公开(公告)号：WO9746262A2

公开(公告)日：1997-12-11

申请号：PCT/US9709501

申请日：1997-06-04

Applicant: PHARMACYCLICS INC ,  UNIV TEXAS ,  YOUNG STUART W ,  WRIGHT MEREDITH ,  SESSLER JONATHAN L ,  MODY TARAK D ,  MAGDA DARREN

Inventor： YOUNG STUART W ,  WRIGHT MEREDITH ,  SESSLER JONATHAN L ,  MODY TARAK D ,  MAGDA DARREN

IPC: C07D487/22 ,  A61K9/127 ,  A61K9/50 ,  A61K31/40 ,  A61K31/409 ,  A61K35/18 ,  A61K41/00 ,  A61K47/48 ,  A61K49/00

CPC classification number: A61K49/1896 ,  A61K9/127 ,  A61K9/1271 ,  A61K9/5068 ,  A61K41/0076 ,  A61K47/554 ,  A61K47/6901 ,  A61K47/6911 ,  A61K49/085

Abstract: Compositions having a texaphyrin-lipophilic molecule conjugate loaded into a biological vesicle and methods for imaging, diagnosis and treatment using the loaded vesicle are provided. For example, liposomes or red blood cells loaded with a paramagnetic texaphyrin-lipophilic molecule conjugate have utility as a blood pool contrast agent, facilitating the enhancement of normal tissues, magnetic resonance angiography, and marking areas of damaged endothelium by their egress through fenestrations or damaged portions of the blood vascular system. Liposomes or cells loaded with a photosensitive texaphyrin-lipophilic molecule conjugate can be photolysed, allowing for a photodynamic therapy effect at the site of lysis. Availability of red blood cells loaded with a photosensitive texaphyrin-lipophilic molecule conjugate provides a method for delivering a photodynamic therapeutic agent to a desired site with a high concentration of oxygen. By presenting the agent in this way, it is expected that a patient will experience less toxicity.

Abstract translation: 提供了具有加载到生物囊泡中的泰克萨菲瑞 - 亲脂性分子缀合物的组合物以及使用加载的囊泡进行成像，诊断和治疗的方法。 例如，装载有顺磁性泰克萨菲瑞 - 亲脂性分子缀合物的脂质体或红细胞具有作为血液池造影剂的效用，有助于正常组织的增强，磁共振血管造影术，以及通过开窗口或损伤的出口来损伤内皮的标记区域 部分血管系统。 可以光密化具有感光性泰克萨菲瑞 - 亲脂性分子缀合物的脂质体或细胞，从而在裂解部位产生光动力学治疗效果。 载有感光性泰克萨菲瑞 - 亲脂性分子缀合物的红细胞的可获得性提供了一种将光动力治疗剂递送至具有高浓度氧的所需部位的方法。 通过以这种方式呈现代理，预期患者的毒性将较低。

公开(公告)号：WO1995010307A1

公开(公告)日：1995-04-20

申请号：PCT/US1994011491

申请日：1994-10-12

Applicant: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM ,  PHARMACYCLICS, INC. ,  SESSLER, Jonathan, L. ,  HARRIMAN, Anthony, M. ,  MILLER, Richard, A. ,  MODY, Tarak, D. ,  HEMMI, Gregory, W. ,  KRÅL, Vladimir, A. ,  MAGDA, Darren

Inventor： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM ,  PHARMACYCLICS, INC.

IPC: A61K51/04

CPC classification number: A61K51/0485 ,  A61K41/0038 ,  A61K41/0057 ,  A61K41/0076 ,  A61K47/546 ,  A61K49/0021 ,  A61K49/0054 ,  A61K49/085 ,  A61K49/10 ,  A61K49/106 ,  A61K49/126 ,  A61L2/0011 ,  B01J31/061 ,  B01J31/1658 ,  B01J31/1805 ,  B01J31/1815 ,  B01J2531/025 ,  B01J2531/23 ,  B01J2531/26 ,  B01J2531/27 ,  B01J2531/28 ,  B01J2531/36 ,  B01J2531/37 ,  B01J2531/38 ,  B01J2531/72 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  B01J2531/96 ,  C07D487/22 ,  C07H21/00

Abstract: Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

Abstract translation: 特拉法芬被提供用作辐射敏化剂。 泰克萨菲瑞用作辐射敏化剂的有利特性包括：i）低的氧化还原电位，其允许辐射诱导的水合电子流向泰克萨菲瑞而不是中和羟基，允许羟基自由基引起细胞损伤，ii）相对稳定的泰克萨菲瑞基 其易于共价修饰相邻的分子，导致进一步的细胞损伤，iii）内在的生物定位，以及iv）不存在或不存在O 2。 这些性质使得泰克萨菲瑞对于治疗实体性赘生物的缺氧区域特别有效。 具有肿瘤或动脉粥样硬化的个体的治疗方法包括使用泰克萨菲林作为辐射敏化剂和作为光动力学肿瘤治疗的药剂，或者使用泰克萨菲瑞用于内部和外部电离辐射。 提供了新的泰克萨菲标本。

公开(公告)号：WO2015084998A1

公开(公告)日：2015-06-11

申请号：PCT/US2014/068434

申请日：2014-12-03

Applicant: PHARMACYCLICS, INC.

