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。

公开(公告)号：US07652069B2

公开(公告)日：2010-01-26

申请号：US11981367

申请日：2007-10-30

申请人： Thomas A. Miller ,  Victoria M. Richon

发明人： Thomas A. Miller ,  Victoria M. Richon

IPC分类号： A61A31/16 ,  C07C259/04

CPC分类号： A61K31/19 ,  A61K9/0019 ,  A61K9/1652 ,  A61K9/4866 ,  A61K31/13 ,  A61K31/165 ,  A61K31/44 ,  A61K47/12 ,  A61K47/38 ,  C07B2200/13 ,  C07C259/06

摘要： The present invention provides methods of 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. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.

公开(公告)号：US20090270351A1

公开(公告)日：2009-10-29

申请号：US12309459

申请日：2007-07-16

申请人： Joshua Close ,  Jonathan Grimm ,  Richard W. Heidebrecht, JR. ,  Solomon Kattar ,  Thomas A. Miller ,  Karin M. Otte ,  Scott Peterson ,  Phieng Siliphaivanh ,  Paul J. Tempest ,  Kevin J. Wilson ,  David J. Witter

发明人： Joshua Close ,  Jonathan Grimm ,  Richard W. Heidebrecht, JR. ,  Solomon Kattar ,  Thomas A. Miller ,  Karin M. Otte ,  Scott Peterson ,  Phieng Siliphaivanh ,  Paul J. Tempest ,  Kevin J. Wilson ,  David J. Witter

IPC分类号： A61K31/675 ,  A61K31/67 ,  C07F9/28 ,  C07D333/04

CPC分类号： C07F9/655345 ,  C07F9/5304 ,  C07F9/5325 ,  C07F9/65031 ,  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.

摘要翻译： 本发明涉及一类新型的磷衍生物。 磷化合物可用于治疗癌症。 磷化合物也可以抑制组蛋白脱乙酰酶，适用于选择性诱导末端分化，阻止肿瘤细胞的细胞生长和/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疾病（CNS），例如 神经退行性疾病 本发明进一步提供包含磷衍生物和这些药物组合物的安全给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磷衍生物。

公开(公告)号：US20090082308A1

公开(公告)日：2009-03-26

申请号：US11918913

申请日：2006-04-14

申请人： Jed Lee Hubbs ,  Dawn M. Mampreian ,  Joey L. Methot ,  Thomas A. Miller ,  Karin M. Otte ,  Phieng Siliphaivanh ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin J. Wilson ,  David J. Witter

发明人： Jed Lee Hubbs ,  Dawn M. Mampreian ,  Joey L. Methot ,  Thomas A. Miller ,  Karin M. Otte ,  Phieng Siliphaivanh ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin J. Wilson ,  David J. Witter

IPC分类号： A61K31/695 ,  C07D333/56 ,  A61K31/381 ,  C07D409/12 ,  A61K31/4709 ,  C07D409/10 ,  A61K31/4025 ,  C07D409/06 ,  A61K31/496 ,  C07D413/12 ,  A61P25/00 ,  A61P35/00 ,  A61K31/4155 ,  A61K31/506 ,  C07F7/08 ,  A61K31/5377 ,  C07D409/14 ,  A61K31/4178 ,  A61K31/404 ,  A61K31/4436 ,  A61K31/4245 ,  A61K31/4192

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.

摘要翻译： 本发明涉及一类新型的苯并噻吩酰胺衍生物。 异羟肟酸化合物可用于治疗癌症。 苯并噻吩酰胺化合物也可以抑制组蛋白脱乙酰酶，适用于选择性诱导末端分化，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疾病（CNS），例如 神经退行性疾病 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，它们易于遵循，并且其在体内导致治疗有效量的异羟肟酸衍生物。

公开(公告)号：US20080132575A1

公开(公告)日：2008-06-05

申请号：US11663165

申请日：2006-05-16

申请人： Jeannie Chow Wong ,  Aaron S. Cote ,  Erik A. Dienemann ,  Kimberly Gallagher ,  Craig Ikeda ,  Justin Moser ,  Pavol Rajniak ,  Robert A. Reed ,  Cindy Starbuck ,  Hsien-Hsin Tung ,  Qingxi Wang ,  Benjamin Max Cohen ,  Vincent R. Capodanno ,  Brian Sell ,  Thomas A. Miller

