IL106840A - Process for basic anatomization of pentopornosyl nucleosides - Google Patents

Process for basic anatomization of pentopornosyl nucleosides

Info

Publication number: IL106840A
Authority: IL; Israel
Prior art keywords: hydroxide; lower alkyl; fluoro; hydroxy; group
Prior art date: 1992-09-01

Application number

IL10684093A

Other languages

English (en)

Hebrew (he)

Other versions

IL106840A0 (en

Original Assignee

Lilly Co Eli

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.)

1992-09-01

Filing date

1993-08-30

Publication date

1998-09-24

1993-08-30 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1993-12-08 Publication of IL106840A0 publication Critical patent/IL106840A0/xx

1998-09-24 Publication of IL106840A publication Critical patent/IL106840A/en

Links

238000000034 method Methods 0.000 title claims abstract description 55
239000002777 nucleoside Substances 0.000 title claims abstract description 53
125000003835 nucleoside group Chemical group 0.000 title abstract description 16
150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 32
239000000203 mixture Substances 0.000 claims abstract description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims abstract description 16
239000003960 organic solvent Substances 0.000 claims abstract description 5
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 84
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 60
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
239000002585 base Substances 0.000 claims description 23
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000000217 alkyl group Chemical group 0.000 claims description 20
125000001153 fluoro group Chemical group F* 0.000 claims description 19
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 14
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
239000002904 solvent Substances 0.000 claims description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
-1 azido, hydroxy Chemical group 0.000 claims description 7
125000006239 protecting group Chemical group 0.000 claims description 7
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 5
ABSOMGPQFXJESQ-UHFFFAOYSA-M cesium;hydroxide;hydrate Chemical compound O.[OH-].[Cs+] ABSOMGPQFXJESQ-UHFFFAOYSA-M 0.000 claims description 5
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 3
229910001863 barium hydroxide Inorganic materials 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 2
125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
235000011114 ammonium hydroxide Nutrition 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
235000011118 potassium hydroxide Nutrition 0.000 description 18
229940093932 potassium hydroxide Drugs 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
238000004128 high performance liquid chromatography Methods 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
229910052757 nitrogen Inorganic materials 0.000 description 10
238000010992 reflux Methods 0.000 description 10
239000000243 solution Substances 0.000 description 10
125000004435 hydrogen atom Chemical class [H]* 0.000 description 7
239000002253 acid Substances 0.000 description 4
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
238000000926 separation method Methods 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000002773 nucleotide Substances 0.000 description 3
125000003729 nucleotide group Chemical group 0.000 description 3
239000008363 phosphate buffer Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 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 description 2
125000003118 aryl group Chemical group 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
150000007523 nucleic acids Chemical class 0.000 description 2
102000039446 nucleic acids Human genes 0.000 description 2
108020004707 nucleic acids Proteins 0.000 description 2
238000011084 recovery Methods 0.000 description 2
WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
229940045145 uridine Drugs 0.000 description 2
VLGYFAFWTFUVSB-YXZULKJRSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-sulfanylpyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1S VLGYFAFWTFUVSB-YXZULKJRSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
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 description 1
QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
101000911753 Homo sapiens Protein FAM107B Proteins 0.000 description 1
101000760832 Homo sapiens tRNA wybutosine-synthesizing protein 2 homolog Proteins 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
102100026983 Protein FAM107B Human genes 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
238000007605 air drying Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 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 description 1
230000004071 biological effect Effects 0.000 description 1
238000012925 biological evaluation Methods 0.000 description 1
BFAKENXZKHGIGE-UHFFFAOYSA-N bis(2,3,5,6-tetrafluoro-4-iodophenyl)diazene Chemical compound FC1=C(C(=C(C(=C1F)I)F)F)N=NC1=C(C(=C(C(=C1F)F)I)F)F BFAKENXZKHGIGE-UHFFFAOYSA-N 0.000 description 1
SIOVKLKJSOKLIF-UHFFFAOYSA-N bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)OC(C)=N[Si](C)(C)C SIOVKLKJSOKLIF-UHFFFAOYSA-N 0.000 description 1
244000309464 bull Species 0.000 description 1
229910052792 caesium Inorganic materials 0.000 description 1
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
229940104302 cytosine Drugs 0.000 description 1
230000007423 decrease Effects 0.000 description 1
239000005549 deoxyribonucleoside Substances 0.000 description 1
238000007865 diluting Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
125000003843 furanosyl group Chemical group 0.000 description 1
125000001183 hydrocarbyl group Chemical group 0.000 description 1
JEGUKCSWCFPDGT-UHFFFAOYSA-M hydroxide;hydrate Chemical compound O.[OH-] JEGUKCSWCFPDGT-UHFFFAOYSA-M 0.000 description 1
239000012535 impurity Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002718 pyrimidine nucleoside Substances 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
102100024563 tRNA wybutosine-synthesizing protein 2 homolog Human genes 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
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 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
229940035893 uracil Drugs 0.000 description 1
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 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
- 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
- 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
- C07H19/048—Pyridine radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

