公开(公告)号：US09212185B2

公开(公告)日：2015-12-15

申请号：US14080649

申请日：2013-11-14

Applicant: Pharmacyclics, Inc.

Inventor： Lee Honigberg ,  Erik Verner ,  Zhengying Pan

IPC: A01N43/90 ,  A61K31/519 ,  C07D487/04 ,  A61K31/00 ,  A61K45/06 ,  A61K9/48

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 of Formula (D) 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）形成共价键的式（D）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：US20140243355A1

公开(公告)日：2014-08-28

申请号：US14079508

申请日：2013-11-13

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.

公开(公告)号：US20140187565A1

公开(公告)日：2014-07-03

申请号：US14080649

申请日：2013-11-14

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.

公开(公告)号：US08759516B2

公开(公告)日：2014-06-24

申请号：US13952531

申请日：2013-07-26

Applicant: Pharmacyclics, Inc.

Inventor： Lee Honigberg ,  Erik Verner ,  Zhengying Pan

IPC: C07D487/00

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.

公开(公告)号：US20130225812A1

公开(公告)日：2013-08-29

申请号：US13856380

申请日：2013-04-03

Applicant: Pharmacyclics, Inc.

Inventor： Zhengying Pan ,  Shyr Jiann Li ,  Heleen Scheerens ,  Lee Honigberg ,  Erik Verner

IPC: C07D487/04

CPC classification number: C07D487/04 ,  G01N33/573 ,  G01N2333/9121 ,  G01N2500/00

Abstract: Described herein are probes for Bruton's tyrosine kinase (Btk). Such probes are used to characterize and develop Btk-selective inhibitors intended for therapeutic use.

Abstract translation: 本文描述的是布鲁顿酪氨酸激酶（Btk）的探针。 这种探针用于表征和开发用于治疗用途的Btk选择性抑制剂。

公开(公告)号：US09193735B2

公开(公告)日：2015-11-24

申请号：US14156247

申请日：2014-01-15

Applicant: Pharmacyclics, Inc.

Inventor： Lee Honigberg ,  Erik Verner ,  Zhengying Pan

IPC: A01N43/90 ,  A61K31/519 ,  C07D487/04 ,  A61K31/00 ,  A61K45/06 ,  A61K9/48

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 is a solid oral formulation comprising a therapeutically effective amount of a compound of Formula (A) formulated for release of the compound in the intestine, wherein the compound of Formula (A) has the structure:

Abstract translation: 本文公开了一种固体口服制剂，其包含治疗有效量的配制用于在肠中释放化合物的式（A）化合物，其中式（A）化合物具有以下结构：

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：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：US09181263B2

公开(公告)日：2015-11-10

申请号：US14605854

申请日：2015-01-26

Applicant: PHARMACYCLICS, INC.

Inventor： Lee Honigberg ,  Erik Verner ,  Joseph J. Buggy ,  David Loury ,  Wei Chen

IPC: C07D211/70 ,  C07D211/82 ,  C07D487/04 ,  A61K31/4985 ,  A61K31/519

CPC classification number: C07D487/04 ,  A61K31/4985 ,  A61K31/519 ,  A61K45/06

Abstract: Described herein are irreversible kinase inhibitor compounds, exemplified by compounds of the following structure: methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of a disease such as cancer.

Abstract translation: 本文描述的是不可逆激酶抑制剂化合物，其例子包括以下结构的化合物：用于合成这种不可逆抑制剂的方法，以及使用这种不可逆抑制剂治疗诸如癌症的疾病的方法。