公开(公告)号：US20150024040A1

公开(公告)日：2015-01-22

申请号：US14510369

申请日：2014-10-09

Applicant: LES LABORATORIES SERVIER ,  PHARMACYCLICS, INC.

Inventor： Ioana Kloos ,  Renata Robert ,  Anne Jacquet-Bescond ,  Stéphane Depil ,  Marylore Chenel ,  Sylvain Fouliard ,  Sriram Balasubramanian

IPC: A61K31/343 ,  A61N5/10 ,  A61K31/138 ,  A61K33/24 ,  A61K31/704

CPC classification number: A61K31/343 ,  A61K31/138 ,  A61K31/704 ,  A61K33/24 ,  A61N5/10 ,  A61K2300/00

Abstract: N-hydroxy-4-{2-[3-(N,N-dimethylaminomethyl)benzofuran-2-ylcarbonylamino]ethoxy}-benzamide of formula (I): or an addition salt thereof with a pharmaceutically acceptable acid or base, alone or in association with surgery, chemotherapy or hormone therapy treatment or radiotherapy, for use in the treatment of cancer, characterised in that it is administered for 4 consecutive days, that period being followed by 3 consecutive days without any administration of compound of formula (I), with the proviso that the chemotherapy is not FOLFOX.

Abstract translation: 式（I）的N-羟基-4- {2- [3-（N，N-二甲基氨基甲基）苯并呋喃-2-基羰基氨基]乙氧基} - 苯甲酰胺或其药学上可接受的酸或碱的加成盐，单独或 与用于治疗癌症的手术，化学疗法或激素疗法治疗或放射疗法联合使用，其特征在于其连续连续服用4天，随后连续3天，而不施用式（I）化合物， ，但条件是化疗不是FOLFOX。

公开(公告)号：US08900565B2

公开(公告)日：2014-12-02

申请号：US13683880

申请日：2012-11-21

Applicant: Pharmacyclics, Inc.

Inventor： Joseph J. Buggy ,  Sriram Balasubramanian ,  Erik Verner ,  Vincent W. F. Tai ,  Chang-Sun Lee

IPC: A61K31/405 ,  A61K31/55 ,  A61K45/06 ,  C07D209/08 ,  C07D209/42 ,  A61K31/5377 ,  C07D209/12 ,  A61K31/404 ,  C07D209/14

CPC classification number: C07D209/08 ,  A61K31/404 ,  A61K31/5377 ,  A61K45/06 ,  C07D209/12 ,  C07D209/14 ,  C07D209/42 ,  C07D403/06 ,  A61K2300/00 ,  A61K31/55

Abstract: Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

Abstract translation: 本文描述了含有这种化合物的化合物和药物组合物，其抑制组蛋白脱乙酰酶8（HDAC8）的活性。 本文还描述了将这样的HDAC8抑制剂单独使用并与其它化合物联合用于治疗将受益于抑制HDAC8活性的疾病或病症的方法。

公开(公告)号：US20140336206A1

公开(公告)日：2014-11-13

申请号：US14340483

申请日：2014-07-24

Applicant: PHARMACYCLICS, INC.

Inventor： Lee HONIGBERG ,  Erik VERNER ,  Zhengying PAN

IPC: C07D487/04

CPC classification number: A61K31/52 ,  A61K9/4825 ,  A61K31/00 ,  A61K31/519 ,  A61K39/3955 ,  A61K45/06 ,  A61K2300/00 ,  C07D487/04 ,  C07K16/2887 ,  C07K2317/24

Abstract: Disclosed herein are pyrazolo[3,4-d]pyrimidines that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract translation: 本文公开了与布鲁特酪氨酸激酶（Btk）形成共价键的吡唑并[3,4-d]嘧啶。 还描述了Btk的不可逆抑制剂。 公开了制备化合物的方法。 还公开了包含化合物的药物组合物。 公开了使用Btk抑制剂的方法，单独或与其它治疗剂组合用于治疗自身免疫性疾病或病症，异种免疫疾病或病症，癌症，包括淋巴瘤和炎性疾病或病症。

公开(公告)号：US20140336203A1

公开(公告)日：2014-11-13

申请号：US14339363

申请日：2014-07-23

Applicant: Pharmacyclics, Inc.

