公开(公告)号：WO1995004136A1

公开(公告)日：1995-02-09

申请号：PCT/US1994008571

申请日：1994-07-29

Applicant: COR THERAPEUTICS, INC. ,  GIESE, Neill, A.

Inventor： COR THERAPEUTICS, INC.

IPC: C12N09/12

CPC classification number: G01N33/5008 ,  G01N2333/9121

Abstract: Methods are provided for assaying the function (e.g., activation) of signal-transducing receptors on cells. The methods are useful for identifying compounds that are agonists or antagonists of receptor function. The assays utilize a two-antibody sandwich assay employing an immobilized first antibody that specifically binds and captures the receptor of interest along with any tightly associated proteins or polypeptides and a second antibody directed against (i) an epitope of the receptor that is characteristic of the activated but not the unactivated state, (ii) an epitope of a protein or molecule characteristically bound to activated receptor but not to unactivated receptor, or (iii) an epitope of the receptor that is characteristic of the unactivated but not the activated state. In one embodiment, the level of binding of the second antibody is determined and correlated with the presence of activated receptor, and thus with activation in response to the treatment received by the cells. The methods provided by the invention will find particular use for detecting activation of tyrosine kinase growth factor receptors.

Abstract translation: 提供了用于测定细胞上信号转导受体的功能（例如激活）的方法。 该方法可用于鉴定作为受体功能的激动剂或拮抗剂的化合物。 该测定法利用采用固定化的第一抗体的双抗体夹心测定法，其特异性结合并捕获感兴趣的受体以及任何紧密相关的蛋白质或多肽，以及针对（i）受体表位的第二抗体，其特征在于 活化但不是未活化状态，（ii）特征性结合活化受体但不结合未活化受体的蛋白质或分子的表位，或（iii）受体的表位，其是未活化但不是活化状态的特征。 在一个实施方案中，确定第二抗体的结合水平并与活化受体的存在相关，并因此响应于由细胞接受的治疗而激活。 本发明提供的方法将特别用于检测酪氨酸激酶生长因子受体的活化。

公开(公告)号：WO1992014750A1

公开(公告)日：1992-09-03

申请号：PCT/US1992001312

申请日：1992-02-19

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  COR THERAPEUTICS, INC.

Inventor： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  COR THERAPEUTICS, INC. ,  COUGHLIN, Shaun, R. ,  SCARBOROUGH, Robert, M.

IPC: C07K07/00

CPC classification number: C12N9/6429 ,  A61K38/00 ,  A61K39/00 ,  C07K14/705 ,  C07K16/28 ,  C12Y304/21005 ,  Y10S530/837

Abstract: The DNA encoding the cell surface receptor for thrombin has been cloned and sequenced. The availability of this DNA permits the recombinant production of thrombin receptor which can be produced at cell surfaces and is useful in assay systems both for the detection of thrombin and for the evaluation of candidate thrombin agonists and antagonists. Further, the elucidation of the structure of the thrombin receptor permits the design of agonist and antagonist compounds which are useful diagnostically and therapeutically. The availability of the thrombin receptor also permits production of antibodies specifically immunoreactive with the receptor per se or with specific regions thereof which are also useful diagnostically or therapeutically.

Abstract translation: 编码凝血酶细胞表面受体的DNA已被克隆并测序。 该DNA的可用性允许重组产生可在细胞表面产生的凝血酶受体，并且可用于检测凝血酶和用于评价候选凝血酶激动剂和拮抗剂的测定系统。 此外，阐明凝血酶受体的结构允许设计在诊断和治疗上有用的激动剂和拮抗剂化合物。 凝血酶受体的可用性还允许产生与受体本身或其特异性区域特异性免疫反应的抗体，其在诊断或治疗上也是有用的。

公开(公告)号：WO0194335A8

公开(公告)日：2003-11-06

申请号：PCT/US0117980

申请日：2001-06-01

Applicant: LILLY CO ELI ,  COR THERAPEUTICS INC ,  BRIGGS BARBARA ,  HANSEN MARVIN ,  KANTER JAMES ,  MULLINS JOHN J G ,  RUHTER GERD ,  UDODONG UKO ,  VERRAL DANIEL II ,  ZMIJEWSKI MILTON JR

Inventor： BRIGGS BARBARA ,  HANSEN MARVIN ,  KANTER JAMES ,  MULLINS JOHN J G ,  RUHTER GERD ,  UDODONG UKO ,  VERRAL DANIEL II ,  ZMIJEWSKI MILTON JR

IPC: A61K31/353 ,  A61P7/02 ,  C07D311/22 ,  C07D311/24 ,  C07D311/58 ,  C07D311/74 ,  C07D311/70

CPC classification number: C07D311/74 ,  A61K31/353 ,  C07D311/22 ,  C07D311/24 ,  C07D311/58

Abstract: Disclosed are process steps and novel processes for producing chromane compositions enriched in at least one (2R or 2S) enantiomer, preferably chroman-2-yl carboxylic acid compounds and chroman-2-yl carboxylic acid esters which are intermediates for producing platelet aggregation inhibitors and/or are themselves potent platelet aggregation inhibitors. Further disclosed are enzymatic processes for resolving chiral intermediates or final products to provide desired enantiomers.

