikentävien lääkkeiden valmistukseen - Google Patents

Nukleosidimonofosfaattijohdannaiset, niiden valmistus ja käyttö immuunivastetta heikentävien lääkkeiden valmistukseen Download PDF

Info

Publication number: FI117673B
Authority: FI; Finland
Prior art keywords: eller; alkyl; halogen; hydroxy; med
Prior art date: 1994-05-28

Application number

FI964727A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI964727A0 (fi

FI964727L (fi

Inventor

Alfred Mertens

Dieter Herrmann

Harald Zilch

Hans-Georg Opitz

Original Assignee

Heidelberg Pharma Holding Gmbh

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1994-05-28

Filing date

1996-11-27

Publication date

2007-01-15

1996-11-27 Application filed by Heidelberg Pharma Holding Gmbh filed Critical Heidelberg Pharma Holding Gmbh

1996-11-27 Publication of FI964727A0 publication Critical patent/FI964727A0/fi

1996-11-27 Publication of FI964727L publication Critical patent/FI964727L/fi

2007-01-15 Application granted granted Critical

2007-01-15 Publication of FI117673B publication Critical patent/FI117673B/fi

Links

-1 Nucleoside Monophosphate Chemical class 0.000 title claims abstract description 56
239000002777 nucleoside Substances 0.000 title claims abstract description 28
238000002360 preparation method Methods 0.000 title claims abstract description 13
239000003018 immunosuppressive agent Substances 0.000 title description 2
229940124589 immunosuppressive drug Drugs 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 42
239000001257 hydrogen Substances 0.000 claims abstract description 30
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
125000000217 alkyl group Chemical group 0.000 claims abstract description 24
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 10
239000003814 drug Substances 0.000 claims abstract description 9
150000003839 salts Chemical class 0.000 claims abstract description 8
238000000034 method Methods 0.000 claims abstract description 6
229920006395 saturated elastomer Polymers 0.000 claims abstract description 6
150000007522 mineralic acids Chemical class 0.000 claims abstract description 4
150000007524 organic acids Chemical class 0.000 claims abstract description 4
235000005985 organic acids Nutrition 0.000 claims abstract description 4
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 4
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 40
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 37
229910052736 halogen Inorganic materials 0.000 claims description 27
150000002367 halogens Chemical group 0.000 claims description 27
FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 claims description 24
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
125000003277 amino group Chemical group 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 10
238000011282 treatment Methods 0.000 claims description 10
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
150000003833 nucleoside derivatives Chemical class 0.000 claims description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
125000001072 heteroaryl group Chemical group 0.000 claims description 7
UEJHQHNFRZXWRD-UAKXSSHOSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 UEJHQHNFRZXWRD-UAKXSSHOSA-N 0.000 claims description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 6
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
JAPYIBBSTJFDAK-UHFFFAOYSA-N 2,4,6-tri(propan-2-yl)benzenesulfonyl chloride Chemical compound CC(C)C1=CC(C(C)C)=C(S(Cl)(=O)=O)C(C(C)C)=C1 JAPYIBBSTJFDAK-UHFFFAOYSA-N 0.000 claims description 5
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 5
206010028980 Neoplasm Diseases 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
239000000203 mixture Substances 0.000 claims description 5
125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
229920002554 vinyl polymer Polymers 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 4
LDCUBKKZHSYQTJ-UAKXSSHOSA-N 5-chloro-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Cl)=C1 LDCUBKKZHSYQTJ-UAKXSSHOSA-N 0.000 claims description 4
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
239000012442 inert solvent Substances 0.000 claims description 4
VHTXRUOQNZDVPO-TURQNECASA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-2-enylpyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(CC=C)=C1 VHTXRUOQNZDVPO-TURQNECASA-N 0.000 claims description 3
HBUBKKRHXORPQB-UUOKFMHZSA-N 2-fluoroadenosine Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HBUBKKRHXORPQB-UUOKFMHZSA-N 0.000 claims description 3
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims description 3
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims description 3
102000011420 Phospholipase D Human genes 0.000 claims description 3
108090000553 Phospholipase D Proteins 0.000 claims description 3
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
239000000872 buffer Substances 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
229940029575 guanosine Drugs 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 3
125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
VAALWQXPFZVPFE-TURQNECASA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-enylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C=CC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 VAALWQXPFZVPFE-TURQNECASA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 2
238000006243 chemical reaction Methods 0.000 claims description 2
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 claims description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
125000004417 unsaturated alkyl group Chemical group 0.000 claims description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims 4
BIXYYZIIJIXVFW-UUOKFMHZSA-N (2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BIXYYZIIJIXVFW-UUOKFMHZSA-N 0.000 claims 2
