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1. 发明申请

US20100273732A1 COMBINATION METHODS OF TREATING CANCER 审中-公开
标题翻译：治疗癌症的组合方法
公开(公告)号：US20100273732A1
公开(公告)日：2010-10-28
申请号：US12829740
申请日：2010-07-02
申请人： Nicholas G. Bacopoulos , Judy H. Chiao , Paul A. Marks , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon , Richard A. Rifkind
发明人： Nicholas G. Bacopoulos , Judy H. Chiao , Paul A. Marks , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon , Richard A. Rifkind
IPC分类号： A61K31/7068 , A61P35/02 , A61P35/00
CPC分类号： A61K45/06 , A61K9/0019 , A61K31/167 , A61K31/19 , A61K31/522 , A61K31/57 , A61K31/7068 , A61K31/7072 , A61K38/00 , A61K2300/00
摘要： The present invention relates to a method of treating cancer in a subject in need thereof, by administering to a subject in need thereof a first amount of a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or hydrate thereof, in a first treatment procedure, and a second amount of an anti-cancer agent in a second treatment procedure. The first and second amounts together comprise a therapeutically effective amount. The effect of the HDAC inhibitor and the anti-cancer agent may be additive or synergistic.
摘要翻译：本发明涉及在有需要的受试者中治疗癌症的方法，通过在有需要的受试者的第一处理方法中施用第一量的组蛋白脱乙酰酶（HDAC）抑制剂或其药学上可接受的盐或水合物，以及第二处理程序中的第二量的抗癌剂。第一和第二量一起包括治疗有效量。 HDAC抑制剂和抗癌剂的作用可以是相加的或协同的。

2. 发明申请

US20080249179A1 Methods of treating cancer with HDAC inhibitors 审中-公开
公开(公告)号：US20080249179A1
公开(公告)日：2008-10-09
申请号：US11981500
申请日：2007-10-30
申请人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon , William Kevin Kelly
发明人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon , William Kevin Kelly
IPC分类号： A61K31/195 , A61P35/04
CPC分类号： A61K31/19 , A61K31/44 , A61K38/12
摘要： The present invention relates to methods of treating cancers, e.g., leukemia. More specifically, the present invention relates to methods of treating acute and chronic leukemias including Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Chronic Lymphocytic leukemia (CLL), Chronic myeloid leukemia (CML) and Hairy Cell Leukemia, by administration of pharmaceutical compositions comprising HDAC inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The oral formulations of the pharmaceutical compositions have favorable pharmacokinetic profiles such as high bioavailability and surprisingly give rise to high blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

3. 发明授权

US07399787B2 Methods of treating cancer with HDAC inhibitors 有权
标题翻译：用HDAC抑制剂治疗癌症的方法
公开(公告)号：US07399787B2
公开(公告)日：2008-07-15
申请号：US10616649
申请日：2003-07-09
申请人： Judy H. Chiao , Nicholas G. Bacopoulos , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
发明人： Judy H. Chiao , Nicholas G. Bacopoulos , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
IPC分类号： A61K31/19
CPC分类号： A61K9/4866 , A61K9/0019 , A61K9/1652 , A61K31/13 , A61K31/164 , A61K31/165 , A61K31/19 , A61K31/44 , A61K38/12 , A61K47/12 , A61K47/38
摘要： The present invention provides methods of treating cancers, chemoprevention, selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.
摘要翻译：本发明提供了通过施用包含有效的HDAC抑制剂的药物组合物来治疗癌症，化学预防，选择性诱导肿瘤细胞的终末分化，细胞生长停滞和/或细胞凋亡和/或抑制组蛋白脱乙酰酶（HDAC）的方法。本发明的药物组合物中活性化合物的口服生物利用度令人惊奇的高。此外，药物组合物在长时间内意外地引起活性化合物的高，治疗有效的血液水平。本发明进一步提供这些药物组合物的安全的每日给药方案，其易于遵循，并且其在体内导致治疗有效量的HDAC抑制剂。

4. 发明授权

US07148257B2 Methods of treating mesothelioma with suberoylanilide hydroxamic acid 有权
标题翻译：用辛二酰苯胺异羟肟酸治疗间皮瘤的方法
公开(公告)号：US07148257B2
公开(公告)日：2006-12-12
申请号：US10650025
申请日：2003-08-26
申请人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
发明人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
IPC分类号： A61K31/165
CPC分类号： A61K9/4866 , A61K9/0019 , A61K9/1652 , A61K31/13 , A61K31/165 , A61K31/19 , A61K31/44 , A61K47/12 , A61K47/38
摘要： Methods for treating mesothelioma comprising administering the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) are disclosed.
摘要翻译：公开了用于治疗间皮瘤的方法，包括给予组蛋白脱乙酰酶抑制剂辛二酰苯胺异羟肟酸（SAHA）。

5. 发明授权

US07375137B2 Methods of treating cancer with HDAC inhibitors 有权
公开(公告)号：US07375137B2
公开(公告)日：2008-05-20
申请号：US11391971
申请日：2006-03-28
申请人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
发明人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
IPC分类号： A61K31/165
CPC分类号： A61K9/4866 , A61K9/0019 , A61K9/1652 , A61K31/13 , A61K31/165 , A61K31/19 , A61K31/44 , A61K47/12 , A61K47/38
摘要： The present invention provides methods of treating cancers, chemoprevention, selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