IL10684093A 1992-09-01 1993-08-30 Process for basic anatomization of pentopornosyl nucleosides IL106840A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US93879192A	1992-09-01	1992-09-01

Publications (2)

Publication Number	Publication Date
IL106840A0 IL106840A0 (en)	1993-12-08
IL106840A true IL106840A (en)	1998-09-24

Family

ID=25471966

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10684093A IL106840A (en)	1992-09-01	1993-08-30	Process for basic anatomization of pentopornosyl nucleosides

Country Status (15)

Country	Link
US (1)	US5420266A (de)
EP (1)	EP0587364B1 (de)
JP (1)	JP3462893B2 (de)
KR (1)	KR100252451B1 (de)
AT (1)	ATE138929T1 (de)
BR (1)	BR9303658A (de)
CA (1)	CA2105112C (de)
DE (1)	DE69302977T2 (de)
DK (1)	DK0587364T3 (de)
ES (1)	ES2090880T3 (de)
GR (1)	GR3020426T3 (de)
HU (1)	HU214980B (de)
IL (1)	IL106840A (de)
MX (1)	MX9305301A (de)
TW (1)	TW356472B (de)

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US5637688A (en) *	1994-12-13	1997-06-10	Eli Lilly And Company	Process for preparing 1-(2'-deoxy-2'-difluoro-d-ribofuranosyl)-4-aminopyrimidin-2-one hydrochloride
US5869461A (en) *	1995-03-16	1999-02-09	Yale University	Reducing toxicity of L-nucleosides with D-nucleosides
US5633367A (en) *	1995-03-24	1997-05-27	Eli Lilly And Company	Process for the preparation of a 2-substituted 3,3-difluorofuran
CA2171518A1 (en) *	1995-03-24	1996-09-25	Douglas Patton Kjell	Process for the preparation of 2,2'-anhydro- and 2' -keto-1-(3', 5'-di-o-protected-.beta.-d-arabinofuranosyl) nucleosides
US6013790A (en) *	1996-09-25	2000-01-11	Board Of Regents University Of Nebraska-Lincoln	Heavily fluorinated sugar analogs
US6248878B1 (en) *	1996-12-24	2001-06-19	Ribozyme Pharmaceuticals, Inc.	Nucleoside analogs
MY164523A (en)	2000-05-23	2017-12-29	Univ Degli Studi Cagliari	Methods and compositions for treating hepatitis c virus
PL359169A1 (en)	2000-05-26	2004-08-23	Idenix (Cayman) Limited	Methods and compositions for treating flaviviruses and pestiviruses
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CN101172993A (zh)	2002-06-28	2008-05-07	埃迪尼克斯(开曼)有限公司	用于治疗黄病毒感染的2′－c－甲基－3′－o－l－缬氨酸酯核糖呋喃基胞苷
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KR20050035194A (ko)	2002-06-28	2005-04-15	이데닉스 (케이만) 리미티드	플라비비리다에 감염 치료용 2'-ｃ-메틸-3'-ｏ-ｌ-발린에스테르 리보푸라노실 사이티딘
AU2003298658A1 (en)	2002-11-15	2004-06-15	Idenix (Cayman) Limited	2'-branched nucleosides and flaviviridae mutation
US7598373B2 (en)	2002-12-12	2009-10-06	Idenix Pharmaceuticals, Inc.	Process for the production of 2-C-methyl-D-ribonolactone
RU2358979C2 (ru) *	2003-05-30	2009-06-20	Фармассет, Инк.	Модифицированные фторированные аналоги нуклеозида
CN101023094B (zh) *	2004-07-21	2011-05-18	法莫赛特股份有限公司	烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备
ES2725457T3 (es)	2004-09-14	2019-09-24	Gilead Pharmasset Llc	Preparación de ribofuranosil pirimidinas y purinas 2'fluoro-2'-alquil-sustituidas u otras opcionalmente sustituidas y sus derivados
DE602005019626D1 (de) *	2005-03-04	2010-04-08	Fresenius Kabi Oncology Ltd	Zwischenprodukt und verfahren zur herstellung von an beta-anomeren angereicherten 2'-desoxy,2',2'-difluor-d-ribufuranosylnukleosiden
US7781576B2 (en)	2005-12-23	2010-08-24	Idenix Pharmaceuticals, Inc.	Process for preparing a synthetic intermediate for preparation of branched nucleosides
US7964580B2 (en) *	2007-03-30	2011-06-21	Pharmasset, Inc.	Nucleoside phosphoramidate prodrugs
US8173621B2 (en) *	2008-06-11	2012-05-08	Gilead Pharmasset Llc	Nucleoside cyclicphosphates
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AR074897A1 (es) *	2008-12-23	2011-02-23	Pharmasset Inc	Fosforamidatos de nucleosidos
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US8618076B2 (en)	2009-05-20	2013-12-31	Gilead Pharmasset Llc	Nucleoside phosphoramidates
TWI576352B (zh)	2009-05-20	2017-04-01	基利法瑪席特有限責任公司	核苷磷醯胺
AP2012006535A0 (en)	2010-03-31	2012-10-31	Gilead Pharmasset Llc	Stereoselective synthesis of phosphorous containing actives
PL3290428T3 (pl)	2010-03-31	2022-02-07	Gilead Pharmasset Llc	Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu
ES2716158T3 (es)	2010-11-30	2019-06-10	Gilead Pharmasset Llc	2'-spiro-nucleótidos para el tratamiento de hepatitis C
US8889159B2 (en)	2011-11-29	2014-11-18	Gilead Pharmasset Llc	Compositions and methods for treating hepatitis C virus
CN102603838B (zh) *	2012-02-14	2015-02-18	江苏八巨药业有限公司	一种制备吉西他滨盐酸盐的方法
EA201690473A1 (ru)	2013-08-27	2017-03-31	ГАЙЛИД ФАРМАССЕТ ЭлЭлСи	Комбинированный состав двух противовирусных соединений
AU2019296174B2 (en)	2018-06-29	2021-10-07	Changchun Changcheng Pharmaceutical Technology Co., LTD	Phosphorus-containing prodrugs of gemcitabine
CN121949418B (zh) *	2026-04-01	2026-07-28	山东安弘制药有限公司	一种盐酸吉西他滨的制备方法