发明人： Jeannie Chow Wong ,  Aaron S. Cote ,  Erik A. Dienemann ,  Kimberly Gallagher ,  Craig Ikeda ,  Justin Moser ,  Pavol Rajniak ,  Robert A. Reed ,  Cindy Starbuck ,  Hsien-Hsin Tung ,  Qingxi Wang ,  Benjamin Max Cohen ,  Vincent R. Capodanno ,  Brian Sell ,  Thomas A. Miller

IPC分类号： A61K31/185 ,  A61P35/00

CPC分类号： A61K31/19

摘要： The present invention provides a pharmaceutical composition or crystalline composition with a specific dissolution profile, which comprises suberoylanilide hydroxamic acid or a pharmaceutically acceptable salt or hydrate thereof as an active ingredient. The present invention provides a process of producing said crystalline composition or pharmaceutical composition. The present invention also provides compositions with a specific particle size distribution.

摘要翻译： 本发明提供具有特定溶出曲线的药物组合物或结晶组合物，其包含辛二酰苯胺异羟肟酸或其药学上可接受的盐或水合物作为活性成分。 本发明提供了制备所述结晶组合物或药物组合物的方法。 本发明还提供具有特定粒度分布的组合物。

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.

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）。

公开(公告)号：US5865232A

公开(公告)日：1999-02-02

申请号：US813669

申请日：1997-03-07

申请人： Thomas A. Miller ,  Darrel C. Pinkston

发明人： Thomas A. Miller ,  Darrel C. Pinkston

IPC分类号： B25B5/00 ,  B25B5/08 ,  B25B5/14 ,  B27L5/00 ,  B27L5/04 ,  B27L5/06 ,  B27C1/00 ,  B27M1/02

CPC分类号： B27L5/04 ,  B25B5/003 ,  B25B5/087 ,  B25B5/147 ,  B27L5/004 ,  B27L5/06

摘要： A novel method and apparatus for cutting veneer sheets from a tapered flitch (one-half of a veneer log which has been sawn in half longitudinally) that places the veneer producing face of a tapered flitch in a stable, parallel relationship with the veneer slicing knife, thereby allowing full utilization of the natural taper of a veneer log.

摘要翻译： 一种新颖的方法和装置，用于从锥形薄片（已经锯切成两半纵向的薄板原木的一半）切割单板，其将单板生产锥形薄片的表面与单板切片刀保持稳定的平行关系 ，从而允许充分利用单板日志的天然锥度。

公开(公告)号：US5747057A

公开(公告)日：1998-05-05

申请号：US626001

申请日：1996-04-01

申请人： Thomas A. Miller

发明人： Thomas A. Miller

IPC分类号： A01K13/00 ,  A01K27/00 ,  A01N37/52 ,  A01N43/40 ,  A01N47/12 ,  A01N53/02 ,  A61K9/00 ,  A01N25/34 ,  A01N31/44

CPC分类号： A01N43/40

摘要： The invention comprises a composition of matter containing a matrix, a plasticizer and pyriproxifen for controlling fleas.

摘要翻译： 本发明包括含有基质的物质组合物，增塑剂和用于控制跳蚤的吡哆酮。

公开(公告)号：US5632999A

公开(公告)日：1997-05-27

申请号：US108909

申请日：1993-08-18

申请人： Thomas A. Miller

发明人： Thomas A. Miller

IPC分类号： A01K13/00 ,  A01K27/00 ,  A01N37/52 ,  A01N43/40 ,  A01N47/12 ,  A01N53/02 ,  A61K9/00 ,  A01N25/34

CPC分类号： A01N43/40

摘要： The invention comprises a method of controlling fleas which includes continuously administering to the haircoat of a homeothermic animal an ovicidally effective amount of 2-(1-methyl-2-(4-phenoxyphenoxy)ethoxy)pyridine (pyriproxifen) from a sustained release matrix at a rate of 0.1 mcg/kg/day to 100 mcg/kg/day. The method may also include the use of additional ingredients such as insecticides, plasticizers, lubricants and antioxidants in a sustained release matrix.

摘要翻译： 本发明包括一种控制跳蚤的方法，其包括向持续释放基质中的持续释放基质中持续施用有效量的2-（1-甲基-2-（4-苯氧基苯氧基）乙氧基）吡啶（吡氯西泮） 速率为0.1mcg / kg /天至100mcg / kg /天。 该方法还可以包括在持续释放基质中使用附加成分例如杀虫剂，增塑剂，润滑剂和抗氧化剂。