公开(公告)号：WO0132211A2

公开(公告)日：2001-05-10

申请号：PCT/US0029524

申请日：2000-10-27

Applicant: PHARMACYCLICS INC ,  UNIV TEXAS ,  SESSLER JONATHAN L ,  MADGA DARREN

Inventor： SESSLER JONATHAN L ,  MADGA DARREN

IPC: A61K41/00

CPC classification number: A61K41/0038 ,  A61K41/0057 ,  A61K41/0071 ,  A61K41/0076

Abstract: Disclosed are compounds which are conjugates of (a) a moiety capable of localizing in the cells of a tumor or atheroma and (b) a moiety capable of catalyzing the production of reactive oxygen species from a cellular metabolite. The disclosed compounds which are useful for treating atheroma, tumors and other neoplastic tissue.

Abstract translation: 公开了以下化合物：（a）能够在肿瘤或动脉粥样化细胞中定位的部分和（b）能够催化细胞代谢产物产生活性氧的部分的结合物。 所公开的可用于治疗动脉粥样硬化，肿瘤和其它肿瘤组织的化合物。

公开(公告)号：WO1998007733A1

公开(公告)日：1998-02-26

申请号：PCT/US1997014682

申请日：1997-08-20

Applicant: PHARMACYCLICS, INC. ,  MAGDA, Darren ,  CROFTS, Shaun, P. ,  WRIGHT, Meredith

Inventor： PHARMACYCLICS, INC.

IPC: C07H21/00

CPC classification number: C12N15/113 ,  C07H21/00 ,  C12N2310/321 ,  C12N2310/3511 ,  C12Q1/6816 ,  C12N2310/3527

Abstract: Texaphyrin metal complex-oligonucleotide and -oligonucleotide analog conjugates are provided where the texaphyrin is bound to an internal linkage of the oligonucleotide or oligonucleotide analog, the conjugates having catalytic activity for the hydrolysis of ribonucleic acid. Further, conjugates demonstrating catalytic turnover are described, the conjugates being especially effective under conditions where the concentration of RNA target exceeds that of available conjugate.

Abstract translation: 提供了Texaphyrin金属络合物 - 寡核苷酸和寡核苷酸类似物缀合物，其中泰克萨菲瑞与寡核苷酸或寡核苷酸类似物的内部连接键合，该缀合物具有核糖核酸水解的催化活性。 此外，描述了显示催化周转的结合物，缀合物在RNA靶标的浓度超过可用缀合物浓度的条件下特别有效。

公开(公告)号：WO1997026915A1

公开(公告)日：1997-07-31

申请号：PCT/US1997000907

申请日：1997-01-23

Applicant: PHARMACYCLICS, INC. ,  MILLER, Richard, A. ,  YOUNG, Stuart, W.

Inventor： PHARMACYCLICS, INC.

IPC: A61K41/00

CPC classification number: A61K31/555 ,  A61K31/675 ,  A61K31/70 ,  A61K33/24 ,  A61K38/14 ,  A61K41/0076 ,  A61K31/335 ,  A61K2300/00

Abstract: Methods for cancer chemosensitization are provided. Texaphyrins are new chemosensitizers for enhancing the cytotoxicity of chemotherapeutic agents. The enhancement appears to be P-glycoprotein-independent since texaphyrins are effective in both a P-glycoprotein-expressing and a P-glycoprotein-nonexpressing cell line. Methods are provided for the treatment of cancers such as leukemia, lymphoma, carcinoma, and sarcoma using a texaphyrin as a chemosensitizer.

Abstract translation: 提供了癌症化学敏化方法。 Texaphyrins是增加化学治疗剂细胞毒性的新型化学增敏剂。 增强似乎是P-糖蛋白不依赖性，因为泰克萨菲精对p-糖蛋白表达和P-糖蛋白无影响的细胞系都有效。 提供了使用泰克萨菲瑞作为化学敏化剂治疗癌症如白血病，淋巴瘤，癌和肉瘤的方法。

公开(公告)号：WO1996038461A1

公开(公告)日：1996-12-05

申请号：PCT/US1996008262

申请日：1996-05-31

Applicant: PHARMACYCLICS, INC. ,  BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM ,  MAGDA, Darren ,  SESSLER, Jonathan, L.

