(12) Ulllted States Patent
`So?a et a].
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`US 7,964,580 B2
`Jun. 21, 2011
`
`US007964580B2
`
`(54) NUCLEOSIDE PHOSPHORAMIDATE
`PRODRUGS
`_
`(75) Inventors: Michael Joseph So?a, DoylestoWn, PA
`(US); Jinfa Du, New Hope, PA (US);
`-
`Pelyuan Wang, Glen Rock, N] (US)
`(73) Assignee: Pharmasset, Inc., Princeton, NJ (US)
`
`a
`
`a
`
`ou
`
`gillwin
`2
`5,372,808 A 12/1994 Blatt
`5,376,380 A 12/1994 Kikuchi
`5,405,598 A
`4/1995 Schinazi
`5,411,947 A
`5/1995 Hostetler
`5,420,266 A
`5/1995 Britton
`5,426,183 A
`@1995 Kjell
`5’453’499 A
`9/1995 ,Chou
`(Continued)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 370 days.
`
`CN
`
`(21) App1.No.: 12/053,015
`
`FOREIGN PATENT DOCUMENTS
`101108870
`1/2008
`(Continued)
`OTHER PUBLICATIONS
`
`(22) Flled:
`
`Mar- 21’ 2008
`
`Abraham et al. J. Med. Chem. (1996), vol. 39, pp. 4569-4575.*
`
`(65)
`
`Prior Publication Data
`
`Us 2010/0016251A1
`(51) Int- Cl‘
`
`Jan- 21, 2010
`
`(Continued)
`
`Primary Examiner * Patrick T LeWis
`(74) Attorney, Agent, or Firm * Merchant & Gould, PC
`
`(2006.01)
`A01N 43/04
`(200601)
`A61K31/70
`(52) U-s- Cl- -------------- ~~ 514/51; 514/43; 514/ 49; 514/50;
`536/25-3; 536/281; 536/284
`(58) Field of Classi?cation Search ...................... .. None
`See application ?le fOr complete Search history-
`
`ABSTRACT
`(57)
`Disclosed herein are phosphoramidate prodrugs of nucleo
`side derivatives for the treatment of viral infections in mam
`mals, Which is a compound, its stereoisomer, salt (acid or
`basic addition salt), hydrate, solvate, or crystalline form
`thereof, represented by the following structure:
`
`(56)
`
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`~_.
`s
`Y
`
`.z
`a
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`
`Also disclosed are methods of treatment, uses, and processes
`for preparing each of Which utiliZe the compound represented
`by formula I.
`
`14 Claims, No Drawings
`
`IPR2018-00119
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`I-MAK 1001
`
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`577927834 A
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`578307905 A 11/1998 D1219".
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`27883723? 2
`28888 gclhmazl
`u‘? .
`7
`7
`579227757 A
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`278237832 2 188888 gprllclfe
`°
`7
`7
`670437077 A
`3/2000 Barber
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`7
`7
`.
`671807134 B1
`V2001 ZahPSkY.
`672327300 B1
`5/2001 SChmaZ‘
`672397159 B1
`5/2001 Brown .
`673487587 B1
`2/2002 SChmaZl
`673727883 B1
`‘V2002 AHWOOC.‘
`673917859 B1
`5/2002 5911mm
`674107531 B1
`6/2002 Ll!nas'Brunet
`273827??? E?
`8888; ?uélsfBnmet
`674557690 B1
`9/2002 Tajnulgan
`’
`’
`27333722; 5%
`18588; aagner
`674957677 B1
`12/2002 Rjéllismn
`675097320 Bl
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`3/2003 Llinas-Brunet
`6552183 B1
`4/2003 Ramasamy
`7
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`.
`675557677 B2
`‘"2003 Petnllo
`272137532 5% 18588; mm”
`676607721 B2 12/2003 Dewassamy
`7
`7
`272337;}? 5%
`8588;‘ gedlier
`676807303 B2
`V2004 Sign;
`676827715 B2
`V2004 Kl k
`676837045 B2
`V2004 Klgzkg
`677037374 B1
`3/2004 Kleckeretal'
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`6/2004 Klecker
`
`7
`
`7
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`‘mg
`
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`
`ommadossl
`
`-
`
`6/2005 Watanabe
`6,908,924 B2
`88882 gchmazl
`8881,88: 8%
`6,962,991 B2 11/2005 Dempcy
`7,018,985 B1
`3/2006 Beyer
`7,018,989 B2
`3/2006 McGulgan
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`33888;; E;
`‘985888 8211512113
`7’601’820 B2 “mm W
`’
`’
`ang
`2001/0034440 A1 10/2001 Shepard
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`5/2002 Averett
`2002/0198173 A1 12/2002 Schinazi
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`2004/0006007 A1
`1/2004 Gosselin
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`V2004 Eldmp
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`3/2004 Cook
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`4/2004 Sommadossi
`4/2004 Bhat
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`2004/0072788 A1
`4/2004 Bhat
`2004/0097461 A1
`5/2004 Sommadossi
`2004/0097462 A1
`5/2004 Sommadossi
`2004/0101535 A1
`5/2004 Sommadossi
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`2005/0137161 A1
`6/2005 serrrrrraelessi
`2005/0148534 A1
`7/2005 Castelllno
`58828183888 2}
`85882 88mg
`Se-n
`2005/0215513 A1
`9/2005 Boojamra
`2005/0227947 A1 10/2005 Chan
`2005/0261237 A1 11/2005 Boojamra
`2005/0267018 A1 12/2005 Blatt
`2006/0003951 A1
`1/2006 Mekouar
`2006/0014943 A1
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`2006/0035866 A1
`2/2006 CarrrriZZare
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`2/2006 Martln
`2006/0040927 A1
`2/2006 Blake
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`2/2006 Gosselin
`2006/0079478 A1
`4/2006 Boojamra
`
`2004/0102414 A1
`
`5/2004 Somlnadossi
`
`8/2004 Devos
`6,784,166 B2
`9/2004 Li
`6,787,305 B1
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`6,787,526 B1
`6,815,542 B2 11/2004 Hong
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`1/2005 Martin
`6,897,201 B2
`5/2005 Boyer
`
`2006/0122146 A1
`2006/0122154 A1
`2006/0142238 A1
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`2006/0194749 A1
`2006/0199783 A1
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`6/2006 Chun
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