PGHYIISMDPKFKH-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(6-amino-2-bromopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Br)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O PGHYIISMDPKFKH-UUOKFMHZSA-N 0.000 claims 2
QCWBIPKYTBFWHH-FDDDBJFASA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-ethynylpyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C#C)=C1 QCWBIPKYTBFWHH-FDDDBJFASA-N 0.000 claims 2
NCZFDEBKMUJQQO-FDDDBJFASA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-ethynylpyrimidin-2-one Chemical compound C1=C(C#C)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NCZFDEBKMUJQQO-FDDDBJFASA-N 0.000 claims 2
208000023275 Autoimmune disease Diseases 0.000 claims 2
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical group CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 2
239000002126 C01EB10 - Adenosine Substances 0.000 claims 2
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 2
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims 2
229930010555 Inosine Natural products 0.000 claims 2
RRZQDHQSIKHKCN-PLDAJOQYSA-N O1[C@H](CO)C[C@@H](O)[C@@H]1N1C2=NC=NC(=N)C2(F)N=C1 Chemical compound O1[C@H](CO)C[C@@H](O)[C@@H]1N1C2=NC=NC(=N)C2(F)N=C1 RRZQDHQSIKHKCN-PLDAJOQYSA-N 0.000 claims 2
241000187747 Streptomyces Species 0.000 claims 2
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims 2
229960005305 adenosine Drugs 0.000 claims 2
239000003153 chemical reaction reagent Substances 0.000 claims 2
239000003086 colorant Substances 0.000 claims 2
229960003786 inosine Drugs 0.000 claims 2
239000000546 pharmaceutical excipient Substances 0.000 claims 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
QUNCBVFTYSPXAC-HCWSKCQFSA-N 1-[(2s,3r,4s,5r)-2-chloro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@@]1(Cl)N1C(=O)NC(=O)C=C1 QUNCBVFTYSPXAC-HCWSKCQFSA-N 0.000 claims 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
241001417495 Serranidae Species 0.000 claims 1
125000000304 alkynyl group Chemical group 0.000 claims 1
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims 1
125000001246 bromo group Chemical group Br* 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
210000002445 nipple Anatomy 0.000 claims 1
229940124531 pharmaceutical excipient Drugs 0.000 claims 1
102000004169 proteins and genes Human genes 0.000 claims 1
108090000623 proteins and genes Proteins 0.000 claims 1
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims 1
229940045145 uridine Drugs 0.000 claims 1
229940079593 drug Drugs 0.000 abstract description 5
AYWFLOPQIYDGTP-RJDJZVBFSA-N (2R,3S,4R,5R)-4-amino-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol 4-amino-1-[(2R,3R,4S,5R)-3-azido-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one (2R,3S,5R)-5-(6-amino-2-fluoropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol (2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-azido-2-(hydroxymethyl)oxolan-3-ol 5-fluoro-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound FC=1N=C(C=2N=CN([C@H]3C[C@H](O)[C@@H](CO)O3)C2N1)N.FC=1C(NC(N([C@H]2C[C@H](O)[C@@H](CO)O2)C1)=O)=O.N(=[N+]=[N-])[C@H]1[C@@H](O[C@@H]([C@H]1O)CO)N1C(=O)N=C(N)C=C1.N(=[N+]=[N-])[C@H]1[C@@H](O[C@@H]([C@H]1O)CO)N1C=NC=2C(N)=NC=NC12.N[C@H]1[C@@H](O[C@@H]([C@H]1O)CO)N1C=NC=2C(N)=NC=NC12 AYWFLOPQIYDGTP-RJDJZVBFSA-N 0.000 abstract 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
229910052717 sulfur Inorganic materials 0.000 abstract 1
239000011593 sulfur Substances 0.000 abstract 1
GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
229960001428 mercaptopurine Drugs 0.000 description 17
LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 14
229960002170 azathioprine Drugs 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
238000002474 experimental method Methods 0.000 description 11
NKGPJODWTZCHGF-UHFFFAOYSA-N 9-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound OC1C(O)C(CO)OC1N1C(NC=NC2=S)=C2N=C1 NKGPJODWTZCHGF-UHFFFAOYSA-N 0.000 description 10
206010051779 Bone marrow toxicity Diseases 0.000 description 9
231100000366 bone marrow toxicity Toxicity 0.000 description 9
239000003480 eluent Substances 0.000 description 9
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 8
159000000000 sodium salts Chemical class 0.000 description 8
238000003556 assay Methods 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
159000000007 calcium salts Chemical class 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
239000000243 solution Substances 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
210000002798 bone marrow cell Anatomy 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
239000000824 cytostatic agent Substances 0.000 description 5
125000003835 nucleoside group Chemical group 0.000 description 5
ORCOSNHPHKSKLF-UHFFFAOYSA-N 3-dodecylsulfanyldecan-2-yloxy propyl hydrogen phosphate Chemical compound CCCCCCCCCCCCSC(CCCCCCC)C(C)OOP(O)(=O)OCCC ORCOSNHPHKSKLF-UHFFFAOYSA-N 0.000 description 4
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
CPTIBDHUFVHUJK-NZYDNVMFSA-N mitopodozide Chemical compound C1([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H](CO)[C@@H]2C(=O)NNCC)=CC(OC)=C(OC)C(OC)=C1 CPTIBDHUFVHUJK-NZYDNVMFSA-N 0.000 description 1
229950010088 mitopodozide Drugs 0.000 description 1
230000011278 mitosis Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([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
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
238000011275 oncology therapy Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
125000002525 phosphocholine group Chemical class OP(=O)(OCC[N+](C)(C)C)O* 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
150000008223 ribosides Chemical class 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000007939 sustained release tablet Substances 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Immunology (AREA)
Bioinformatics & Cheminformatics (AREA)
Oncology (AREA)
Virology (AREA)
Communicable Diseases (AREA)
Hematology (AREA)
Transplantation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