1993
- 1993-08-30 CA CA002105112A patent/CA2105112C/en not_active Expired - Lifetime
- 1993-08-30 KR KR1019930017031A patent/KR100252451B1/ko not_active Expired - Fee Related
- 1993-08-30 IL IL10684093A patent/IL106840A/en not_active IP Right Cessation
- 1993-08-30 TW TW082107028A patent/TW356472B/zh active
- 1993-08-30 HU HU9302452A patent/HU214980B/hu not_active IP Right Cessation
- 1993-08-31 DE DE69302977T patent/DE69302977T2/de not_active Expired - Lifetime
- 1993-08-31 MX MX9305301A patent/MX9305301A/es unknown
- 1993-08-31 DK DK93306886.8T patent/DK0587364T3/da active
- 1993-08-31 JP JP21565393A patent/JP3462893B2/ja not_active Expired - Fee Related
- 1993-08-31 AT AT93306886T patent/ATE138929T1/de not_active IP Right Cessation
- 1993-08-31 BR BR9303658A patent/BR9303658A/pt not_active Application Discontinuation
- 1993-08-31 EP EP93306886A patent/EP0587364B1/de not_active Expired - Lifetime
- 1993-08-31 ES ES93306886T patent/ES2090880T3/es not_active Expired - Lifetime
1994
- 1994-01-03 US US08/176,981 patent/US5420266A/en not_active Expired - Lifetime
1996
- 1996-07-02 GR GR960401799T patent/GR3020426T3/el unknown

Also Published As

Publication number	Publication date
DE69302977T2 (de)	1996-10-31
JP3462893B2 (ja)	2003-11-05
US5420266A (en)	1995-05-30
ATE138929T1 (de)	1996-06-15
ES2090880T3 (es)	1996-10-16
KR100252451B1 (ko)	2000-04-15
DK0587364T3 (da)	1996-07-01
GR3020426T3 (en)	1996-10-31
TW356472B (en)	1999-04-21
CA2105112C (en)	2005-08-02
IL106840A0 (en)	1993-12-08
JPH06157571A (ja)	1994-06-03
KR940007053A (ko)	1994-04-26
MX9305301A (es)	1994-06-30
HU9302452D0 (en)	1993-11-29
CA2105112A1 (en)	1994-03-02
BR9303658A (pt)	1994-03-22
HU214980B (hu)	1998-08-28
HUT65137A (en)	1994-04-28
DE69302977D1 (de)	1996-07-11
EP0587364B1 (de)	1996-06-05
EP0587364A1 (de)	1994-03-16

Legal Events

Date	Code	Title
1999-01-26	FF	Patent granted
1999-07-14	KB	Patent renewed
1999-12-31	KB	Patent renewed
2001-06-14	RH	Patent void
2004-05-12	RH1	Patent not in force

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US5401838A (en)	1995-03-28	Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides
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CA2098881C (en)	2005-06-07	Stereoselective glycosylation process
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US8168766B2 (en)	2012-05-01	Process of making 2-deoxy-2,2-difluoro-D-ribofuranosyl nucleosides and intermediates therefor
Katz et al.	1983	Synthesis and transformation of certain pyridazine cyclonucleosides
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