Title:
METHODS AND COMPOSITIONS FOR TREATING FLAVIVIRUSES AND PESTIVIRUSES
Document Type and Number:
WIPO Patent Application WO2001092282
Kind Code:
A3
Abstract:
A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1', 2' or 3'-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.
Inventors:
SOMMADOSSI JEAN-PIERRE (US)
LACOLLA PAOLO (IT)
LACOLLA PAOLO (IT)
Application Number:
PCT/US2001/016687
Publication Date:
May 02, 2002
Filing Date:
May 23, 2001
Export Citation:
Assignee:
NOVIRIO PHARMACEUTICALS LTD (KY)
UNIV CAGLIARI (IT)
SOMMADOSSI JEAN PIERRE (US)
LACOLLA PAOLO (IT)
UNIV CAGLIARI (IT)
SOMMADOSSI JEAN PIERRE (US)
LACOLLA PAOLO (IT)
International Classes:
A61K31/7064; A61K31/7068; A61K31/7072; A61K31/7076; A61K31/708; C07H19/067; A61P1/04; A61P1/12; A61P25/00; A61P31/12; A61P31/14; A61P31/18; A61P43/00; C07H19/06; C07H19/10; C07H19/16; C07H19/167; C07H19/20; A61K; A61P; C07H; (IPC1-7): C07H19/06; C07H19/10; C07H19/16; C07H19/20; A61K31/7068; A61K31/7076; A61P31/14
Domestic Patent References:
| WO1999043691A1 | 1999-09-02 | |||
| WO2001090121A2 | 2001-11-29 |
Foreign References:
| US5977325A | 1999-11-02 | |||
| GB1209654A | 1970-10-21 | |||
| FR1521076A | 1968-04-12 | |||
| GB1163103A | 1969-09-04 | |||
| FR2662165A1 | 1991-11-22 | |||
| US5977061A | 1999-11-02 |
Other References:
X. MARTIN ET AL.: "Intramolecular hydrogen bonding in primary hydroxyl of thymine 1-(1-deoxy-beta-D-psicofuranosyl) nucleoside", TETRAHEDRON, vol. 50, 1994, pages 6689 - 6694, XP002176339
E. ROGERS ET AL.: "2'C-alkylribonucleosides: design, synthesis, and conformation", NUCLEOSIDES & NUCLEOTIDES, vol. 16, 1997, pages 1457 - 1460, XP002189347
J. FARKAS, F. SORM: "Nucleic acids components and their analogues. XCIV. Synthesis of 6-amino-9-(1-deoxy-beta-D-psicofuranosyl)purine", COLLECTION CZECHOSLOV. CHEM. COMM., vol. 32, 1967, pages 2663 - 2667, XP001016337
H. HREBABECKY, J. FARKAS: "Synthesis of 7- and 9-beta-D-psicofuranosylguanine and their 1'-deoxy derivatives", COLLECTION CZECHOSLOV. CHEM. COMM., vol. 39, 1974, pages 2115 - 2123, XP002176340
WOLFE M S ET AL: "A Concise Synthesis of 2'-C-Methylribonucleosides", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 36, no. 42, 16 October 1995 (1995-10-16), pages 7611 - 7614, XP004027097, ISSN: 0040-4039
P. FRANCHETTI ET AL.: "2'-C-Methyl analogues of selective adenosine receptor agonists: Synthesis and binding studies", J. MED. CHEM., vol. 41, 1998, pages 1708 - 1715, XP002189348
OIVANEN M ET AL: "ADDITIONAL EVIDENCE FOR THE EXCEPTIONAL MECHANISM OF THE ACID-CATALYSED HYDROLYSIS OF 4-OXOPYRIMIDINE NUCLEOSIDES: HYDROLYSIS OF 1-(1-ALKOXYALKYL)URACILS, SECONUCLEOSIDES, 3'-C-ALKYL NUCLEOSIDES AND NUCLEOSIDE 3',5'-CYCLIC MONOPHOSPHATES", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 2, CHEMICAL SOCIETY. LETCHWORTH, GB, vol. 2, 1994, pages 309 - 314, XP000886596, ISSN: 1472-779X