Inventor： Mark SMYTH ,  Erick GOLDMAN ,  David D. WIRTH ,  Norbert PURRO

IPC: C07D487/04

CPC classification number: C07D487/04 ,  A61J1/035 ,  A61K9/0053 ,  A61K9/2013 ,  A61K9/2018 ,  A61K9/2054 ,  A61K9/4825 ,  A61K9/4858 ,  A61K9/4866 ,  A61K31/519 ,  A61K45/06 ,  B65D75/36 ,  C07B2200/13 ,  A61K2300/00

Abstract: Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract translation: 本文描述了Bruton的酪氨酸激酶（Btk）抑制剂1 - （（R）-3-（4-氨基-3-（4-苯氧基苯基）-1H-吡唑并[3,4-d]嘧啶-1-基）哌啶 -1-基）丙-2-烯-1-酮，包括结晶形式，溶剂化物和药学上可接受的盐。 还公开了包括Btk抑制剂的药物组合物，以及使用Btk抑制剂单独或与其它治疗剂组合用于治疗自身免疫疾病或病症，异种免疫疾病或病症，癌症（包括淋巴瘤）和 炎性疾病或病症。

公开(公告)号：US20140128414A1

公开(公告)日：2014-05-08

申请号：US14033344

申请日：2013-09-20

Applicant: Pharmacyclics, Inc.

Inventor： Lee Honigberg ,  Erik Verner ,  Zhengying Pan

IPC: C07D487/04

CPC classification number: A61K31/52 ,  A61K9/4825 ,  A61K31/00 ,  A61K31/519 ,  A61K39/3955 ,  A61K45/06 ,  A61K2300/00 ,  C07D487/04 ,  C07K16/2887 ,  C07K2317/24

Abstract: Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract translation: 本文公开了与布鲁顿酪氨酸激酶（Btk）形成共价键的化合物。 还描述了Btk的不可逆抑制剂。 公开了制备化合物的方法。 还公开了包含化合物的药物组合物。 公开了使用Btk抑制剂的方法，单独或与其它治疗剂组合用于治疗自身免疫性疾病或病症，异种免疫疾病或病症，癌症，包括淋巴瘤和炎性疾病或病症。

公开(公告)号：US20130156727A1

公开(公告)日：2013-06-20

申请号：US13683880

申请日：2012-11-21

Applicant: Pharmacyclics, Inc.

Inventor： Joseph J. BUGGY ,  Sriram Balasubramanian ,  Erik Verner ,  Vincent W.F. Tai ,  Chang-Sun Lee

IPC: A61K45/06 ,  A61K31/404 ,  A61K31/5377 ,  C07D209/42

CPC classification number: C07D209/08 ,  A61K31/404 ,  A61K31/5377 ,  A61K45/06 ,  C07D209/12 ,  C07D209/14 ,  C07D209/42 ,  C07D403/06 ,  A61K2300/00 ,  A61K31/55

Abstract: Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

公开(公告)号：US20130078215A1

公开(公告)日：2013-03-28

申请号：US13668170

申请日：2012-11-02

Applicant: PHARMACYCLICS, INC.

Inventor： Joseph J. Buggy ,  Sriram Balasubramanian ,  Susanne M. Steggerda

IPC: C07D209/10 ,  C07D403/06 ,  C07D209/08 ,  C07D209/12 ,  A61K45/06 ,  A61K31/405 ,  A61K31/454 ,  A61K31/5377 ,  A61K31/4245 ,  C07D401/06 ,  C07D413/06

CPC classification number: C07D209/12 ,  A61K31/404 ,  A61K31/4045 ,  A61K31/405 ,  A61K31/4245 ,  A61K31/454 ,  A61K31/5377 ,  A61K45/06 ,  C07D209/08 ,  C07D209/10 ,  C07D401/06 ,  C07D403/06 ,  C07D413/06

Abstract: Described herein are methods for treating a subject suffering from an inflammatory, autoimmune, or heteroimmune condition by administering to the subject a pharmaceutical composition containing a therapeutically effective amount of a compound that is a selective inhibitor of histone deacetylase 8. Also described herein are methods for decreasing secretion of pro-inflammatory cytokines by administering an HDAC8-selective inhibitor compound. Further described herein are methods for predicting responsiveness to treatments for inflammatory conditions. Methods for predicting efficacy of treatments for inflammatory conditions are also described.

