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1. 发明申请

US20060009527A1 Method of treating TRX mediated diseases 审中-公开
公开(公告)号：US20060009527A1
公开(公告)日：2006-01-12
申请号：US11223547
申请日：2005-09-09
申请人： Victoria Richon , Paul Marks , Richard Rifkind , Lisa Butler
发明人： Victoria Richon , Paul Marks , Richard Rifkind , Lisa Butler
IPC分类号： A61K31/19
CPC分类号： A61K31/4406 , A61K31/00 , A61K31/12 , A61K31/121 , A61K31/16 , A61K31/165 , A61K31/166 , A61K31/19 , A61K31/192 , A61K38/12 , A61K38/15
摘要： The present invention provides a novel method for treating and/or preventing thioredoxin (TRX)-mediated diseases and conditions, by administering to a subject in need of such treatment a therapeutically effective amount of a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or hydrate thereof. The HDAC inhibitor can alter the expression of a thioredoxin-binding-protein (e.g. TBP-2), which in turn can lead to an altered TRX/thioredoxin-binding-protein cellular binding interaction, resulting in an increase or decrease in the level or activity of cellular TRX, for example the expression level or reducing activity of TRX. Thus the present invention relates to the use of HDAC inhibitors in a method of preventing and/or treating a wide variety of thioredoxin (TRX)-mediated diseases and conditions, such as inflammatory diseases, allergic diseases, autoimmune diseases, diseases associated with oxidative stress or diseases characterized by cellular hyperproliferation.

2. 发明申请

US20060009526A1 Method of treating TRX mediated diseases 审中-公开
公开(公告)号：US20060009526A1
公开(公告)日：2006-01-12
申请号：US11223405
申请日：2005-09-09
申请人： Victoria Richon , Paul Marks , Richard Rifkind , Lisa Butler
发明人： Victoria Richon , Paul Marks , Richard Rifkind , Lisa Butler
IPC分类号： A61K31/19
CPC分类号： A61K31/4406 , A61K31/00 , A61K31/12 , A61K31/121 , A61K31/16 , A61K31/165 , A61K31/166 , A61K31/19 , A61K31/192 , A61K38/12 , A61K38/15
摘要： The present invention provides a novel method for treating and/or preventing thioredoxin (TRX)-mediated diseases and conditions, by administering to a subject in need of such treatment a therapeutically effective amount of a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or hydrate thereof. The HDAC inhibitor can alter the expression of a thioredoxin-binding-protein (e.g. TBP-2), which in turn can lead to an altered TRX/thioredoxin-binding-protein cellular binding interaction, resulting in an increase or decrease in the level or activity of cellular TRX, for example the expression level or reducing activity of TRX. Thus the present invention relates to the use of HDAC inhibitors in a method of preventing and/or treating a wide variety of thioredoxin (TRX)-mediated diseases and conditions, such as inflammatory diseases, allergic diseases, autoimmune diseases, diseases associated with oxidative stress or diseases characterized by cellular hyperproliferation.

3. 发明申请

US20060241129A1 Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof 有权
标题翻译：新型细胞分化剂和组蛋白脱乙酰酶抑制剂及其使用方法
公开(公告)号：US20060241129A1
公开(公告)日：2006-10-26
申请号：US11474043
申请日：2006-06-22
申请人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas Miller , Paul Marks , Victoria Richon , Richard Rifkind
发明人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas Miller , Paul Marks , Victoria Richon , Richard Rifkind
IPC分类号： A61K31/52 , A61K31/445 , A61K31/426 , A61K31/19 , C07D211/30 , A61K31/44
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。

4. 发明申请

US20070010536A1 Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof 审中-公开
标题翻译：新型细胞分化剂和组蛋白脱乙酰酶抑制剂及其使用方法
公开(公告)号：US20070010536A1
公开(公告)日：2007-01-11
申请号：US11473839
申请日：2006-06-22
申请人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas Miller , Paul Marks , Victoria Richon , Richard Rifkind
发明人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas Miller , Paul Marks , Victoria Richon , Richard Rifkind
IPC分类号： A61K31/52 , A61K31/445 , A61K31/44 , C07C259/04
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。

5. 发明申请

US20060030019A1 HDAC9 polypeptides and polynucleotides and uses thereof 有权
标题翻译： HDAC9多肽及其多核苷酸及其用途
公开(公告)号：US20060030019A1
公开(公告)日：2006-02-09
申请号：US11202268
申请日：2005-08-10
申请人： Victoria Richon , Xianbo Zhou , Richard Rifkind , Paul Marks
发明人： Victoria Richon , Xianbo Zhou , Richard Rifkind , Paul Marks
IPC分类号： C07H21/04 , C12P21/06 , C12N9/16
CPC分类号： C12N9/16 , C12N9/80
摘要： The present invention features substantially pure HDAC9, HDAC9a, HDAC9(ΔNLS), HDAC9a(ΔNLS), an HDRP(ΔNLS) polypeptides, and isolated nucleic acid molecules encoding those polypeptides. The present invention also features vectors containing HDAC9, HDAC9a, HDAC9(ΔNLS), HDAC9a(ΔNLS), and HDRP(ΔNLS) nucleic acid sequences, and cells containing those vectors.
摘要翻译：本发明具有基本上纯的HDAC9，HDAC9a，HDAC9（DeltaNLS），HDAC9a（DeltaNLS），HDRP（DeltaNLS）多肽以及编码这些多肽的分离的核酸分子。本发明还包含含有HDAC9，HDAC9a，HDAC9（DeltaNLS），HDAC9a（DeltaNLS）和HDRP（ΔNLS）核酸序列的载体和含有这些载体的细胞。