S.P. ONG ET AL.: "Synthesis of 3'-C-methyladenosine and 3'-C-methyluridine diphosphates and their interaction with the ribonucleoside diphosphate reductase from Corynebacterium nephridii", BIOCHEMISTRY, vol. 31, 1992, pages 11210 - 11215, XP002189349
L.N. BEIGELMAN ET AL.: "Epimerization during acetolysis of 3-O-acetyl-5-O-benzoyl-1,2-O-isopropylidene-3-C-methyl-alfa-D-ribofuranose.", CARBOHYDRATE RESEARCH, vol. 181, 1988, pages 77 - 88, XP002189350
H. HREBABECKY ET AL.: "Nucleic acid components and their analogues. CXLIX. Synthesis of pyrimidine nucleosides derived from 1-deoxy-D-psicose", COLLECTION CZECHOSLOV. CHEM. COMM., vol. 37, 1972, pages 2059 - 2065, XP002176338
A. GROUILLER ET AL.: "Novel p-toluenesulfonylation and thiocarbonylation of unprotected thymine nucleosides", SYNLETT, 1993, pages 221 - 222, XP002189351
S.N. MIKHAILOV ET AL.: "Hydrolysis of 2'- and 3'-c-methyluridine 2',3'-monophosphates and interconversion and dephosphorylation of the resulting 2'- and 3'-monophosphates: Comparison with the reactions of uridine monophosphates", J. ORG. CHEM., vol. 57, 1992, pages 4122 - 4126, XP002189352
MATSUDA A ET AL: "Nucleosides and nucleotides. 94. Radical deoxygenation of tert-alcohols in 1-(2-C-alkylpentafuranosyl)pyrimidines: Synthesis of (2'S)-2'-deoxy-2'-C-methylcytidine, an antileukemic nucleoside", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 34, 1991, pages 234 - 239, XP002178370, ISSN: 0022-2623
E. WALTON ET AL.: "Branched-chain sugar nucleosides. V. Synthesis and antiviral properties of several branched-chain sugar nucleosides", J. MED. CHEM., vol. 12, 1969, pages 306 - 309, XP002189353
V.L. TUNITSKAYA ET AL.: "Substrate properties of C'-methyl UTP derivatives in T7 RNA polymerase reactions. Evidence for N-type NTP conformation", FEBS LETTERS, vol. 400, 1997, pages 263 - 266, XP002189354
A. MATSUDA ET AL.: "Radical deoxygenation of tert-alcohols in 2'-branched-chain sugar pyrimidine nucleosides: synthesis and antileukemic activity of 2'-deoxy-2'(S)-methylcytidine", CHEM. PHARM. BULL., vol. 35, 1987, pages 3967 - 3970, XP002189355
A. MATSUDA ET AL.: "Alkyl addition reaction of pyrimidine 2'-ketonucleosides: synthesis of 2'-branched-chain sugar pyrimidine nucleosides", CHEM. PHARM. BULL., vol. 36, 1988, pages 945 - 953, XP002189356
ALTMANN ET AL: "The effects of 2'- and 3'-alkyl substituents on oligonucleotide hybridization and stability", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 4, no. 16, 1994, pages 1969 - 1974, XP002105090, ISSN: 0960-894X
L.N. BEIGELMAN ET AL.: "A general method for synthesis of 3'-alkylnucleosides", NUCLEIC ACIDS SYMP. SER., vol. 9, 1981, pages 115 - 118, XP001059721
S.N. MIKHAILOV ET AL.: "Synthesis and properties of 3'-C-methylnucleosides and their phosphoric esters", CARBOHYDRATE RESEARCH, vol. 124, 1983, pages 75 - 96, XP002189357
