公开(公告)号：WO2005032488A3

公开(公告)日：2005-05-12

申请号：PCT/US2004032921

申请日：2004-09-29

Applicant: PORTOLA PHARM INC ,  SCARBOROUGH ROBERT M ,  HUANG WOLIN ,  PANDEY ANJALI ,  BAUER SHAWN M ,  ZHANG XIAOMING ,  JIA ZHAOZHONG J

Inventor： SCARBOROUGH ROBERT M ,  HUANG WOLIN ,  PANDEY ANJALI ,  BAUER SHAWN M ,  ZHANG XIAOMING ,  JIA ZHAOZHONG J

IPC: A61K20060101 ,  A61K31/517 ,  A61P7/02 ,  C07D409/12 ,  C07D409/14

CPC classification number: C07D409/12 ,  C07D409/14

Abstract: 2,4-Dioxo-3-quinazolinylaryl sulfonylurea compounds are provided that are useful for the inhibition of ADP-platelet aggregation, particularly in the treatment of thrombosis and thrombosis related conditions or disorders.

Abstract translation: 提供了2,4-二氧代-3-喹唑啉基芳基磺酰脲化合物，其用于抑制ADP-血小板聚集，特别是在治疗血栓形成和血栓形成相关病症或病症中。

公开(公告)号：WO2012061418A3

公开(公告)日：2012-08-02

申请号：PCT/US2011058826

申请日：2011-11-01

Applicant: PORTOLA PHARM INC ,  JIA ZHAOZHONG J ,  SONG YONGHONG ,  XU QING ,  KANE BRIAN ,  BAUER SHAWN M ,  PANDEY ANJALI

Inventor： JIA ZHAOZHONG J ,  SONG YONGHONG ,  XU QING ,  KANE BRIAN ,  BAUER SHAWN M ,  PANDEY ANJALI

IPC: C07D213/82 ,  A61K31/455 ,  A61P35/00 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D495/04

CPC classification number: C07C237/42 ,  C07C237/30 ,  C07C2601/14 ,  C07D209/08 ,  C07D209/40 ,  C07D213/74 ,  C07D213/82 ,  C07D231/12 ,  C07D231/38 ,  C07D233/56 ,  C07D239/48 ,  C07D249/06 ,  C07D249/08 ,  C07D257/04 ,  C07D261/14 ,  C07D275/03 ,  C07D277/42 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04

Abstract: The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.

Abstract translation: 本发明涉及作为Syk激酶抑制剂的式I化合物及其药学上可接受的盐，酯和前药。 本发明还涉及用于制备这类化合物的中间体，这种化合物的制备，含有这种化合物的药物组合物，抑制Syk激酶活性的方法，抑制血小板聚集的方法以及预防或治疗一些 至少部分由Syk激酶活性介导的病症，如非霍奇金淋巴瘤。

公开(公告)号：WO2010057036A3

公开(公告)日：2011-06-09

申请号：PCT/US2009064455

申请日：2009-11-13

Applicant: PORTOLA PHARM INC ,  PATHEON INC ,  RAMANI CHANDIR ,  WANG JUAN ,  KANE ANIL ,  CHOW KWOK ,  LAMBING JOE

Inventor： RAMANI CHANDIR ,  WANG JUAN ,  KANE ANIL ,  CHOW KWOK ,  LAMBING JOE

IPC: A61K9/20 ,  A61K31/19 ,  A61K31/192 ,  A61K31/405 ,  A61K31/517 ,  A61P7/02 ,  A61P9/00

CPC classification number: A61K47/38 ,  A61K9/0002 ,  A61K9/0065 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2018 ,  A61K9/2027 ,  A61K9/2031 ,  A61K9/205 ,  A61K9/2054 ,  A61K47/10

Abstract: A novel solid composition and methods for making and using the solid composition are provided. The solid composition comprises: (a) at least one active agent with a solubility of less than about 0.3 mg/ml in an aqueous solution with a pH of at most about 6.8 at a temperature of about 37oC; and (b) a hydrophilic polymer matrix composition comprising: i) a hydrophilic polymer selected from the group consisting of METHOCELTM, POLYOXTM WSR 1105 and combinations thereof; and optionally ii) a hydrophobic polymer selected from the group consisting of Ethocel 20 premium; and (c) an alkalizer selected from the group consisting of calcium carbonate, magnesium oxide heavy and sodium bicarbonate; wherein the composition provides at least about 70% release of the active between about 7 to about 12 hours following oral administration.

