公开(公告)号：EP1954698B1

公开(公告)日：2009-06-24

申请号：EP06837965.0

申请日：2006-11-17

申请人： Merck & Co., Inc.

发明人： BERK, Scott, C. ,  CLOSE, Joshua ,  HAMBLETT, Christopher ,  HEIDEBRECHT, Richard, W. ,  KATTAR, Solomon, D. ,  KLIMAN, Laura, T. ,  MAMPREIAN, Dawn, M. ,  METHOT, Joey, L. ,  MILLER, Thomas ,  SLOMAN, David, L. ,  STANTON, Matthew, G. ,  TEMPEST, Paul ,  ZABIEREK, Anna, A.

IPC分类号： C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D498/10 ,  A61K31/438 ,  A61K31/407 ,  A61K31/424 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00

CPC分类号： C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D491/107 ,  C07D498/10

公开(公告)号：EP2063710A2

公开(公告)日：2009-06-03

申请号：EP07837578.9

申请日：2007-08-31

申请人： Merck & Co., Inc.

发明人： STANTON, Matthew, G. ,  MUNOZ, Benito ,  SLOMAN, David, L. ,  HUBBS, Jed ,  HAMBLETT, Christopher

IPC分类号： A01N43/40 ,  A61K31/435 ,  C07D211/34

CPC分类号： C07D211/38

摘要： Compounds of formula (I). Selectively inhibit production of Aβ(1-42) and hence find use in treatment of diseases associated with deposition of β-amyloid in the brain.

公开(公告)号：EP1954698A1

公开(公告)日：2008-08-13

申请号：EP06837965.0

申请日：2006-11-17

申请人： Merck & Co., Inc.

发明人： BERK, Scott, C. ,  CLOSE, Joshua ,  HAMBLETT, Christopher ,  HEIDEBRECHT, Richard, W. ,  KATTAR, Solomon, D. ,  KLIMAN, Laura, T. ,  MAMPREIAN, Dawn, M. ,  METHOT, Joey, L. ,  MILLER, Thomas ,  SLOMAN, David, L. ,  STANTON, Matthew, G. ,  TEMPEST, Paul ,  ZABIEREK, Anna, A.

IPC分类号： C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D498/10 ,  A61K31/438 ,  A61K31/407 ,  A61K31/424 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00

CPC分类号： C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D491/107 ,  C07D498/10

摘要： The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR12, NRla, C(O) and O; E is selected from a bond, CR12. NR1 a, C(O) and O; wherein at least one of A, B, D or E is CR12; and provided that when A is O, then E is not O; G is CRl2; R is selected from NH2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

公开(公告)号：EP1945028A2

公开(公告)日：2008-07-23

申请号：EP06826996.8

申请日：2006-10-30

申请人： Merck & Co., Inc.

发明人： HAMBLETT, Christopher ,  MAMPREIAN, Dawn, M. ,  METHOT, Joey, L. ,  MILLER, Thomas ,  SLOMAN, David, L. ,  STANTON, Matthew, G. ,  WILSON, Kevin

IPC分类号： A01N43/40 ,  A61K31/44

CPC分类号： C07D213/56 ,  C07D239/28 ,  C07D401/12 ,  C07D487/08

摘要： The present invention relates to a novel class of substituted nicotinamides.. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

公开(公告)号：EP1976511A2

公开(公告)日：2008-10-08

申请号：EP07762514.3

申请日：2007-01-09

申请人： Merck & Co., Inc.

发明人： MILLER, Thomas, A. ,  SLOMAN, David, L. ,  STANTON, Matthew, G. ,  WILSON, Kevin, J. ,  WITTER, David, J.

IPC分类号： A61K31/38

CPC分类号： C07D231/40 ,  C07D333/20 ,  C07D333/70 ,  C07D409/12 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14

摘要： The present invention relates to a novel class of fluorinated arylamide derivatives. The instant compounds can be used to treat cancer. The fluorinated arylamide derivatives can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

公开(公告)号：EP1874295A1

公开(公告)日：2008-01-09

申请号：EP06750228.6

申请日：2006-04-14

申请人： Merck & Co., Inc. ,  Aton Pharma, Inc.

发明人： HUBBS, Jed, Lee ,  MAMPREIAN, Dawn, M. ,  METHOT, Joey, L. ,  MILLER, Thomas, A. ,  OTTE, Karin, M. ,  SILIPHAIVANH, Phieng ,  SLOMAN, David, L. ,  STANTON, Matthew, G. ,  WILSON, Kevin, J. ,  WITTER, David, J.

IPC分类号： A61K31/38 ,  C07D333/22

CPC分类号： C07D333/70 ,  C07D409/06 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14

摘要： The present invention relates to a novel class of benzothiophene amide derivatives. The hydroxamic acid compounds can be used to treat cancer. The benzothiophene amide compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

公开(公告)号：EP2320737A1

公开(公告)日：2011-05-18

申请号：EP09805356.4

申请日：2009-07-27

申请人： Merck & Co., Inc.

发明人： KATZ, Jason ,  KNOWLES, Sandra, L. ,  JEWELL, James, P. ,  SLOMAN, David, L. ,  STANTON, Matthew, G. ,  NOUCTI, Njamkou

IPC分类号： A01N43/78 ,  A61K31/425

CPC分类号： A61K31/425 ,  C07D417/04 ,  C07D417/14

摘要： The invention encompasses pyrazolo[1,5-a]pyridine derivatives which selectively inhibit microtubule affinity regulating kinase (MARK) and are therefore useful for the treatment or prevention of Alzheimer's disease. Pharmaceutical compositions and methods of use are also included.