Y. ITOH ET AL.: "Divergent stereocontrolled approach to the synthesis of uracil nucleosides branched at the anomeric position", J. ORG. CHEM., vol. 60, 1995, pages 656 - 662, XP002189358
FAIVRE-BUET V ET AL: "SYNTHESIS OF 1'-DEOXYPSICOFURANOSYL-DEOXYNUCLEOSIDES AS POTENTIAL ANTI-HIV AGENTS", NUCLEOSIDES & NUCLEOTIDES, DEKKER, NEW YORK,NY,, US, vol. 11, no. 7, 1992, pages 1411 - 1424, XP001025527, ISSN: 0732-8311
SERAFINOWSKI P J ET AL: "NEW METHOD FOR THE PREPARATION OF SOME 2'- AND 3'-TRIFLUOROMETHYL- 2',3'-DIDEOXYURIDINE DERIVATIVES", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 56, no. 2, 1999, pages 333 - 339, XP001050335, ISSN: 0040-4020
HARAGUCHI K ET AL: "PREPARATION AND REACTIONS OF 2'- AND 3'-VINYL BROMIDES OF URACIL-NUCLEOSIDES: VERSATILE SYNTHONS FOR ANTI-HIV AGENTS", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 32, no. 28, 1991, pages 3391 - 3394, XP001041740, ISSN: 0040-4039
S.N. MIKHAILOV ET AL.: "Substrate properties of C'-methylnucleoside and C'-methyl-2'-deoxynucleoside 5'-triphosphates in RNA and DNA synthesis reactions catalysed by RNA and DNA polymerases", NUCLEOSIDES & NUCLEOTIDES, vol. 10, 1991, pages 339 - 343, XP001059775
AKIRA MATSUDA ET AL: "NUCLEOSIDES AND NUCLEOTIDES 104. RADICAL AND PALLADIUM-CATALYZED DEOXYGENATION OF THE ALLYLIC ALCOHOL SYSTEMS IN THE SUGAR MOIETY OF PYRIMIDINE NUCLEOSIDES", NUCLEOSIDES & NUCLEOTIDES, DEKKER, NEW YORK,NY,, US, vol. 11, no. 2/4, 1992, pages 197 - 226, XP000573757, ISSN: 0732-8311
T. IINO ET AL.: "Nucleosides and nucleotides. 139. Stereoselective synthesis of (2'S)-2'-C-alkyl-2'-deoxyuridines", NUCLEOSIDES & NUCLEOTIDES, vol. 15, 1996, pages 169 - 181, XP002189359
SHARMA P K ET AL: "SYNTHESIS OF 3'-TRIFLUOROMETHYL NUCLEOSIDES AS POTENTIAL ANTIVIRAL AGENTS", NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS, MARCEL DEKKER, ANN HARBOR, MI, US, vol. 19, no. 4, 2000, pages 757 - 774, XP001050475, ISSN: 1525-7770
J.-C. WU, J. CHATTOPADDYAYA: "A new stereospecific synthesis of [3.1.0] bicyclic cyclopropano analog of 2',3'-dideoxyuridine", TETRAHEDRON, vol. 46, 1990, pages 2587 - 2592, XP002189360
V. SAMANO, M.J. ROBBINS: "Synthesis and radical-induced ring-opening reactions of 2'-deoxyadenosine-2'-spirocyclopropane and its uridine analogue. Mechanistic probes for ribonucleotide reductases", J. AM. CHEM. SOC., vol. 114, 1992, pages 4007 - 4008, XP002189361
V. SAMANO, M.J. ROBINS: "Nucleic acid related compounds. 77.", CAN. J. CHEM., vol. 71, 1993, pages 186 - 191, XP002189362
C.R. JOHNSON, D.R. BHUMRALKAR: "3'-C-Trifluoromethyl ribonucleosides", NUCLEOSIDES & NUCLEOTIDES, vol. 14, 1995, pages 185 - 194, XP002189363
S. LAVAIRE ET AL.: "3'-Deoxy-3'-C-trifluoromethyl nucleosides: synthesis and antiviral evaluation", NUCLEOSIDES & NUCLEOTIDES, vol. 17, 1998, pages 2267 - 2280, XP002189364