Abstract translation: 提供了一种新颖的固体组合物和制备和使用该固体组合物的方法。 固体组合物包含：（a）至少一种在约37℃的温度下，pH至多约6.8的水溶液中溶解度小于约0.3mg / ml的活性剂; 和（b）亲水性聚合物基质组合物，其包含：i）选自METHOCEL TM，POLYOXTM WSR 1105的亲水性聚合物及其组合; 和任选地ii）选自Ethocel 20溢价的疏水性聚合物; 和（c）选自碳酸钙，氧化镁重质和碳酸氢钠的碱化剂; 其中所述组合物在口服给药后提供约7至约12小时之间的至少约70％的活性释放。

公开(公告)号：WO2009042962A3

公开(公告)日：2009-06-04

申请号：PCT/US2008078014

申请日：2008-09-26

Applicant: PORTOLA PHARM INC ,  LU GENMIN ,  PHILLIPS DAVID R ,  ANDRE PATRICK ,  SINHA UMA

Inventor： LU GENMIN ,  PHILLIPS DAVID R ,  ANDRE PATRICK ,  SINHA UMA

IPC: C12N9/64 ,  A61P7/04

CPC classification number: A61K38/4846 ,  A61K38/00 ,  A61K38/4826 ,  A61K38/4833 ,  A61K38/4853 ,  A61K39/00 ,  A61K47/60 ,  C07K14/435 ,  C12N9/6432 ,  C12Y304/21006

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract translation: 本发明涉及解毒剂靶向因子Xa的抗凝血剂。 解毒剂是因子Xa蛋白衍生物，其与因子Xa抑制剂结合，从而基本上中和它们但不组装成凝血酶原酶复合物。 本文描述的衍生物缺乏或降低了内在凝固剂活性。 本文公开了停止或预防正在用Xa因子抑制剂进行抗凝血剂治疗的患者出血的方法。

公开(公告)号：WO2007056167A2

公开(公告)日：2007-05-18

申请号：PCT/US2006042998

申请日：2006-11-03

Applicant: PORTOLA PHARM INC ,  PANDEY ANJALI ,  MEHROTRA MUKUND ,  CRUSKIE MICHAEL ,  WHITE DAVID CHARLES ,  YIANNIKOUROS GEORGE PETROS

Inventor： PANDEY ANJALI ,  MEHROTRA MUKUND ,  CRUSKIE MICHAEL ,  WHITE DAVID CHARLES ,  YIANNIKOUROS GEORGE PETROS ,  SCARBOROUGH ROBERT M

IPC: A61K31/517 ,  C07D409/02

CPC classification number: C07D409/12

Abstract: The present invention provides sulfonylurea compounds of formula (VIII) and pharmaceutically acceptable derivatives thereof and a process for making thereof. The compounds in their various forms are effective platelet ADP receptor inhibitors and may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also provides intermediate compounds useful in the process, as well as final products produced by the process, and salts or prodrugs thereof. The invention also provides a method for inhibition platelet ADP receptor and preventing or treating thrombosis and thrombosis related conditions in a mammal comprising the step of administering a therapeutically effective amount of a compound of formula (VIII) or a pharmaceutically acceptable salt or forms thereof.

