公开(公告)号：EP1556399A2

公开(公告)日：2005-07-27

申请号：EP03751791.9

申请日：2003-07-11

申请人： Merck & Co., Inc. ,  Isis Pharmaceuticals, Inc.

发明人： BHAT, Balkrishen ,  CARROLL, Steven, S. ,  ELDRUP, Anne, B. ,  MACCOSS, Malcolm ,  OLSEN, David, B. ,  PRAKASH, Thazha, P.

IPC分类号： C07H19/14 ,  A61K31/70

CPC分类号： C07H19/14 ,  C07H19/22

摘要： The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

公开(公告)号：EP1551421A2

公开(公告)日：2005-07-13

申请号：EP03751777.8

申请日：2003-06-17

申请人： Merck & Co., Inc. ,  Isis Pharmaceuticals, Inc.

发明人： CARROLL, Steven, S. ,  OLSEN, David, B. ,  DURETTE, Philippe, L. ,  BHAT, Balkrishen ,  DANDE, Prasad ,  ELDRUP, Anne, B.

IPC分类号： A61K31/70 ,  C07H19/06 ,  C07H19/10 ,  C07H19/167 ,  C07H19/20

CPC分类号： C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/12 ,  C07H19/16 ,  C07H19/167 ,  C07H19/20

摘要： The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

公开(公告)号：EP1539188A2

公开(公告)日：2005-06-15

申请号：EP02709095.0

申请日：2002-01-18

申请人： Merck & Co., Inc. ,  ISIS PHARMACEUTICALS, INC.

发明人： CARROLL, Steven, S. ,  LAFEMINA, Robert, L. ,  HALL, Dawn, L. ,  HIMMELBERGER, Amy, L. ,  KUO, Lawrence, C. ,  MACCOSS, Malcolm ,  OLSEN, David, B. ,  RUTKOWSKI, Carrie, A. ,  TOMASSINI, Joanne, E. ,  AN, Haoyun ,  BHAT, Balkrishen ,  BHAT, Neelima ,  COOK, Phillip, Dan ,  ELDRUP, Anne, B. ,  GUINOSSO, Charles, J. ,  PRHAVC, Marija ,  PRAKASH, Thazha, P.

IPC分类号： A61K31/70 ,  A61K31/712 ,  A61K31/7105

CPC分类号： C07H19/16 ,  A61K9/4858 ,  A61K31/7056 ,  A61K31/7064 ,  A61K31/7076 ,  A61K38/21 ,  A61K45/06 ,  C07D473/00 ,  C07D487/04 ,  C07H19/00 ,  C07H19/06 ,  C07H19/10 ,  C07H19/12 ,  C07H19/14 ,  C07H19/20 ,  Y02P20/582 ,  A61K2300/00

摘要： The present invention provides nucleoside derivatives which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside derivatives alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside derivatives of the present invention.

公开(公告)号：EP1476169A1

公开(公告)日：2004-11-17

申请号：EP03707772.4

申请日：2003-02-07

申请人： Merck & Co., Inc. ,  ISIS PHARMACEUTICALS, INC.

发明人： OLSEN, David, B. ,  LAFEMINA, Robert, L. ,  ELDRUP, Anne, B. ,  BERA, Sanjib

IPC分类号： A61K31/7052 ,  A61K31/7076 ,  A61K31/708

CPC分类号： A61K31/7064 ,  A61K31/519 ,  A61K31/52 ,  A61K31/522 ,  A61K31/655 ,  A61K31/7068 ,  A61K31/7076 ,  A61K31/708 ,  A61K45/06

摘要： The present invention provides methods of inhibiting orthopoxvirus replication and/or treating orthopoxvirus infection with certain nucleoside compounds and derivatives thereof. These compounds are particularly useful as inhibitors of vaccinia virus and variola virus replication and/or for the treatment of vaccinia virus and variola virus infection. The nucleoside compounds may be administered alone or in combination with other agents active against orthopoxvirus infection, in particular against vaccinia virus or variola virus infection. Another aspect of the present invention provides for the use of such nucleoside compounds in the manufacture of a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection. Yet a further aspect of the present invention provides such nucleoside compounds for use as a medicament for the inhibition of orthopoxvirus replication and/or for the treatment of orthopoxvirus infection.

公开(公告)号：EP1355916A2

公开(公告)日：2003-10-29

申请号：EP02709299.8

申请日：2002-01-18

申请人： Merck & Co., Inc. ,  ISIS PHARMACEUTICALS, INC.

发明人： CARROLL, Steven, S. ,  MACCOSS, Malcolm ,  OLSEN, David, B. ,  BHAT, Balkrishen ,  BHAT, Neelima ,  COOK, Phillip Dan ,  ELDRUP, Anne, B. ,  PRAKASH, Thazha, P. ,  PRHAVC, Marija ,  SONG, Quanlai

IPC分类号： C07H19/14 ,  A61K31/7064 ,  A61P31/14

CPC分类号： C07H19/16 ,  A61K9/4858 ,  A61K31/7056 ,  A61K31/7064 ,  A61K31/7076 ,  A61K38/21 ,  A61K45/06 ,  C07D473/00 ,  C07D487/04 ,  C07H19/00 ,  C07H19/06 ,  C07H19/10 ,  C07H19/12 ,  C07H19/14 ,  C07H19/20 ,  Y02P20/582 ,  A61K2300/00

摘要： The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

公开(公告)号：EP0833945B1

公开(公告)日：2002-01-30

申请号：EP96920611.9

申请日：1996-06-03

申请人： MERCK & CO., INC.

发明人： COLE, James, L. ,  KUO, Lawrence, C. ,  OLSEN, David, B.

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12Q1/6813 ,  C12Q2533/101 ,  C12Q2521/307 ,  C12Q2521/337

摘要： An assay for enzymes which act on substrates to produce a single-stranded oligonucleotide product has been developed which involves the DNA polymerase-catalyzed extension of the oligonucleotide cleavage product using labeled nucleotides and a DNA template containing a 3' region complementary to the oligonucleotide product joined to a 5' region consisting of repeated nucleotide residues. The DNA polymerase extension assay does not involve gel electrophoretic separation and is amenable to high volume screening of potential inhibitors. Other key features of the assay are that it monitors the substrate cleavage reaction only at the correct position in the sequence, thereby discriminating against nonspecific cleavage products, and that it is sensitive enough to detect 200 attomoles of product.

公开(公告)号：EP0832292A1

公开(公告)日：1998-04-01

申请号：EP96920610.0

申请日：1996-06-03

申请人： MERCK & CO., INC.

发明人： COLE, James, L. ,  KUO, Lawrence, C. ,  OLSEN, David, B.

IPC分类号： C12Q1

CPC分类号： C12Q1/701 ,  C12Q1/6846 ,  C12Q2533/101 ,  C12Q2521/307

摘要： An assay for the influenza virus endonuclease has been developed which involves DNA polymerase-catalyzed extension of the viral endonuclease cleavage product using labeled nucleotides and a DNA template containing a 3' region complementary to the product joined to a 5' region consisting of repeated residues. The DNA polymerase coupled assay does not involve gel electrophoretic separation and is amenable to high volume screening of potential inhibitors. Another key feature of the assay is that it is sensitive enoughto detect 200 attomoles of product.