FI964727A 1994-05-28 1996-11-27 Nukleosidimonofosfaattijohdannaiset, niiden valmistus ja käyttö immuunivastetta heikentävien lääkkeiden valmistukseen FI117673B (fi)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE4418690A DE4418690A1 (de)	1994-05-28	1994-05-28	Neue Lipidester von Nucleosid-Monophosphaten und deren Verwendung als immunsuppressive Arzneimittel
DE4418690		1994-05-28
EP9501951		1995-05-23
PCT/EP1995/001951 WO1995032984A1 (en)	1994-05-28	1995-05-23	New lipid esters of nucleoside monophosphates and their use as immunosuppressive drugs

Publications (3)

Publication Number	Publication Date
FI964727A0 FI964727A0 (fi)	1996-11-27
FI964727L FI964727L (fi)	1996-11-27
FI117673B true FI117673B (fi)	2007-01-15

Family

ID=6519215

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI964727A FI117673B (fi)	1994-05-28	1996-11-27	Nukleosidimonofosfaattijohdannaiset, niiden valmistus ja käyttö immuunivastetta heikentävien lääkkeiden valmistukseen

Country Status (27)

Country	Link
US (1)	US6025343A (zh)
EP (2)	EP0763049B1 (zh)
JP (1)	JP3802057B2 (zh)
KR (1)	KR100279087B1 (zh)
CN (1)	CN1168735C (zh)
AT (2)	ATE249472T1 (zh)
AU (1)	AU688516B2 (zh)
BR (1)	BR9507785A (zh)
CA (1)	CA2190983C (zh)
CZ (1)	CZ291846B6 (zh)
DE (3)	DE4418690A1 (zh)
DK (2)	DK0763049T3 (zh)
ES (2)	ES2199250T3 (zh)
FI (1)	FI117673B (zh)
HU (1)	HU220336B (zh)
IL (1)	IL113865A (zh)
MX (1)	MX9605809A (zh)
NO (1)	NO308998B1 (zh)
NZ (1)	NZ287434A (zh)
PL (1)	PL185290B1 (zh)
PT (2)	PT763049E (zh)
RU (1)	RU2165429C2 (zh)
SK (1)	SK284207B6 (zh)
TW (1)	TW420686B (zh)
UA (1)	UA45339C2 (zh)
WO (1)	WO1995032984A1 (zh)
ZA (1)	ZA954374B (zh)