6. 发明申请

US20090012175A1 Methods of treating cancer with HDAC inhibitors 审中-公开
标题翻译：用HDAC抑制剂治疗癌症的方法
公开(公告)号：US20090012175A1
公开(公告)日：2009-01-08
申请号：US12217843
申请日：2008-07-08
申请人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
发明人： Nicholas G. Bacopoulos , Judy H. Chiao , Thomas A. Miller , Carolyn M. Paradise , Victoria M. Richon
IPC分类号： A61K31/192 , A61P35/00
CPC分类号： A61K31/16 , A61K31/185
摘要： The present invention provides methods of treating cancers, chemoprevention, selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.
摘要翻译：本发明提供了通过施用包含有效的HDAC抑制剂的药物组合物来治疗癌症，化学预防，选择性诱导肿瘤细胞的终末分化，细胞生长停滞和/或细胞凋亡和/或抑制组蛋白脱乙酰酶（HDAC）的方法。本发明的药物组合物中活性化合物的口服生物利用度令人惊奇的高。此外，药物组合物在长时间内意外地引起活性化合物的高，治疗有效的血液水平。本发明进一步提供这些药物组合物的安全的每日给药方案，其易于遵循，并且其在体内导致治疗有效量的HDAC抑制剂。

7. 发明申请

US20080227862A1 Methods of treating cancer with HDAC inhibitors 审中-公开
标题翻译：用HDAC抑制剂治疗癌症的方法
公开(公告)号：US20080227862A1
公开(公告)日：2008-09-18
申请号：US11980994
申请日：2007-10-30
申请人： Victoria M. Richon , Judy H. Chiao , Thomas A. Miller , Nicholas G. Bacopoulos , Carolyn M. Paradise
发明人： Victoria M. Richon , Judy H. Chiao , Thomas A. Miller , Nicholas G. Bacopoulos , Carolyn M. Paradise
IPC分类号： A61K31/167 , A61P19/00
CPC分类号： A61K31/19 , A61K31/44 , A61K38/12
摘要： The present invention relates to methods of treating cancers, e.g., leukemia. More specifically, the present invention relates to methods of treating acute and chronic leukemias including Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Chronic Lymphocytic leukemia (CLL), Chronic myeloid leukemia (CML) and Hairy Cell Leukemia, by administration of pharmaceutical compositions comprising HDAC inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The oral formulations of the pharmaceutical compositions have favorable pharmacokinetic profiles such as high bioavailability and surprisingly give rise to high blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.
摘要翻译：本发明涉及治疗癌症例如白血病的方法。更具体地说，本发明涉及治疗急性和慢性白血病的方法，包括急性淋巴细胞白血病（ALL），急性骨髓性白血病（AML），慢性淋巴细胞白血病（CLL），慢性骨髓性白血病（CML）和毛细胞白血病包含HDAC抑制剂的药物组合物，例如辛二酰苯胺异羟肟酸（SAHA）。药物组合物的口服制剂具有有利的药代动力学特征，例如高生物利用度，并且令人惊讶地在长时间内引起活性化合物的高血药浓度。本发明进一步提供这些药物组合物的安全的每日给药方案，其易于遵循，并且其在体内导致治疗有效量的HDAC抑制剂。

8. 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.

9. 发明授权

US07799803B2 Hydroxamic acid compounds and methods of use thereof 失效
标题翻译：羟肟酸化合物及其使用方法
公开(公告)号：US07799803B2
公开(公告)日：2010-09-21
申请号：US11710036
申请日：2007-02-22
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： A61K31/04 , C07D215/38
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.
摘要翻译：本发明涉及一类具有至少两个含芳基基团的异羟肟酸衍生物，其中至少一个是喹啉基，异喹啉基或苄基部分，通过亚甲基链与异羟肟酸基团连接。异羟肟酸化合物可用于治疗癌症，例如脑癌。异羟肟酸化合物也可以抑制组蛋白脱乙酰酶，适用于选择性诱导终末分化，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

10. 发明授权

US07126001B2 Class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof 有权
标题翻译：细胞分化剂和组蛋白脱乙酰酶抑制剂的类别及其使用方法
公开(公告)号：US07126001B2
公开(公告)日：2006-10-24
申请号：US10281875
申请日：2002-10-25
申请人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas A. Miller , Paul A. Marks , Victoria M. Richon , Richard A. Rifkind
发明人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas A. Miller , Paul A. Marks , Victoria M. Richon , Richard A. Rifkind
IPC分类号： C07D215/38 , C07D473/02 , C07C259/04 , A61K31/47
CPC分类号： C07D213/75 , C07C233/07 , C07C233/13 , C07C235/74 , C07C237/12 , C07C237/22 , C07C259/06 , C07C271/22 , C07C311/03 , C07C311/06 , C07C311/42 , C07C327/32 , C07C2601/14 , C07D213/82 , C07D215/38 , C07D215/40 , C07D215/54 , C07D231/12 , C07D231/40 , C07D233/56 , C07D233/64 , C07D249/08 , C07D277/46 , C07D333/38 , C07F9/2458 , C07F9/4465
摘要： The present invention provides the compound having the formula: wherein each of R1 and R2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH2—; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.
摘要翻译：本发明提供具有下式的化合物：其中R 1和R 2各自为取代或未取代的芳基，环烷基，环烷基氨基，石脑油，吡啶氨基，哌啶子基，叔丁基，芳氧基，芳基烷氧基或吡啶基; 其中A是酰氨基部分，-O - ， - S - ， - NH-或-CH 2 - 。并且其中n为3至8的整数。本发明还提供了选择性诱导肿瘤细胞的生长停滞，末端分化和/或凋亡并从而抑制这些细胞增殖的方法。此外，本发明提供了治疗具有以肿瘤细胞增殖为特征的肿瘤的患者的方法。最后，本发明提供包含药学上可接受的载体和治疗上可接受量的上述化合物的药物组合物。

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