Abstract translation: 公开了生产富集至少一种（2R或2S）对映异构体，优选苯并二氢吡喃-2-基羧酸化合物和色满-2-基羧酸酯的色淀组合物的方法步骤和新方法，其是制备血小板聚集抑制剂的中间体， /或本身是有效的血小板聚集抑制剂。 进一步公开的是用于拆分手性中间体或最终产物以提供所需对映异构体的酶法。

公开(公告)号：WO0194330A8

公开(公告)日：2003-11-06

申请号：PCT/US0117688

申请日：2001-06-01

Applicant: COR THERAPEUTICS INC ,  KANTER JAMES ,  MULLINS JOHN J G ,  SCARBOROUGH ROBERT ,  WALKER DERRICK ,  HENSE THOMAS

Inventor： KANTER JAMES ,  MULLINS JOHN J G ,  SCARBOROUGH ROBERT ,  WALKER DERRICK ,  HENSE THOMAS

IPC: A61P7/00 ,  C07D311/20 ,  C07D311/22 ,  C07D311/58 ,  C07D311/70 ,  A61K31/35

CPC classification number: C07D311/22 ,  C07D311/20 ,  C07D311/58

Abstract: Disclosed are processes for producing chromane compounds, preferably chroman-2-yl acetic acid compounds and 6-amino-chroman-2-yl acetic acid esters which are intermediates for producing platelet aggregation inhibitors and/or are themselves potent platelet aggregation inhibitors.

Abstract translation: 本发明公开了生产色氨酸化合物，优选苯并二氢吡喃-2-基乙酸化合物和6-氨基 - 苯并二氢吡喃-2-基乙酸酯的方法，其为制备血小板聚集抑制剂的中间体和/或本身是有效的血小板聚集抑制剂。

公开(公告)号：WO0112600A9

公开(公告)日：2002-09-12

申请号：PCT/US0021742

申请日：2000-08-10

Applicant: COR THERAPEUTICS INC ,  ZHU BING-YAN ,  SCARBOROUGH ROBERT M ,  CLIZBE LANE ,  DOUGHAN BRANDON ,  JIA ZHAOZHONG-JON ,  KANE-MAGUIRE KIM ,  MARLOWE CHARLES ,  SONG YONGHONG ,  SU TING ,  TENG WILLY ,  ZHANG PENGLIE

Inventor： ZHU BING-YAN ,  SCARBOROUGH ROBERT M ,  CLIZBE LANE ,  DOUGHAN BRANDON ,  JIA ZHAOZHONG-JON ,  KANE-MAGUIRE KIM ,  MARLOWE CHARLES ,  SONG YONGHONG ,  SU TING ,  TENG WILLY ,  ZHANG PENGLIE

IPC: C07D209/08 ,  C07D209/34 ,  C07D209/38 ,  C07D215/08 ,  C07D215/22 ,  C07D215/227 ,  C07D231/56 ,  C07D235/06 ,  C07D235/26 ,  C07D241/38 ,  C07D241/44 ,  C07D243/24 ,  C07D265/36 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D409/06 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D209/04 ,  C07D215/00 ,  C07D235/04 ,  C07D241/36 ,  C07D403/02 ,  C07D498/02

CPC classification number: C07D215/227 ,  C07D209/08 ,  C07D209/34 ,  C07D209/38 ,  C07D215/08 ,  C07D231/56 ,  C07D235/06 ,  C07D235/26 ,  C07D241/38 ,  C07D241/44 ,  C07D243/24 ,  C07D265/36 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D409/06 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

Abstract: Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds of formula (I) are useful in vitro or in vivo for preventing or treating coagulation disorders.

Abstract translation: 公开了与哺乳动物因子Xa具有活性的新型化合物，其盐和与其相关的组合物。 式（I）化合物在体外或体内可用于预防或治疗凝血障碍。

公开(公告)号：WO0216360A3

公开(公告)日：2002-06-13

申请号：PCT/US0141749

申请日：2001-08-17

Applicant: COR THERAPEUTICS INC ,  KYOWA HAKKO KOGYO KK ,  PANDEY ANJALI ,  SCARBOROUGH ROBERT M ,  MATSUNO KENJI ,  ICHIMURA MICHIO ,  NOMOTO YUJI ,  FUJIWARA SHIGEKI ,  IDE SHINICHI ,  TSUKUDA EIJI ,  IRIE JUNKO ,  ODA SHOJI

Inventor： PANDEY ANJALI ,  SCARBOROUGH ROBERT M ,  MATSUNO KENJI ,  ICHIMURA MICHIO ,  NOMOTO YUJI ,  FUJIWARA SHIGEKI ,  IDE SHINICHI ,  TSUKUDA EIJI ,  IRIE JUNKO ,  ODA SHOJI

IPC: A61P35/00 ,  C07D239/94 ,  C07D401/12 ,  C07D403/12 ,  A61K31/517 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

CPC classification number: C07D401/12 ,  C07D239/94 ,  C07D403/12

Abstract: The present invention relates to nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which have inhibitory activity on the phosphorylation of kinases, which inhibits the activity of such kinases. The invention is also related to a method of inhibiting kinases and treating disease states in a mammal by inhibiting the phosphorylation of kinases. In a particular aspect the present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of a PDGF receptor to hinder abnormal cell growth and cell wandering, and a method for preventing or treating cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis.

