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1. 发明授权

US07795304B2 Histone deacetylase inhibitors 有权
标题翻译：组蛋白脱乙酰酶抑制剂
公开(公告)号：US07795304B2
公开(公告)日：2010-09-14
申请号：US11660718
申请日：2005-08-22
申请人： Sandro Belvedere , Christopher Laurence Hamblett , Thomas A. Miller , David J. Witter , Jiaming Yan
发明人： Sandro Belvedere , Christopher Laurence Hamblett , Thomas A. Miller , David J. Witter , Jiaming Yan
IPC分类号： C07C271/20 , C07D295/088 , C07D277/46 , C07D213/30 , A61K31/5375 , A61K31/4402 , A61K31/4168 , A61K31/40 , A61K31/325
CPC分类号： C07D295/088 , C07C271/22 , C07D277/46
摘要： The invention relates to hydroxamic acid derivatives having carbamate linkage with the structural formula that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous systems (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.
摘要翻译：本发明涉及具有结构式的具有氨基甲酸酯键的异羟肟酸衍生物，其为组蛋白脱乙酰酶（HDAC）的抑制剂，可用于预防和/或治疗细胞增殖性疾病，例如癌症，自身免疫性，过敏性和炎性疾病，中枢神经系统疾病（CNS）如神经变性疾病，以及预防和/或治疗再狭窄。

2. 发明授权

US07737184B2 Histone deacetylase inhibitors 有权
标题翻译：组蛋白脱乙酰酶抑制剂
公开(公告)号：US07737184B2
公开(公告)日：2010-06-15
申请号：US11629447
申请日：2005-07-08
申请人： Sandro Belvedere , Christopher Laurence Hamblett , Thomas A. Miller , David J. Witter , Jiaming Yan
发明人： Sandro Belvedere , Christopher Laurence Hamblett , Thomas A. Miller , David J. Witter , Jiaming Yan
IPC分类号： A61K31/167 , C07C233/31
CPC分类号： C07D295/215 , C07C275/24 , C07C275/26 , C07C275/28 , C07C275/36 , C07C335/08 , C07C335/16 , C07C335/18 , C07C2601/02 , C07C2601/14 , C07C2603/18 , C07D277/46
摘要： This invention relates to hydroxamic acid derivatives having a urea linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.
摘要翻译：本发明涉及具有尿素键的异羟肟酸衍生物，其是组蛋白脱乙酰酶（HDAC）的抑制剂，并且可用于预防和/或治疗细胞增殖性疾病，例如癌症，自身免疫性，过敏性和炎性疾病，疾病中枢神经系统（CNS）如神经变性疾病，以及预防和/或治疗再狭窄。

3. 发明申请

US20090118291A1 Histone deacetylase inhibitors 有权
标题翻译：组蛋白脱乙酰酶抑制剂
公开(公告)号：US20090118291A1
公开(公告)日：2009-05-07
申请号：US11660718
申请日：2005-08-22
申请人： Sandro Belvedere , Christopher Laurence Hamblett , Thomas A. Miller , David J. Witter , Jiaming Yan
发明人： Sandro Belvedere , Christopher Laurence Hamblett , Thomas A. Miller , David J. Witter , Jiaming Yan
IPC分类号： A61K31/5377 , C07D277/20 , A61K31/426 , C07C271/06 , A61K31/44 , A61K31/40 , A61P35/00 , C07D207/08 , C07D213/55 , A61K31/325 , C07D295/18
CPC分类号： C07D295/088 , C07C271/22 , C07D277/46
摘要： This invention relates to hydroxamic acid derivatives having a carbamate linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.
摘要翻译：本发明涉及具有氨基甲酸酯键的异羟肟酸衍生物，其是组蛋白脱乙酰酶（HDAC）的抑制剂，可用于预防和/或治疗细胞增殖性疾病，例如癌症，自身免疫性，过敏性和炎性疾病，疾病中枢神经系统（CNS）如神经变性疾病，以及预防和/或治疗再狭窄。