Inventor： JIA, Zhaozhong, J. ,  THOMAS, William, D. ,  CHEN, Wei

IPC: C07D403/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D401/04 ,  C07D401/12 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  A61K31/497 ,  A61K31/53 ,  A61P19/00 ,  A61P35/00 ,  A61P37/00

CPC classification number: C07D401/04 ,  A61K31/397 ,  A61K31/4025 ,  A61K31/445 ,  A61K31/497 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: Disclosed herein are reversible and irreversible inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are described, 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Bruton酪氨酸激酶（Btk）的可逆和不可逆抑制剂。 还公开了包含化合物的药物组合物。 描述了使用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的方法。

公开(公告)号：WO2015048689A8

公开(公告)日：2015-05-07

申请号：PCT/US2014058132

申请日：2014-09-29

Applicant: PHARMACYCLICS INC

Inventor： WANG LONGCHENG ,  CHEN WEI ,  JIA ZHAOZHONG J ,  LOURY DAVID J

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

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。 此外，还描述了Btk的可逆抑制剂。 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：WO2015061752A1

公开(公告)日：2015-04-30

申请号：PCT/US2014/062278

申请日：2014-10-24

Applicant: PHARMACYCLICS, INC. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

Inventor： LEVY, Ronald ,  CHANG, Betty ,  NG, Patrick ,  SAGIV-BARFI, Idit

IPC: A61K39/395 ,  A61K31/519 ,  A61P35/00

CPC classification number: A61K39/3955 ,  A61K31/519 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/2818 ,  C07K16/2827 ,  Y02A50/463 ,  A61K2300/00

Abstract: Combinations of Bruton's tyrosine kinase (Btk) inhibitors, e.g., l-((R)-3-(4-amino-3-(4- phenoxyphenyl)- 1 H-pyrazolo [3,4-d]pyrimidin- 1 -yl)piperidin- 1 -yl)prop-2-en- 1 -one, with immunotherapy are provided. Also provided are methods of treating cancers, and autoimmune disorders by administering combinations of Bruton's tyrosine kinase (Btk) inhibitors, e.g., 1- ((R)-3-(4-amino-3-(4-phenoxyphenyl)-lH-pyrazolo[3,4-d]pyrimidin-l-yl)piperidin-l-yl)prop-2- en-l-one, and an immune checkpoint inhibitor.

Abstract translation: Bruton酪氨酸激酶（Btk）抑制剂的组合，例如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，并进行免疫疗法。 还提供了通过施用布鲁顿酪氨酸激酶（Btk）抑制剂，例如，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-酮和免疫检查点抑制剂。

公开(公告)号：WO2014078578A1

公开(公告)日：2014-05-22

申请号：PCT/US2013/070164

申请日：2013-11-14

Applicant: PHARMACYCLICS, INC.

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

IPC: C07D487/04 ,  A61K31/519 ,  A61P37/00 ,  A61P35/00 ,  A61P29/00

CPC classification number: C07D487/04 ,  A61K31/519

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。 此外，还描述了Btk的可逆抑制剂。 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：WO2013184572A1

公开(公告)日：2013-12-12

申请号：PCT/US2013/043888

申请日：2013-06-03

Applicant: PHARMACYCLICS, INC. ,  PURRO, Norbert

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

IPC: A61K47/38 ,  A61K47/30 ,  A61K9/48 ,  A61P35/00 ,  A61P29/00

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：WO2013123413A2

公开(公告)日：2013-08-22

申请号：PCT/US2013/026462

申请日：2013-02-15

Applicant: PHARMACYCLICS, INC.

Inventor： BALASUBRAMANIAN, Sriram ,  MODY, Tarak, D.

IPC: A61K31/506 ,  A61K31/517 ,  A61P35/00

CPC classification number: A61K31/343 ,  A61K31/506 ,  A61K45/06 ,  A61N5/10 ,  A61K2300/00

公开(公告)号：WO2013116382A1

公开(公告)日：2013-08-08

申请号：PCT/US2013/023918

申请日：2013-01-30

Applicant: PHARMACYCLICS, INC. ,  YAN, Shunqi ,  WANG, Longcheng ,  FRYE, Leah, Lynn

Inventor： YAN, Shunqi ,  WANG, Longcheng ,  FRYE, Leah, Lynn ,  CHEN, Wei ,  LOURY, David, J.

IPC: C07D473/32 ,  A61K31/52 ,  A61P37/00 ,  A61P35/00

CPC classification number: C07D473/34

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。 此外，还描述了Btk的可逆抑制剂。 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：WO2013102059A1

公开(公告)日：2013-07-04

申请号：PCT/US2012/072043

申请日：2012-12-28

Applicant: PHARMACYCLICS, INC.

Inventor： CHEN, Wei ,  LOURY, David, J.

IPC: C07D487/04 ,  C07D403/04 ,  A61K31/519 ,  A61P37/00 ,  A61P35/00

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. 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。