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US5512671A (en) *	1993-02-16	1996-04-30	Wake Forest University	Ether lipid-nucleoside covalent conjugates

1994
- 1994-05-28 DE DE4418690A patent/DE4418690A1/de not_active Withdrawn
1995
- 1995-05-23 NZ NZ287434A patent/NZ287434A/en not_active IP Right Cessation
- 1995-05-23 DK DK95920864T patent/DK0763049T3/da active
- 1995-05-23 HU HU9603269A patent/HU220336B/hu not_active IP Right Cessation
- 1995-05-23 EP EP95920864A patent/EP0763049B1/en not_active Expired - Lifetime
- 1995-05-23 KR KR1019960706690A patent/KR100279087B1/ko not_active Expired - Fee Related
- 1995-05-23 DK DK02008360T patent/DK1229040T3/da active
- 1995-05-23 DE DE69530197T patent/DE69530197T2/de not_active Expired - Fee Related
- 1995-05-23 BR BR9507785A patent/BR9507785A/pt not_active Application Discontinuation
- 1995-05-23 RU RU96124383/04A patent/RU2165429C2/ru active
- 1995-05-23 PT PT95920864T patent/PT763049E/pt unknown
- 1995-05-23 AU AU26154/95A patent/AU688516B2/en not_active Ceased
- 1995-05-23 PT PT02008360T patent/PT1229040E/pt unknown
- 1995-05-23 MX MX9605809A patent/MX9605809A/es not_active IP Right Cessation
- 1995-05-23 CA CA002190983A patent/CA2190983C/en not_active Expired - Fee Related
- 1995-05-23 CZ CZ19963477A patent/CZ291846B6/cs not_active IP Right Cessation
- 1995-05-23 CN CNB951943715A patent/CN1168735C/zh not_active Expired - Fee Related
- 1995-05-23 SK SK1518-96A patent/SK284207B6/sk not_active IP Right Cessation
- 1995-05-23 JP JP50026296A patent/JP3802057B2/ja not_active Expired - Fee Related
- 1995-05-23 WO PCT/EP1995/001951 patent/WO1995032984A1/en not_active Ceased
- 1995-05-23 AT AT02008360T patent/ATE249472T1/de not_active IP Right Cessation
- 1995-05-23 EP EP02008360A patent/EP1229040B8/en not_active Expired - Lifetime
- 1995-05-23 AT AT95920864T patent/ATE236189T1/de not_active IP Right Cessation
- 1995-05-23 ES ES95920864T patent/ES2199250T3/es not_active Expired - Lifetime
- 1995-05-23 DE DE69531749T patent/DE69531749T2/de not_active Expired - Fee Related
- 1995-05-23 ES ES02008360T patent/ES2206429T3/es not_active Expired - Lifetime
- 1995-05-23 UA UA96114469A patent/UA45339C2/uk unknown
- 1995-05-24 TW TW084105233A patent/TW420686B/zh active
- 1995-05-25 IL IL113865A patent/IL113865A/en not_active IP Right Cessation
- 1995-05-29 ZA ZA954374A patent/ZA954374B/xx unknown
1996
- 1996-11-21 PL PL95317380A patent/PL185290B1/pl not_active IP Right Cessation
- 1996-11-27 NO NO965054A patent/NO308998B1/no not_active IP Right Cessation
- 1996-11-27 US US08/753,633 patent/US6025343A/en not_active Expired - Fee Related
- 1996-11-27 FI FI964727A patent/FI117673B/fi active IP Right Grant