6. 发明申请

US20070155785A1 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：US20070155785A1
公开(公告)日：2007-07-05
申请号：US11710036
申请日：2007-02-22
申请人： Ronald Breslow , Thomas Miller , Sandro Belvedere , Paul Marks , Victoria Richon , Richard Rifkind
发明人： Ronald Breslow , Thomas Miller , Sandro Belvedere , Paul Marks , Victoria Richon , Richard Rifkind
IPC分类号： A61K31/4709 , C07D401/02
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

7. 发明申请

US20070087427A1 Crystal structure of a deacetylase and inhibitors thereof 审中-公开
标题翻译：脱乙酰酶的晶体结构及其抑制剂
公开(公告)号：US20070087427A1
公开(公告)日：2007-04-19
申请号：US11505214
申请日：2006-08-16
申请人： Nikola Pavletich , Michael Finnin , Jill Donigian , Victoria Richon , Richard Rifkind , Paul Marks , Ronald Breslow
发明人： Nikola Pavletich , Michael Finnin , Jill Donigian , Victoria Richon , Richard Rifkind , Paul Marks , Ronald Breslow
IPC分类号： C12N9/18 , G06F19/00
CPC分类号： C12N9/16
摘要： The present invention provides three-dimensional structural information from the hyperthermophilic bacterium Aquifex aeolicus which is a histone deacetylase-like protein (HDLP). HDLP shares 35.2% amino acid sequence identity with human histone deacetylase (HDAC1). The present invention further provides three-dimensional structural information of HDLP bound by inhibitor molecules. The three-dimensional structural information of the present invention is useful to design, isolate and screen deacetylase inhibitor compounds capable of inhibiting HDLP, HDAC family members and HDLP-related molecules. The invention also relates to nucleic acids encoding a mutant HDLP which facilitates the determination of the three-dimensional structure of HDLP in the presence of a zinc atom.
摘要翻译：本发明提供来自作为组蛋白脱乙酰酶样蛋白质（HDLP）的超嗜热菌Aquifex aeolicus的三维结构信息。 HDLP与人组蛋白脱乙酰酶（HDAC1）具有35.2％的氨基酸序列同一性。本发明还提供了由抑制剂分子结合的HDLP的三维结构信息。本发明的三维结构信息可用于设计，分离和筛选能够抑制HDLP，HDAC家族成员和HDLP相关分子的脱乙酰酶抑制剂化合物。本发明还涉及编码突变型HDLP的核酸，其有助于在锌原子存在下测定HDLP的三维结构。

8. 发明申请

US20070010669A1 Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof 审中-公开
标题翻译：新型细胞分化剂和组蛋白脱乙酰酶抑制剂及其使用方法
公开(公告)号：US20070010669A1
公开(公告)日：2007-01-11
申请号：US11474042
申请日：2006-06-22
申请人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas Miller , Paul Marks , Victoria Richon , Richard Rifkind
发明人： Ronald Breslow , Sandro Belvedere , Leland Gershell , Thomas Miller , Paul Marks , Victoria Richon , Richard Rifkind
IPC分类号： C07D473/02 , C07D211/06 , C07C259/04 , C07D213/56
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/或凋亡并因此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。

9. 发明申请

US20060079551A1 Treatment of neurodegenerative diseases and cancer of the brain using histone deacetylase inhibitors 有权
标题翻译：使用组蛋白脱乙酰酶抑制剂治疗神经变性疾病和脑癌
公开(公告)号：US20060079551A1
公开(公告)日：2006-04-13
申请号：US11282420
申请日：2005-11-18
申请人： Victoria Richon , Paul Marks , Richard Rifkind
发明人： Victoria Richon , Paul Marks , Richard Rifkind
IPC分类号： A61K31/47 , A61K31/44 , A61K31/381 , A61K31/325 , A61K31/19
CPC分类号： A61K31/16 , A61K31/00 , A61K31/166 , A61K31/167 , A61K31/19 , A61K31/4406 , A61K31/47 , A61K31/4709
摘要： The present application is directed to a method of treating diseases of the central nervous system (CNS) comprising administering to a individual in need of treatment a therapeutically effective amount of an inhibitor of histone deacetylase. In particular embodiments, the CNS disease is a neurodegenerative disease. In further embodiments, the neurogenerative disease is an inherited neurodegenerative disease, such as those inherited neurodegenerative diseases which are polyglutamine expansion diseases. The individual can be a mammal such as a primate or human.
摘要翻译：本申请涉及治疗中枢神经系统疾病（CNS）的方法，包括向需要治疗的个体施用治疗有效量的组蛋白脱乙酰酶抑制剂。在具体实施方案中，CNS疾病是神经变性疾病。在进一步的实施方案中，神经生殖疾病是遗传性神经变性疾病，例如遗传性神经变性疾病，其是多谷氨酰胺扩张疾病。个体可以是哺乳动物，如灵长类动物或人类。

10. 发明申请

US20070190022A1 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：US20070190022A1
公开(公告)日：2007-08-16
申请号：US10567953
申请日：2004-08-12
申请人： Nicholas Bacopoulos , Judy Chiao , Paul Marks , Thomas Miller , Carolyn Paradise , Victoria Richon , Richard Rifkind
发明人： Nicholas Bacopoulos , Judy Chiao , Paul Marks , Thomas Miller , Carolyn Paradise , Victoria Richon , Richard Rifkind
IPC分类号： A61K38/20 , A61K38/19 , A61K38/09 , A61K31/7072 , A61K31/57 , A61K31/522 , A61K31/19
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。

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