TRITSCH D D ET AL: "3'-beta-ethynyl and 2'-deoxy-3'-beta-ethynyl adenosines: first 3'-beta-branched-adenosines substrates of adenosine deaminase", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 10, no. 2, January 2000 (2000-01-01), pages 139 - 141, XP004188802, ISSN: 0960-894X
I.I. FEDEROV ET AL.: "3'-C-Branched 2'-deoxy-5-methyluridines: Synthesis, enzyme inhibition, and antiviral properties", J. MED. CHEM., vol. 35, 1992, pages 4567 - 4575, XP002189365
S. CZERNECKI, A. EZZITOUNI: "Synthesis of various 3'-branched 2',3'-unsaturated pyrimidine nucleosides as potential anti-HIV agents", J. ORG. CHEM., vol. 57, 1992, pages 7325 - 7328, XP002189366
H. HATTORI ET AL.: "Nucleosides and nucleotides. 175.", J. MED. CHEM., vol. 41, 1998, pages 2892 - 2902, XP002189367
A. ROSENTHAL, S.N. MIKHAILOV: "Branched-chain sugar nucleosides. Synthesis of 3'-C-ethyl (and 3'-C-butyl)uridine", CARBOHYDRATE RESEARCH, vol. 79, 1980, pages 235 - 242, XP002189368
K. HARAGUCHI ET AL.: "Stereoselective synthesis of 1'-C-branched uracil nucleosides from uridine", NUCLEOSIDES & NUCLEOTIDES, vol. 14, 1995, pages 417 - 420, XP002189369
ALTMANN ET AL: "The synthesis of 1'-methyl carbocyclic thymidine and its effect on nucleic acid duplex stability", SYNLETT, THIEME VERLAG, STUTTGART, DE, no. 10, October 1994 (1994-10-01), pages 853 - 855, XP002105092, ISSN: 0936-5214
M. KAWANA ET AL.: "The deoxygenations of tosylated adenosine derivatives with Grignard reagents", NUCLEIC ACIDS SYMP. SER., vol. 17, 1986, pages 37 - 40, XP001059719
K. WALCZAK, E.B. PEDERSEN: "Synthesis of 1-(3-alkyl-2,3-dideoxy-D-pentofuranosyl)uracils with potential anti-HIV activity", ACTA CHEM. SCAND., vol. 45, 1991, pages 930 - 934, XP002189370
H. USUI, T. UEDA: "Synthesis of 2'-deoxy-8,2'-ethanoadenosine and 3'-deoxy-8,3'-ethanoadenosine (Nucleosides and nucleotides. LXIV)", CHEM. PHARM. BULL., vol. 34, 1986, pages 15 - 23, XP002189371
LEYSSEN P ET AL: "PERSPECTIVES FOR THE TREATMENT OF INFECTIONS WITH FLAVIVIRIDAE", CLINICAL MICROBIOLOGY REVIEWS, WASHINGTON, DC, US, vol. 13, no. 1, January 2000 (2000-01-01), pages 67 - 82, XP000889854, ISSN: 0893-8512
E. ROGERS ET AL.: "2'C-alkylribonucleosides: design, synthesis, and conformation", NUCLEOSIDES & NUCLEOTIDES, vol. 16, 1997, pages 1457 - 1460, XP002189347
J. FARKAS, F. SORM: "Nucleic acids components and their analogues. XCIV. Synthesis of 6-amino-9-(1-deoxy-beta-D-psicofuranosyl)purine", COLLECTION CZECHOSLOV. CHEM. COMM., vol. 32, 1967, pages 2663 - 2667, XP001016337
H. HREBABECKY, J. FARKAS: "Synthesis of 7- and 9-beta-D-psicofuranosylguanine and their 1'-deoxy derivatives", COLLECTION CZECHOSLOV. CHEM. COMM., vol. 39, 1974, pages 2115 - 2123, XP002176340
WOLFE M S ET AL: "A Concise Synthesis of 2'-C-Methylribonucleosides", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 36, no. 42, 16 October 1995 (1995-10-16), pages 7611 - 7614, XP004027097, ISSN: 0040-4039