Abstract translation: 本发明提供了式（VIII）的磺酰脲化合物及其药学上可接受的衍生物及其制备方法。 各种形式的化合物是有效的血小板ADP受体抑制剂，并且可以用于各种药物组合物中，并且特别有效用于预防和/或治疗心血管疾病，特别是与血栓形成相关的疾病。 本发明还提供了用于该方法的中间体化合物，以及由该方法产生的最终产物，及其盐或前体药物。 本发明还提供了抑制血小板ADP受体并预防或治疗哺乳动物血栓形成和血栓形成相关病症的方法，其包括施用治疗有效量的式（VIII）化合物或其药学上可接受的盐或其形式的步骤。

公开(公告)号：WO2006066008A2

公开(公告)日：2006-06-22

申请号：PCT/US2005045445

申请日：2005-12-14

Applicant: PORTOLA PHARM INC ,  PHILLIPS DAVID R ,  ANDRE PATRICK ,  STEPHENS GILLIAN

Inventor： PHILLIPS DAVID R ,  ANDRE PATRICK ,  STEPHENS GILLIAN

IPC: C12Q1/56

CPC classification number: G01N33/9486 ,  G01N33/86

Abstract: The present invention relates to methods and compositions for identifying and treating subjects in need of antithrombotic therapies but who are not responsive to aspirin.

Abstract translation: 本发明涉及用于鉴定和治疗需要抗血栓治疗但是对阿司匹林不敏感的受试者的方法和组合物。

公开(公告)号：WO2009136995A2

公开(公告)日：2009-11-12

申请号：PCT/US2009002401

申请日：2009-04-16

Applicant: PORTOLA PHARM INC ,  JIA ZHAOZHONG J ,  VENKATARAMANI CHANDRASEKAR ,  HUANG WOLIN ,  MEHROTRA MUKUND ,  SONG YONGHONG ,  XU QING ,  BAUER SHAWN M ,  PANDEY ANJALI

Inventor： JIA ZHAOZHONG J ,  VENKATARAMANI CHANDRASEKAR ,  HUANG WOLIN ,  MEHROTRA MUKUND ,  SONG YONGHONG ,  XU QING ,  BAUER SHAWN M ,  PANDEY ANJALI

IPC: C07D239/48 ,  A61K31/506 ,  A61P9/00 ,  A61P35/00 ,  C07D401/12 ,  C07D403/12 ,  C07D407/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

CPC classification number: C07D239/48 ,  C07D401/12 ,  C07D403/12 ,  C07D407/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

Abstract: The present invention is directed to compounds of formula I-V and tattooers thereof or pharmaceutically acceptable salts, esters, and pro drugs thereof which are inhibitors of sky kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by syk kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

Abstract translation: 本发明涉及作为天sky素抑制剂的式I-V化合物及其纹身或其药学上可接受的盐，酯和其前体药物。 本发明还涉及用于制备这种化合物的中间体，这种化合物的制备，含有这种化合物的药物组合物，抑制syk激酶活性的方法，抑制血小板聚集的方法，以及预防或治疗数字的方法 至少部分通过syk激酶活性介导的病症，例如不期望的血栓形成和非霍奇金淋巴瘤。

公开(公告)号：WO2009042962A2

公开(公告)日：2009-04-02

申请号：PCT/US2008078014

申请日：2008-09-26

Applicant: PORTOLA PHARM INC ,  LU GENMIN ,  PHILLIPS DAVID R ,  ANDRE PATRICK ,  SINHA UMA

Inventor： LU GENMIN ,  PHILLIPS DAVID R ,  ANDRE PATRICK ,  SINHA UMA

IPC: A61P7/02 ,  A61K31/4545 ,  A61K31/5377 ,  A61K31/715 ,  A61K31/727 ,  A61K38/36 ,  A61K38/48 ,  A61K39/395 ,  A61K47/48 ,  A61P7/04 ,  C07H21/00 ,  C07K14/00 ,  C07K16/00 ,  C12N5/10 ,  C12P21/00

CPC classification number: A61K38/4846 ,  A61K38/00 ,  A61K38/4826 ,  A61K38/4833 ,  A61K38/4853 ,  A61K39/00 ,  A61K47/60 ,  C07K14/435 ,  C12N9/6432 ,  C12Y304/21006