Abstract translation: 本文描述了通过向受试者施用含有治疗有效量的作为组蛋白脱乙酰酶8的选择性抑制剂的化合物的药物组合物来治疗患有炎症，自身免疫或异种免疫病症的受试者的方法。本文还描述了用于 通过施用HDAC8选择性抑制剂化合物来减少促炎细胞因子的分泌。 本文进一步描述了用于预测对治疗炎症反应的方法。 还描述了用于预测炎症病症治疗功效的方法。

公开(公告)号：WO2015127261A1

公开(公告)日：2015-08-27

申请号：PCT/US2015/016895

申请日：2015-02-20

Applicant: PHARMACYCLICS, INC.

Inventor： BURGER, Jan, A.

IPC: A61K31/519

CPC classification number: A61K31/519 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/57426 ,  G01N2333/523 ,  G01N2800/52

Abstract: Described herein are diagnostic methods for selecting patients diagnosed with diffuse large B-cell lymphoma (DLBCL) for treatment with an inhibitor of Bruton's tyrosine kinase (BTK) based on the level of expression the biomarkers CCL3 and/or CCL4. Also provided are methods for identifying DLBCL patients likely to respond to treatment with a BTK inhibitor and for evaluating treatment of DLBCL with a BTK inhibitor. Methods of treating a patient also are provided. Also provided are compositions, combinations, and kits.

Abstract translation: 本文描述了基于生物标志物CCL3和/或CCL4的表达水平，选择诊断为弥漫性大B细胞淋巴瘤（DLBCL）的患者用于用Bruton酪氨酸激酶（BTK）抑制剂治疗的诊断方法。 还提供了用于鉴定可能用BTK抑制剂治疗反应的DLBCL患者和用BTK抑制剂评价DLBCL治疗的方法。 还提供了治疗患者的方法。 还提供了组合物，组合和试剂盒。

公开(公告)号：WO2015061751A1

公开(公告)日：2015-04-30

申请号：PCT/US2014/062277

申请日：2014-10-24

Applicant: PHARMACYCLICS, INC. ,  BYRD, John, C. ,  DUBOVSKY, Jason, A. ,  MUTHUSAMY, Natarajan ,  JOHNSON, Amy, Jo

Inventor： BYRD, John, C. ,  DUBOVSKY, Jason, A. ,  MUTHUSAMY, Natarajan ,  JOHNSON, Amy, Jo ,  MIKLOS, David

IPC: A61K31/519 ,  A61K31/505 ,  A61P37/00

CPC classification number: A61K31/519 ,  A61K31/5377 ,  A61K31/56 ,  A61K35/17 ,  A61K35/28 ,  A61K38/13 ,  A61K45/06 ,  A61K2300/00

Abstract: Described herein are methods for treating and preventing graft versus host disease using ACK inhibitors. The methods include administering to an individual in need thereof an ACK inhibitor such as ibrutinib for treating and preventing graft versus host disease.

Abstract translation: 本文描述了使用ACK抑制剂治疗和预防移植物抗宿主病的方法。 所述方法包括向有需要的个体施用ACK抑制剂如伊布他坦，用于治疗和预防移植物抗宿主病。

公开(公告)号：WO2015048689A1

公开(公告)日：2015-04-02

申请号：PCT/US2014/058132

申请日：2014-09-29

Applicant: PHARMACYCLICS, INC.

Inventor： WANG, Longcheng ,  CHEN, Wei ,  JIA, Zhaozahong, J. ,  LOURY, David, J.

IPC: C07D403/14 ,  C07D401/14 ,  A61K31/519 ,  A61P19/02 ,  A61P19/00

CPC classification number: C07D487/04

Abstract: Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Abstract translation: 本文所公开的是与布鲁顿酪氨酸激酶（Btk）形成共价键的化合物。 还描述了Btk的不可逆抑制剂。 另外，还描述了Btk的可逆抑制剂。 还公开了包含该化合物的药物组合物。 单独或与其他治疗剂组合使用Btk抑制剂的方法用于治疗自身免疫性疾病或病症，异质性免疫疾病或病症，癌症（包括淋巴瘤和炎性疾病或病症）。