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

IPC: C07H21/00

CPC classification number: C12N15/113 ,  A61K41/0038 ,  A61K41/0042 ,  A61K41/0076 ,  A61K47/546 ,  A61K49/0021 ,  B01J31/1815 ,  B01J2531/025 ,  B01J2531/36 ,  C07D487/22 ,  C07H21/00 ,  C12N2310/15 ,  C12N2310/321 ,  C12N2310/3511 ,  C12N2310/3527 ,  C12N2310/3521

Abstract: A particular class of metal complexes, specifically certain texaphyrin metal complexes, which both hydrolyze and photocleave ribonucleic acid, and which also both hydrolyze ribonucleic acid and photocleave deoxyribonucleic acid, is provided. The texaphyrin metal complex for each set of reactions has catalytic activity for phosphate ester hydrolysis and is photosensitive. A complex having the advantage of multiple activities can result in lower treatment dosages and lower treatment costs.

Abstract translation: 提供了特殊类别的金属络合物，特别是水解和光切核糖核酸的某些特沙弗林金属络合物，并且还水解核糖核酸和光切割脱氧核糖核酸。 用于每组反应的泰克萨菲金属络合物对磷酸酯水解具有催化活性并且是光敏的。 具有多种活性优点的复合物可以降低治疗剂量并降低治疗成本。

公开(公告)号：WO1996009315A1

公开(公告)日：1996-03-28

申请号：PCT/US1995012312

申请日：1995-09-21

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

Inventor： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM ,  PHARMACYCLICS, INC. ,  MAGDA, Darren ,  SESSLER, Jonathan, L. ,  IVERSON, Brent, L. ,  SANSOM, Petra, I. ,  WRIGHT, Meredith ,  MODY, Tarak, D. ,  HEMMI, Gregory, W.

IPC: C07H21/00

CPC classification number: C12N15/113 ,  A61K41/0038 ,  A61K41/0042 ,  A61K41/0076 ,  A61K47/54 ,  A61K47/546 ,  A61K49/0021 ,  A61K49/0052 ,  A61K49/0054 ,  A61K49/06 ,  A61K49/085 ,  A61K49/10 ,  A61K51/0485 ,  A61L2/0011 ,  B01J31/061 ,  B01J31/1658 ,  B01J31/1815 ,  B01J2531/025 ,  B01J2531/38 ,  C07D487/22 ,  C07H21/00 ,  C12N2310/15 ,  C12N2310/321 ,  C12N2310/3511 ,  Y10T436/147777 ,  C12N2310/3521

Abstract: Methods of cleavage of a polymer of deoxyribonucleic acid using photosensitive texaphyrins are disclosed. A preferred method of use is the site-specific cleavage of a polymer of deoxyribonucleic acid, and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directing molecule, preferably an oligonucleotide.

Abstract translation: 公开了使用光敏泰克萨菲蛋白分解脱氧核糖核酸聚合物的方法。 优选的使用方法是脱氧核糖核酸的聚合物的位点特异性切割，并且优选的泰克萨菲瑞是具有结合特异性的衍生化泰克萨菲林，特别是共价偶联到位点定向分子，优选寡核苷酸的泰克萨菲林。

公开(公告)号：WO9429316A3

公开(公告)日：1995-02-02

申请号：PCT/US9406284

申请日：1994-06-09

Applicant: UNIV TEXAS ,  PHARMACYCLICS INC ,  SESSLER JONATHAN L ,  ROSS KEVIN L ,  WRIGHT MEREDITH ,  HEMMI GREGORY W ,  DOW WILLIAM C ,  SMITH DANIEL A ,  KRAL VLADIMIR A ,  IVERSON BRENT ,  MODY TARAK ,  MILLER RICHARD A ,  MAGDA DARREN

Inventor： SESSLER JONATHAN L ,  ROSS KEVIN L ,  WRIGHT MEREDITH ,  HEMMI GREGORY W ,  DOW WILLIAM C ,  SMITH DANIEL A ,  KRAL VLADIMIR A ,  IVERSON BRENT ,  MODY TARAK ,  MILLER RICHARD A ,  MAGDA DARREN

IPC: A61K41/00 ,  A61K47/48 ,  A61K49/00 ,  A61K49/06 ,  A61K49/08 ,  A61K51/04 ,  A61L2/00 ,  B01J31/06 ,  B01J31/16 ,  B01J31/18 ,  C07B61/00 ,  C07D487/22 ,  C07F9/06 ,  C07F9/6558 ,  C07F9/6561 ,  C07H21/00 ,  C12N15/10 ,  C12Q1/68