P. FRANCHETTI ET AL.: "2'-C-Methyl analogues of selective adenosine receptor agonists: Synthesis and binding studies", J. MED. CHEM., vol. 41, 1998, pages 1708 - 1715, XP002189348
OIVANEN M ET AL: "ADDITIONAL EVIDENCE FOR THE EXCEPTIONAL MECHANISM OF THE ACID-CATALYSED HYDROLYSIS OF 4-OXOPYRIMIDINE NUCLEOSIDES: HYDROLYSIS OF 1-(1-ALKOXYALKYL)URACILS, SECONUCLEOSIDES, 3'-C-ALKYL NUCLEOSIDES AND NUCLEOSIDE 3',5'-CYCLIC MONOPHOSPHATES", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 2, CHEMICAL SOCIETY. LETCHWORTH, GB, vol. 2, 1994, pages 309 - 314, XP000886596, ISSN: 1472-779X
S.P. ONG ET AL.: "Synthesis of 3'-C-methyladenosine and 3'-C-methyluridine diphosphates and their interaction with the ribonucleoside diphosphate reductase from Corynebacterium nephridii", BIOCHEMISTRY, vol. 31, 1992, pages 11210 - 11215, XP002189349
L.N. BEIGELMAN ET AL.: "Epimerization during acetolysis of 3-O-acetyl-5-O-benzoyl-1,2-O-isopropylidene-3-C-methyl-alfa-D-ribofuranose.", CARBOHYDRATE RESEARCH, vol. 181, 1988, pages 77 - 88, XP002189350
H. HREBABECKY ET AL.: "Nucleic acid components and their analogues. CXLIX. Synthesis of pyrimidine nucleosides derived from 1-deoxy-D-psicose", COLLECTION CZECHOSLOV. CHEM. COMM., vol. 37, 1972, pages 2059 - 2065, XP002176338
A. GROUILLER ET AL.: "Novel p-toluenesulfonylation and thiocarbonylation of unprotected thymine nucleosides", SYNLETT, 1993, pages 221 - 222, XP002189351
S.N. MIKHAILOV ET AL.: "Hydrolysis of 2'- and 3'-c-methyluridine 2',3'-monophosphates and interconversion and dephosphorylation of the resulting 2'- and 3'-monophosphates: Comparison with the reactions of uridine monophosphates", J. ORG. CHEM., vol. 57, 1992, pages 4122 - 4126, XP002189352
MATSUDA A ET AL: "Nucleosides and nucleotides. 94. Radical deoxygenation of tert-alcohols in 1-(2-C-alkylpentafuranosyl)pyrimidines: Synthesis of (2'S)-2'-deoxy-2'-C-methylcytidine, an antileukemic nucleoside", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 34, 1991, pages 234 - 239, XP002178370, ISSN: 0022-2623
E. WALTON ET AL.: "Branched-chain sugar nucleosides. V. Synthesis and antiviral properties of several branched-chain sugar nucleosides", J. MED. CHEM., vol. 12, 1969, pages 306 - 309, XP002189353
V.L. TUNITSKAYA ET AL.: "Substrate properties of C'-methyl UTP derivatives in T7 RNA polymerase reactions. Evidence for N-type NTP conformation", FEBS LETTERS, vol. 400, 1997, pages 263 - 266, XP002189354
A. MATSUDA ET AL.: "Radical deoxygenation of tert-alcohols in 2'-branched-chain sugar pyrimidine nucleosides: synthesis and antileukemic activity of 2'-deoxy-2'(S)-methylcytidine", CHEM. PHARM. BULL., vol. 35, 1987, pages 3967 - 3970, XP002189355