4. 发明授权

US07534918B2 Histone deacetylase inhibitors 有权
标题翻译：组蛋白脱乙酰酶抑制剂
公开(公告)号：US07534918B2
公开(公告)日：2009-05-19
申请号：US11629449
申请日：2005-07-08
申请人： Sandro Belvedere , Joey Lee Methot , Thomas A. Miller , David J. Witter , Jiaming Yan
发明人： Sandro Belvedere , Joey Lee Methot , Thomas A. Miller , David J. Witter , Jiaming Yan
IPC分类号： C07C259/04 , A61K31/19
CPC分类号： C07C311/42 , C07C311/13 , C07C311/19 , C07C311/24 , C07C311/29 , C07D215/36 , C07D277/46 , C07D333/34 , C07D417/12
摘要： This invention relates to hydroxamic acid derivatives having a sulfonamide linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.
摘要翻译：本发明涉及具有磺酰胺键的异羟肟酸衍生物，其是组蛋白脱乙酰酶（HDAC）的抑制剂，可用于预防和/或治疗细胞增殖性疾病，例如癌症，自身免疫性，过敏性和炎性疾病，疾病中枢神经系统（CNS）如神经变性疾病，以及预防和/或治疗再狭窄。

5. 发明申请

US20090023718A1 Diamine and Iminodiacetic Acid Hydroxamic Acid Derivatives 审中-公开
标题翻译：二胺和亚氨基二乙酸羟肟酸衍生物
公开(公告)号：US20090023718A1
公开(公告)日：2009-01-22
申请号：US10580480
申请日：2004-11-23
申请人： Thomas A. Miller , David J. Witter , Sandro Belvedere
发明人： Thomas A. Miller , David J. Witter , Sandro Belvedere
IPC分类号： A61K31/5355 , A61K31/416 , A61K31/47 , A61K31/4965 , C07D231/54 , C07D215/38 , C07D265/30 , C07D241/04 , A61P35/00
CPC分类号： C07D211/16 , C07C259/06 , C07C2601/14 , C07D209/14 , C07D215/38 , C07D215/40 , C07D217/06 , C07D231/56 , C07D277/82 , C07D295/185 , C07D317/66
摘要： The present invention relates to a novel class of hydroxamic acid derivatives having a diamine or iminodiacetic acid backbone. 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 including terminal differentiation, arresting cell growth and/or apoptosis of neo-plastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compound 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.
摘要翻译：本发明涉及具有二胺或亚氨基二乙酸骨架的新一类异羟肟酸衍生物。异羟肟酸化合物可用于治疗癌症。异羟肟酸化合物还可以抑制组蛋白脱乙酰酶，并且适用于选择性地包括末端分化，阻止新塑料细胞的细胞生长和/或细胞凋亡，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，例如神经变性疾病本发明进一步提供包含异羟肟酸衍生物的药物组合物，以及易于遵循的这些药物组合物的安全的给药方案，并且其在体内导致治疗有效量的异羟肟酸衍生物。

6. 发明授权

US08227636B2 Histone deacetylase inhibitor prodrugs 有权
标题翻译：组蛋白脱乙酰酶抑制剂前药
公开(公告)号：US08227636B2
公开(公告)日：2012-07-24
申请号：US10594483
申请日：2005-04-05
申请人： Thomas A. Miller , David J. Witter , Sandro Belvedere
发明人： Thomas A. Miller , David J. Witter , Sandro Belvedere
IPC分类号： C07C69/02 , A61K31/22
CPC分类号： C07D213/80 , C07C259/06 , C07C271/22 , C07D213/82 , C07D215/38 , C07D215/40 , C07D215/42
摘要： The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (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.
摘要翻译：本发明涉及基于异羟肟酸的组蛋白脱乙酰酶（HDAC）抑制剂例如辛二酰苯胺异羟肟酸（SAHA）的前药。前药是与游离异羟肟酸相比具有增加的水溶性和细胞渗透性的酰化衍生物，并且可用于抑制HDAC，并且用于选择性诱导肿瘤细胞的终末分化，细胞生长停滞和/或凋亡，由此抑制这些细胞。因此，本发明的前药可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。本发明的前药还可用于预防和治疗硫氧还蛋白（TRX）介导的疾病，如自身免疫，过敏和炎性疾病，以及预防和/或治疗中枢神经系统疾病（CNS），如神经退行性疾病。