Also Published As

Publication number	Publication date
CA2190983C (en)	2006-08-15
WO1995032984A8 (en)	2003-01-16
FI964727A0 (fi)	1996-11-27
PL185290B1 (pl)	2003-04-30
DE69531749T2 (de)	2004-07-29
EP1229040B8 (en)	2003-11-05
AU688516B2 (en)	1998-03-12
RU2165429C2 (ru)	2001-04-20
EP1229040A2 (en)	2002-08-07
IL113865A0 (en)	1995-08-31
EP1229040B1 (en)	2003-09-10
ZA954374B (en)	1996-11-29
SK284207B6 (en)	2004-11-03
CZ347796A3 (en)	1997-04-16
SK151896A3 (en)	1997-06-04
ATE249472T1 (de)	2003-09-15
AU2615495A (en)	1995-12-21
NO965054L (no)	1997-01-28
UA45339C2 (uk)	2002-04-15
HU9603269D0 (en)	1997-01-28
PL317380A1 (en)	1997-04-01
WO1995032984A1 (en)	1995-12-07
MX9605809A (es)	1997-12-31
CN1168735C (zh)	2004-09-29
KR100279087B1 (ko)	2001-01-15
CZ291846B6 (cs)	2003-06-18
PT763049E (pt)	2003-08-29
DE4418690A1 (de)	1996-01-11
US6025343A (en)	2000-02-15
NO308998B1 (no)	2000-11-27
HU220336B (hu)	2001-12-28
JP3802057B2 (ja)	2006-07-26
DE69530197D1 (de)	2003-05-08
DE69530197T2 (de)	2004-01-29
TW420686B (en)	2001-02-01
BR9507785A (pt)	1997-09-23
ES2199250T3 (es)	2004-02-16
DK0763049T3 (da)	2003-07-28
JPH10500964A (ja)	1998-01-27
DE69531749D1 (de)	2003-10-16
EP0763049B1 (en)	2003-04-02
CA2190983A1 (en)	1995-12-07
HUT75340A (en)	1997-05-28
PT1229040E (pt)	2003-12-31
NO965054D0 (no)	1996-11-27
NZ287434A (en)	1998-01-26
KR970703354A (ko)	1997-07-03
CN1154111A (zh)	1997-07-09
IL113865A (en)	2008-12-29
ATE236189T1 (de)	2003-04-15
DK1229040T3 (da)	2003-12-22
ES2206429T3 (es)	2004-05-16
EP0763049A1 (en)	1997-03-19
EP1229040A3 (en)	2002-08-21
FI964727L (fi)	1996-11-27

Publication	Publication Date	Title
FI117673B (fi)	2007-01-15	Nukleosidimonofosfaattijohdannaiset, niiden valmistus ja käyttö immuunivastetta heikentävien lääkkeiden valmistukseen
FI104176B (fi)	1999-11-30	Menetelmä nukleosidien uusien antiviraalisten forfolipidijohdannaisten valmistamiseksi
US5563257A (en)	1996-10-08	Phospholipid derivatives of nucleosides
DE19505168A1 (de)	1996-08-22	Spezifische Lipidkonjugate von Nucleosid-Diphosphonaten und deren Verwendung als Arzneimittel
DE602004001047T2 (de)	2007-04-19	Phospholipidester von Clofarabin
EP0155164B1 (en)	1988-11-17	Novel cyanoimidazole nucleoside derivatives
HU179949B (en)	1983-01-28	Process for preparing nitroso-carbamide derivatives
US4720497A (en)	1988-01-19	6-purinyl N-/2-chloroethyl/carbamate and thiocarbamate and process for the preparation thereof
US6080734A (en)	2000-06-27	Liponucleotides of seco-nucleosides, their production as well as their use as antiviral pharmaceutical agents
HU220611B1 (hu)	2002-03-28	Nukleozidok foszfolipidszármazékai, ezeket hatóanyagként tartalmazó gyógyszerkészítmények és az előállításukra szolgáló eljárások
FI90664B (fi)	1993-11-30	Menetelmä terapeuttisesti käyttökelpoisten 3'-atsido nukleosidien valmistamiseksi
JPS58222087A (ja)	1983-12-23	エリプチシン誘導体，その製造方法及び該化合物を含有する抗腫瘍治療剤

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1999-05-30	HC	Name/ company changed in application	Owner name: ROCHE DIAGNOSTICS GMBH
2007-01-15	FG	Patent granted	Ref document number: 117673 Country of ref document: FI

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