A. MATSUDA ET AL.: "Alkyl addition reaction of pyrimidine 2'-ketonucleosides: synthesis of 2'-branched-chain sugar pyrimidine nucleosides", CHEM. PHARM. BULL., vol. 36, 1988, pages 945 - 953, XP002189356
ALTMANN ET AL: "The effects of 2'- and 3'-alkyl substituents on oligonucleotide hybridization and stability", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 4, no. 16, 1994, pages 1969 - 1974, XP002105090, ISSN: 0960-894X
L.N. BEIGELMAN ET AL.: "A general method for synthesis of 3'-alkylnucleosides", NUCLEIC ACIDS SYMP. SER., vol. 9, 1981, pages 115 - 118, XP001059721
S.N. MIKHAILOV ET AL.: "Synthesis and properties of 3'-C-methylnucleosides and their phosphoric esters", CARBOHYDRATE RESEARCH, vol. 124, 1983, pages 75 - 96, XP002189357
Y. ITOH ET AL.: "Divergent stereocontrolled approach to the synthesis of uracil nucleosides branched at the anomeric position", J. ORG. CHEM., vol. 60, 1995, pages 656 - 662, XP002189358
FAIVRE-BUET V ET AL: "SYNTHESIS OF 1'-DEOXYPSICOFURANOSYL-DEOXYNUCLEOSIDES AS POTENTIAL ANTI-HIV AGENTS", NUCLEOSIDES & NUCLEOTIDES, DEKKER, NEW YORK,NY,, US, vol. 11, no. 7, 1992, pages 1411 - 1424, XP001025527, ISSN: 0732-8311
SERAFINOWSKI P J ET AL: "NEW METHOD FOR THE PREPARATION OF SOME 2'- AND 3'-TRIFLUOROMETHYL- 2',3'-DIDEOXYURIDINE DERIVATIVES", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 56, no. 2, 1999, pages 333 - 339, XP001050335, ISSN: 0040-4020
HARAGUCHI K ET AL: "PREPARATION AND REACTIONS OF 2'- AND 3'-VINYL BROMIDES OF URACIL-NUCLEOSIDES: VERSATILE SYNTHONS FOR ANTI-HIV AGENTS", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 32, no. 28, 1991, pages 3391 - 3394, XP001041740, ISSN: 0040-4039
S.N. MIKHAILOV ET AL.: "Substrate properties of C'-methylnucleoside and C'-methyl-2'-deoxynucleoside 5'-triphosphates in RNA and DNA synthesis reactions catalysed by RNA and DNA polymerases", NUCLEOSIDES & NUCLEOTIDES, vol. 10, 1991, pages 339 - 343, XP001059775
AKIRA MATSUDA ET AL: "NUCLEOSIDES AND NUCLEOTIDES 104. RADICAL AND PALLADIUM-CATALYZED DEOXYGENATION OF THE ALLYLIC ALCOHOL SYSTEMS IN THE SUGAR MOIETY OF PYRIMIDINE NUCLEOSIDES", NUCLEOSIDES & NUCLEOTIDES, DEKKER, NEW YORK,NY,, US, vol. 11, no. 2/4, 1992, pages 197 - 226, XP000573757, ISSN: 0732-8311
T. IINO ET AL.: "Nucleosides and nucleotides. 139. Stereoselective synthesis of (2'S)-2'-C-alkyl-2'-deoxyuridines", NUCLEOSIDES & NUCLEOTIDES, vol. 15, 1996, pages 169 - 181, XP002189359
SHARMA P K ET AL: "SYNTHESIS OF 3'-TRIFLUOROMETHYL NUCLEOSIDES AS POTENTIAL ANTIVIRAL AGENTS", NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS, MARCEL DEKKER, ANN HARBOR, MI, US, vol. 19, no. 4, 2000, pages 757 - 774, XP001050475, ISSN: 1525-7770
J.-C. WU, J. CHATTOPADDYAYA: "A new stereospecific synthesis of [3.1.0] bicyclic cyclopropano analog of 2',3'-dideoxyuridine", TETRAHEDRON, vol. 46, 1990, pages 2587 - 2592, XP002189360
