Title:
PRODRUGS OF PHOSPHONATE NUCLEOTIDE ANALOGUES AND METHODS FOR SELECTING AND MAKING SAME
Document Type and Number:
WIPO Patent Application WO2002008241
Kind Code:
A3
Abstract:
A novel method is provided for screening prodrugs of methoxyphosphonate nucleotide analogues to identify prodrugs selectively targeting desired tissues with antiviral or antitumor activity. This method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided. Also provided is an improved method for the use of magnesium alkoxide for the preparation of starting materials and compounds for use herein.
Inventors:
BECKER MARK W (US)
CHAPMAN HARLAN H (US)
CIHLAR TOMAS (US)
EISENBERG EUGENE J (US)
HE GONG-XIN (US)
KERNAN MICHAEL R (US)
LEE WILLIAM A (US)
PRISBE ERNEST J (US)
ROHLOFF JOHN C (US)
SPARACINO MARK L (US)
CHAPMAN HARLAN H (US)
CIHLAR TOMAS (US)
EISENBERG EUGENE J (US)
HE GONG-XIN (US)
KERNAN MICHAEL R (US)
LEE WILLIAM A (US)
PRISBE ERNEST J (US)
ROHLOFF JOHN C (US)
SPARACINO MARK L (US)
Application Number:
PCT/US2001/023104
Publication Date:
August 29, 2002
Filing Date:
July 20, 2001
Export Citation:
Assignee:
GILEAD SCIENCES INC (US)
BECKER MARK W (US)
CHAPMAN HARLAN H (US)
CIHLAR TOMAS (US)
EISENBERG EUGENE J (US)
HE GONG-XIN (US)
KERNAN MICHAEL R (US)
LEE WILLIAM A (US)
PRISBE ERNEST J (US)
ROHLOFF JOHN C (US)
SPARACINO MARK L (US)
BECKER MARK W (US)
CHAPMAN HARLAN H (US)
CIHLAR TOMAS (US)
EISENBERG EUGENE J (US)
HE GONG-XIN (US)
KERNAN MICHAEL R (US)
LEE WILLIAM A (US)
PRISBE ERNEST J (US)
ROHLOFF JOHN C (US)
SPARACINO MARK L (US)
International Classes:
A61K31/664; A61K31/675; A61P31/12; A61P31/18; A61P35/00; C07F9/6561; C07H19/10; C07H19/20; C07H21/00; C12Q1/18; G01N33/15; G01N33/50; G01N33/53; (IPC1-7): C07F9/6561; C07H19/20; G01N33/53; A61K31/675; A61P31/12; A61P35/00
Domestic Patent References:
| WO1996037503A1 | 1996-11-28 |
Foreign References:
| US5977089A | 1999-11-02 | |||
| EP0481214A1 | 1992-04-22 |
Other References:
SIDDIQUI A Q ET AL: "DESIGN AND SYNTHESIS OF LIPOPHILIC PHOSPHORAMIDATE D4T-MP PRODRUGS EXPRESSING HIGH POTENCY AGAINST HIV IN CELL CULTRURE: STRUCTURAL DETERMINANTS FOR IN VITRO ACTIVITY AND QSAR", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 42, no. 20, 1999, pages 4122 - 4128, XP000999173, ISSN: 0022-2623
H. CHAPMAN ET AL.: "Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340", NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS, vol. 20, 2001, pages 621 - 628, XP002202043
H. CHAPMAN ET AL.: "Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340", NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS, vol. 20, 2001, pages 621 - 628, XP002202043
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