CPC classification number: C07D487/22 ,  A61K41/0038 ,  A61K41/0076 ,  A61K47/546 ,  A61K49/0021 ,  A61K49/0036 ,  A61K49/085 ,  A61K49/106 ,  A61K49/126 ,  A61K51/0485 ,  A61L2/0011 ,  B01J31/061 ,  B01J31/1658 ,  B01J31/1815 ,  B01J2531/025 ,  B01J2531/23 ,  B01J2531/26 ,  B01J2531/27 ,  B01J2531/28 ,  B01J2531/38 ,  B01J2531/72 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  B01J2531/96 ,  C07H21/00

Abstract: A method of phosphate ester hydrolysis including incubating a solution of an aqueous phosphate ester with a texaphyrin metal complex. The metal is a metal cation having catalytic activity for ester bond hydrolysis in aqueous solution, in particular, a lanthanide metal cation, preferably Eu(III) or Dy(III). A preferred substrate is RNA and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directed molecule, preferably an oligonucleotide.

公开(公告)号：WO1994029316A2

公开(公告)日：1994-12-22

申请号：PCT/US1994006284

申请日：1994-06-09

Applicant: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM ,  PHARMACYCLICS, INC. ,  SESSLER, Jonathan, L. ,  ROSS, Kevin, L. ,  WRIGHT, Meredith ,  HEMMI, Gregory, W. ,  DOW, William, C. ,  SMITH, Daniel, A. ,  KRAL, Vladimir, A. ,  IVERSON, Brent ,  MODY, Tarak ,  MILLER, Richard, A. ,  MAGDA, Darren

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

IPC: C07D487/22

CPC classification number: C07D487/22 ,  A61K41/0038 ,  A61K41/0076 ,  A61K47/546 ,  A61K49/0021 ,  A61K49/0036 ,  A61K49/085 ,  A61K49/106 ,  A61K49/126 ,  A61K51/0485 ,  A61L2/0011 ,  B01J31/061 ,  B01J31/1658 ,  B01J31/1815 ,  B01J2531/025 ,  B01J2531/23 ,  B01J2531/26 ,  B01J2531/27 ,  B01J2531/28 ,  B01J2531/38 ,  B01J2531/72 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  B01J2531/96 ,  C07H21/00

Abstract: A method of phosphate ester hydrolysis including incubating a solution of an aqueous phosphate ester with a texaphyrin metal complex. The metal is a metal cation having catalytic activity for ester bond hydrolysis in aqueous solution, in particular, a lanthanide metal cation, preferably Eu(III) or Dy(III). A preferred substrate is RNA and a preferred texaphyrin is a derivatized texaphyrin having binding specificity, in particular, a texaphyrin covalently coupled to a site-directed molecule, preferably an oligonucleotide.

Abstract translation: 磷酸酯水解方法，包括将磷酸酯水溶液与泰克萨菲金属络合物的溶液孵育。 金属是具有催化活性的金属阳离子，用于水溶液中的酯键水解，特别是镧系元素金属阳离子，优选Eu（III）或Dy（III）。 优选的底物是RNA，优选的泰克萨菲瑞是具有结合特异性的衍生的泰克萨菲林，特别是共价偶联到定点分子，优选寡核苷酸的泰克萨菲林。

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：US20150306103A1

公开(公告)日：2015-10-29

申请号：US14613309

申请日：2015-02-03

Applicant: Pharmacyclics, Inc.

Inventor： Lee HONIGBERG ,  Erik VERNER ,  Zhengying PAN

IPC: A61K31/519 ,  A61K45/06

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：US09133134B2

公开(公告)日：2015-09-15

申请号：US14401104

申请日：2013-05-15

Applicant: Pharmacyclics, Inc.

Inventor： Wei Chen ,  David J. Loury ,  Tarak D. Mody

IPC: C07D239/48 ,  A61K31/505

CPC classification number: C07D239/48 ,  A61K31/505

Abstract: Described herein are kinase inhibitor compounds, methods for synthesizing such inhibitors, and methods for using such inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate inhibitor of a protein, including a kinase.

Abstract translation: 本文描述的是激酶抑制剂化合物，用于合成这种抑制剂的方法，以及在治疗疾病中使用这些抑制剂的方法。 本文进一步描述了用于测定包括激酶在内的蛋白质的适当抑制剂的方法，测定和系统。