V. SAMANO, M.J. ROBBINS: "Synthesis and radical-induced ring-opening reactions of 2'-deoxyadenosine-2'-spirocyclopropane and its uridine analogue. Mechanistic probes for ribonucleotide reductases", J. AM. CHEM. SOC., vol. 114, 1992, pages 4007 - 4008, XP002189361
V. SAMANO, M.J. ROBINS: "Nucleic acid related compounds. 77.", CAN. J. CHEM., vol. 71, 1993, pages 186 - 191, XP002189362
C.R. JOHNSON, D.R. BHUMRALKAR: "3'-C-Trifluoromethyl ribonucleosides", NUCLEOSIDES & NUCLEOTIDES, vol. 14, 1995, pages 185 - 194, XP002189363
S. LAVAIRE ET AL.: "3'-Deoxy-3'-C-trifluoromethyl nucleosides: synthesis and antiviral evaluation", NUCLEOSIDES & NUCLEOTIDES, vol. 17, 1998, pages 2267 - 2280, XP002189364
TRITSCH D D ET AL: "3'-beta-ethynyl and 2'-deoxy-3'-beta-ethynyl adenosines: first 3'-beta-branched-adenosines substrates of adenosine deaminase", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 10, no. 2, January 2000 (2000-01-01), pages 139 - 141, XP004188802, ISSN: 0960-894X
I.I. FEDEROV ET AL.: "3'-C-Branched 2'-deoxy-5-methyluridines: Synthesis, enzyme inhibition, and antiviral properties", J. MED. CHEM., vol. 35, 1992, pages 4567 - 4575, XP002189365
S. CZERNECKI, A. EZZITOUNI: "Synthesis of various 3'-branched 2',3'-unsaturated pyrimidine nucleosides as potential anti-HIV agents", J. ORG. CHEM., vol. 57, 1992, pages 7325 - 7328, XP002189366
H. HATTORI ET AL.: "Nucleosides and nucleotides. 175.", J. MED. CHEM., vol. 41, 1998, pages 2892 - 2902, XP002189367
A. ROSENTHAL, S.N. MIKHAILOV: "Branched-chain sugar nucleosides. Synthesis of 3'-C-ethyl (and 3'-C-butyl)uridine", CARBOHYDRATE RESEARCH, vol. 79, 1980, pages 235 - 242, XP002189368
K. HARAGUCHI ET AL.: "Stereoselective synthesis of 1'-C-branched uracil nucleosides from uridine", NUCLEOSIDES & NUCLEOTIDES, vol. 14, 1995, pages 417 - 420, XP002189369
ALTMANN ET AL: "The synthesis of 1'-methyl carbocyclic thymidine and its effect on nucleic acid duplex stability", SYNLETT, THIEME VERLAG, STUTTGART, DE, no. 10, October 1994 (1994-10-01), pages 853 - 855, XP002105092, ISSN: 0936-5214
M. KAWANA ET AL.: "The deoxygenations of tosylated adenosine derivatives with Grignard reagents", NUCLEIC ACIDS SYMP. SER., vol. 17, 1986, pages 37 - 40, XP001059719
K. WALCZAK, E.B. PEDERSEN: "Synthesis of 1-(3-alkyl-2,3-dideoxy-D-pentofuranosyl)uracils with potential anti-HIV activity", ACTA CHEM. SCAND., vol. 45, 1991, pages 930 - 934, XP002189370
H. USUI, T. UEDA: "Synthesis of 2'-deoxy-8,2'-ethanoadenosine and 3'-deoxy-8,3'-ethanoadenosine (Nucleosides and nucleotides. LXIV)", CHEM. PHARM. BULL., vol. 34, 1986, pages 15 - 23, XP002189371
LEYSSEN P ET AL: "PERSPECTIVES FOR THE TREATMENT OF INFECTIONS WITH FLAVIVIRIDAE", CLINICAL MICROBIOLOGY REVIEWS, WASHINGTON, DC, US, vol. 13, no. 1, January 2000 (2000-01-01), pages 67 - 82, XP000889854, ISSN: 0893-8512
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