7. 发明授权

US07935724B2 Thiophene and benzothiophene hydroxamic acid derivatives 有权
标题翻译：噻吩和苯并噻吩异羟肟酸衍生物
公开(公告)号：US07935724B2
公开(公告)日：2011-05-03
申请号：US10574992
申请日：2004-10-08
申请人： Thomas A. Miller , David J. Witter , Sandro Belvedere
发明人： Thomas A. Miller , David J. Witter , Sandro Belvedere
IPC分类号： A61K31/381 , C07D333/70
CPC分类号： C07D333/66 , C07C259/08 , C07C2602/08 , C07D333/38 , C07D333/70 , C07D409/12 , C07D409/14 , C07D413/12 , C07D417/12
摘要： The present invention relates to a novel class of hydroxamic acid derivatives having a benzothiophene or thiophene backbone. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit historic 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.
摘要翻译：本发明涉及具有苯并噻吩或噻吩主链的新一类异羟肟酸衍生物。异羟肟酸化合物可用于治疗癌症。异羟肟酸化合物还可以抑制历史的脱乙酰酶，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，例如神经变性疾病，本发明进一步提供包含异羟肟酸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异羟肟酸衍生物。

8. 发明申请

US20090023786A1 Histone Deacetylase Inhibitor Prodrugs 有权
标题翻译：组蛋白脱乙酰酶抑制剂前药
公开(公告)号：US20090023786A1
公开(公告)日：2009-01-22
申请号：US10594483
申请日：2005-04-05
申请人： Thomas A. Miller , David J. Witter , Sandro Belvedere
发明人： Thomas A. Miller , David J. Witter , Sandro Belvedere
IPC分类号： A61K31/4406 , C07C229/40 , A61K31/216 , A61P35/00 , C07D213/80
CPC分类号： C07D213/80 , C07C259/06 , C07C271/22 , C07D213/82 , C07D215/38 , C07D215/40 , C07D215/42
摘要： The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (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.
摘要翻译：本发明涉及基于异羟肟酸的组蛋白脱乙酰酶（HDAC）抑制剂例如辛二酰苯胺异羟肟酸（SAHA）的前药。前药是与游离异羟肟酸相比具有增加的水溶性和细胞渗透性的酰化衍生物，并且可用于抑制HDAC，并且用于选择性诱导肿瘤细胞的终末分化，细胞生长停滞和/或凋亡，由此抑制这些细胞。因此，本发明的前药可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。本发明的前药还可用于预防和治疗硫氧还蛋白（TRX）介导的疾病，如自身免疫，过敏和炎性疾病，以及预防和/或治疗中枢神经系统疾病（CNS），如神经退行性疾病。

9. 发明授权

US07507858B2 Histone deacetylase inhibitors 有权
标题翻译：组蛋白脱乙酰酶抑制剂
公开(公告)号：US07507858B2
公开(公告)日：2009-03-24
申请号：US11629448
申请日：2005-07-15
申请人： Sandro Belvedere , Thomas A. Miller , David J. Witter
发明人： Sandro Belvedere , Thomas A. Miller , David J. Witter
IPC分类号： C07C259/04
CPC分类号： C07C259/06 , A61K31/16 , A61K31/185 , A61K31/426 , A61K31/47 , C07D215/40 , C07D277/82
摘要： This invention relates to iminodiacetic acid and diamine hydroxamic acid derivatives, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.
摘要翻译：本发明涉及亚氨基二乙酸和二胺异羟肟酸衍生物，其是组蛋白脱乙酰酶（HDAC）的抑制剂，可用于预防和/或治疗细胞增殖性疾病，例如癌症，自身免疫性，过敏性和炎性疾病，中枢神经系统（CNS）如神经变性疾病，以及预防和/或治疗再狭窄。

10. 发明授权

US07199134B2 Hydroxamic acid compounds and methods of use thereof 失效
公开(公告)号：US07199134B2
公开(公告)日：2007-04-03
申请号：US10817688
申请日：2004-04-01
申请人： Ronald Breslow , Thomas A. Miller , Sandro Belvedere , Paul A. Marks , Victoria M. Richon , Richard A. Rifkind
发明人： Ronald Breslow , Thomas A. Miller , Sandro Belvedere , Paul A. Marks , Victoria M. Richon , Richard A. Rifkind
IPC分类号： C07D215/38 , C07D215/36 , A61K31/47 , A61K31/44
CPC分类号： C07D211/02 , C07D215/38 , C07D401/12
摘要： The present invention relates to a novel class of hydroxamic acid derivatives having at least two aryl containing groups, at least one of which is a quinolinyl, isoquinolinyl or benzyl moiety, linked to the hydroxamic acid group through a methylene chain. The hydroxamic acid compounds can be used to treat cancer, for example, brain 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 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.

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