公开(公告)号：EP1991226A2

公开(公告)日：2008-11-19

申请号：EP07751483.4

申请日：2007-02-23

申请人： Merck & Co., Inc.

发明人： GRIMM, Jonathan, B. ,  HUBBS, Jed, L. ,  MILLER, Thomas ,  OTTE, Karin, M. ,  SILIPHAIVANH, Phieng ,  STANTON, Matthew, G. ,  WILSON, Kevin ,  WITTER, David ,  ZHOU, Hua

IPC分类号： A61K31/4439

CPC分类号： C07C237/42 ,  C07D333/20

摘要： The present invention relates to a novel class of compounds. 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：EP2121633A2

公开(公告)日：2009-11-25

申请号：EP08709605.3

申请日：2008-02-11

申请人： Merck & Co., Inc. ,  Merck Sharp & Dohme Limited

发明人： BLURTON, PETER ,  FLETCHER, Stephen ,  TEALL, Martin ,  HARRISON, Timothy ,  MUNOZ, Benito ,  RIVKIN, Alexey ,  HAMBLETT, Christopher ,  SILIPHAIVANH, Phieng ,  OTTE, Karin

IPC分类号： C07D239/48 ,  C07D239/50 ,  C07D401/02 ,  C07D401/14 ,  A61K31/506 ,  A61P25/00 ,  C07D401/04 ,  C07D401/06 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/04 ,  C07D471/04 ,  C07D487/04

CPC分类号： C07D403/04 ,  C07D213/74 ,  C07D213/81 ,  C07D213/82 ,  C07D239/48 ,  C07D239/95 ,  C07D241/20 ,  C07D285/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D495/04

摘要： Compounds of formula (I) selectively inhibitproduction of Aβ(1-42) and hence find use in treatment of Alzheimer's disease and other conditions associated with deposition ofA(β) in the brain.

公开(公告)号：EP2013196A2

公开(公告)日：2009-01-14

申请号：EP07755785.8

申请日：2007-04-20

申请人： Merck & Co., Inc.

发明人： HEIDEBRECHT, Richard ,  METHOT, Joey ,  MAMPREIAN, Dawn ,  MILLER, Thomas ,  SILIPHAIVANH, Phieng

IPC分类号： C07D333/24 ,  A61K31/381

CPC分类号： C07D333/20 ,  C07C229/60 ,  C07C237/04 ,  C07C237/40

摘要： The present invention relates to a novel class of disubstituted aniline compounds. 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：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：EP2049124A2

公开(公告)日：2009-04-22

申请号：EP07810507.9

申请日：2007-07-16

申请人： Merck & Co., Inc.

发明人： CLOSE, Joshua ,  GRIMM, Jonathan ,  HEIDEBRECHT, Richard, W., Jr. ,  KATTAR, Solomon ,  MILLER, Thomas, A. ,  OTTE, Karin, M. ,  PETERSON, Scott ,  SILIPHAIVANH, Phieng ,  TEMPEST, Paul ,  WILSON, Kevin, J. ,  WITTER, David, J.

IPC分类号： A61K31/66 ,  A61K31/662 ,  C07F9/40 ,  C07F9/32 ,  C07F9/547 ,  C07F9/6564

CPC分类号： C07F9/655345 ,  C07F9/5304 ,  C07F9/5325 ,  C07F9/65033 ,  C07F9/65586 ,  C07F9/657154 ,  C07F9/657181 ,  C07F9/6584

摘要： The present invention relates to a novel class of phosphorus derivatives. The phosphorus compounds can be used to treat cancer. The phosphorus 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 phosphorus derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the phosphorus derivatives in vivo.

公开(公告)号：EP1896395A2

公开(公告)日：2008-03-12

申请号：EP06785306.9

申请日：2006-06-21

申请人： Merck & Co., Inc.

发明人： GRIMM, Jonathan ,  HARRINGTON, Paul ,  HEIDEBRECHT, Richard, Jr. ,  MILLER, Thomas ,  OTTE, Karin ,  SILIPHAIVANH, Phieng ,  SLOMAN, David ,  STANTON, Matthew ,  WILSON, Kevin ,  WITTER, David ,  KATTAR, Solomon ,  TEMPEST, Paul

IPC分类号： C07C233/02

CPC分类号： C07C235/78 ,  C07C233/75 ,  C07C233/80 ,  C07C235/42 ,  C07C235/56 ,  C07C235/74 ,  C07C235/84 ,  C07C255/60 ,  C07C311/08 ,  C07C311/16 ,  C07C311/46 ,  C07C2602/08 ,  C07D207/06 ,  C07D207/327 ,  C07D209/14 ,  C07D209/20 ,  C07D211/06 ,  C07D213/40 ,  C07D213/56 ,  C07D213/82 ,  C07D215/06 ,  C07D215/12 ,  C07D215/40 ,  C07D231/40 ,  C07D249/08 ,  C07D261/14 ,  C07D265/30 ,  C07D277/28 ,  C07D277/46 ,  C07D277/56 ,  C07D295/135 ,  C07D295/155 ,  C07D295/185 ,  C07D307/68 ,  C07D319/16 ,  C07D319/18 ,  C07D333/20 ,  C07D333/38 ,  C07D333/70 ,  C07D413/14 ,  C07D495/04

摘要： The present invention relates to a novel class of modified malonate derivatives. The modified malonate compounds can be used to treat cancer. The modified malonate 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 modified malonate derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the modified malonate derivatives in vivo.

摘要翻译： 本发明涉及一类新型的丙二酸改性衍生物。 修饰的丙二酸酯化合物可用于治疗癌症。 修饰的丙二酸酯化合物还可以抑制组蛋白脱乙酰酶，并且适用于选择性诱导末端分化，并阻止肿瘤细胞的细胞生长和/或凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性，过敏性和炎性疾病，以及预防和/或治疗中枢神经系统（CNS）的疾病，例如 神经退行性疾病 本发明进一步提供包含改性丙二酸酯衍生物和这些药物组合物的安全投药方案的药物组合物，其易于遵循，并且其在体内导致治疗有效量的修饰的丙二酸酯衍生物。

公开(公告)号：EP1874755A2

公开(公告)日：2008-01-09

申请号：EP06750201.3

申请日：2006-04-14

申请人： Merck & Co., Inc.

发明人： HUBBS, Jed Lee ,  KATTAR, Sam ,  METHOT, Joey ,  MILLER, Thomas ,  SILIPHAIVANH, Phieng ,  STANTON, Matthew ,  WILSON, Kevin ,  WITTER, David, J.

IPC分类号： C07D333/56 ,  C07D271/10 ,  A61K31/38 ,  A61K31/41

CPC分类号： C07D333/70 ,  A61K31/38 ,  A61K31/381 ,  A61K31/41

摘要： The present invention relates to a novel class of hydroxamic acid derivatives. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid 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 are also 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.