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract translation: 本发明涉及靶向因子Xa的抗凝剂的解毒剂。 解毒剂是与因子Xa抑制剂结合的因子Xa蛋白衍生物，从而基本上中和它们，但不组装到凝血酶原酶复合物中。 本文所述的衍生物缺乏或具有降低的内在凝结剂活性。 本文公开了在目前正在进行使用因子Xa抑制剂进行抗凝治疗的患者中停止或预防出血的方法。

公开(公告)号：WO2008137787A3

公开(公告)日：2009-02-05

申请号：PCT/US2008062561

申请日：2008-05-02

Applicant: PORTOLA PHARM INC ,  CONLEY PAMELA B ,  ANDRE PATRICK ,  SINHA UMA

Inventor： CONLEY PAMELA B ,  ANDRE PATRICK ,  SINHA UMA

IPC: A61K31/235 ,  A61K31/422 ,  A61K31/435 ,  A61K31/517 ,  A61K45/06 ,  A61P7/00 ,  A61P7/02 ,  A61P9/00

CPC classification number: A61K31/422 ,  A61K31/235 ,  A61K31/435 ,  A61K31/4545 ,  A61K31/517 ,  A61K38/4846 ,  A61K45/06 ,  A61K2300/00

Abstract: The present invention is directed to pharmaceutical compositions and methods of using combination therapies containing [4 (6-fluoro-7-methylamino-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-phenyl]-5-chloro-thiophen-2-yl-sulfonylurea, or a pharmaceutically acceptable salt thereof, for the treatment of thrombosis diseases.

Abstract translation: 本发明涉及药物组合物和使用含有[4（6-氟-7-甲基氨基-2,4-二氧代-1,4-二氢-2H-喹唑啉-3-基） - 苯基] - 5-氯 - 噻吩-2-基 - 磺酰脲或其药学上可接受的盐，用于治疗血栓形成疾病。

公开(公告)号：WO2008121721A3

公开(公告)日：2009-01-08

申请号：PCT/US2008058469

申请日：2008-03-27

Applicant: PORTOLA PHARM INC ,  SIMS PETER J ,  CONLEY PAMELA B ,  LUAN PENG ,  PHILLIPS DAVID R

Inventor： SIMS PETER J ,  CONLEY PAMELA B ,  LUAN PENG ,  PHILLIPS DAVID R

IPC: A61K9/127

CPC classification number: A61K9/1271 ,  A61K9/1272 ,  A61K31/685 ,  A61K38/177 ,  A61K38/46 ,  A61K47/6843 ,  A61K47/6913 ,  A61K2300/00

Abstract: A platelet substitute consisting of large unilamellar lipid vesicles that contain phosphatidylserine or another procoagulant (clot-promoting) phospholipid, a protein that has binding affinity for collagen or other component of the vessel wall that becomes exposed upon vessel injury, and/or a phospholipid scramblase, has been developed. This platelet substitute provides a means for selectively delivering procoagulant phospholipids and/or fatty acids to the site of vessel injury through targeted adherence to collagen or other component exposed upon vessel injury. These are particularly effective due to the combination of targeting procoagulant vesicles to a site of injury, and triggered exposure of phosphatidylserine (PS) on the surface.

Abstract translation: 包含含有磷脂酰丝氨酸或另一促凝血素（促凝血素）磷脂的大单层脂质囊泡的血小板替代物，对血管损伤时暴露于血管壁的胶原蛋白或其他成分具有结合亲和力的蛋白质和/或磷脂类 ，已经开发。 该血小板替代物提供了通过靶向粘附到血管损伤时暴露于胶原或其它组分的选择性地将促凝血磷脂和/或脂肪酸输送到血管损伤部位的手段。 由于靶向促凝血小泡与损伤部位的结合，并且触发表面上的磷脂酰丝氨酸（PS）的暴露，这些是特别有效的。