Abstract translation: 本发明涉及对抑制这种激酶活性的激酶磷酸化具有抑制活性的含氮杂环化合物及其药学上可接受的盐。 本发明还涉及通过抑制激酶的磷酸化来抑制哺乳动物的激酶和治疗疾病状态的方法。 在一个特定方面，本发明提供了抑制PDGF受体的磷酸化以阻止异常细胞生长和细胞游动的含氮杂环化合物及其药学上可接受的盐，以及预防或治疗细胞增殖性疾病如动脉硬化，血管 重建，癌症和肾小球硬化症。

公开(公告)号：WO0172708A3

公开(公告)日：2002-05-23

申请号：PCT/US0109374

申请日：2001-03-26

Applicant: COR THERAPEUTICS INC ,  MARLOWE CHARLES K ,  KANE MAGUIRE KIM A ,  ZHU BING YAN ,  SCARBOROUGH ROBERT M

Inventor： MARLOWE CHARLES K ,  KANE-MAGUIRE KIM A ,  ZHU BING-YAN ,  SCARBOROUGH ROBERT M

IPC: A61P7/02 ,  C07D401/12 ,  A61K31/454

CPC classification number: C07D401/12

Abstract: Novel compounds of formula (I), including its pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa is described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating conditions in mammals characterized by undesired thrombosis.

Abstract translation: 描述了新的式（I）化合物，包括其药学上可接受的异构体，盐，水合物，溶剂合物和具有抗哺乳动物因子Xa活性的前药衍生物。 还描述了含有这些化合物的组合物。 化合物和组合物在体外或体内用于预防或治疗特征在于不期望的血栓形成的哺乳动物中的病症。

公开(公告)号：WO0226712A2

公开(公告)日：2002-04-04

申请号：PCT/US0142352

申请日：2001-10-01

Applicant: COR THERAPEUTICS INC ,  ZHANG PENGLIE ,  ZUCKETT JINGMEI FAN ,  BAO LIANG ,  SCARBOROUGH ROBERT M ,  ZHU BING YAN

Inventor： ZHANG PENGLIE ,  ZUCKETT JINGMEI FAN ,  BAO LIANG ,  SCARBOROUGH ROBERT M ,  ZHU BING-YAN

IPC: A61P7/00 ,  C07D213/74 ,  C07D213/81 ,  C07D409/12 ,  C07D213/00

CPC classification number: C07D213/74 ,  C07D213/81 ,  C07D409/12

Abstract: Novel quaternary amine-containing compounds including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating conditions in mammals characterized by undesired thrombosis.

Abstract translation: 描述了具有抗哺乳动物因子Xa的活性的新型含季铵化合物，包括其药学上可接受的异构体，盐，水合物，溶剂合物和前药衍生物。 还描述了含有这些化合物的组合物。 化合物和组合物可用于体外或体内用于预防或治疗特征在于不希望的血栓形成的哺乳动物的状况。

公开(公告)号：WO0164643A3

公开(公告)日：2002-04-04

申请号：PCT/US0106255

申请日：2001-02-28

Applicant: COR THERAPEUTICS INC ,  ZHU BING YAN ,  ZHANG PENGLIE ,  WANG LINGYAN ,  HUANG WENRONG ,  GOLDMAN ERICK ,  LI WENHAO ,  ZUCKETT JINGMEI ,  SONG YONGHONG ,  SCARBOROUGH ROBERT

Inventor： ZHU BING-YAN ,  ZHANG PENGLIE ,  WANG LINGYAN ,  HUANG WENRONG ,  GOLDMAN ERICK ,  LI WENHAO ,  ZUCKETT JINGMEI ,  SONG YONGHONG ,  SCARBOROUGH ROBERT

IPC: A61K31/443 ,  A61K31/444 ,  A61P7/02 ,  C07C311/16 ,  C07C311/46 ,  C07C317/40 ,  C07C317/44 ,  C07D213/75 ,  C07D213/81 ,  C07D213/82 ,  C07D217/22 ,  C07D333/38 ,  C07D401/12 ,  C07D409/12 ,  C07D409/14 ,  C07D521/00 ,  A61K31/44

CPC classification number: A61K31/44 ,  A61K9/20 ,  A61K9/2013 ,  A61K9/2054 ,  A61K9/48 ,  A61K9/4858 ,  A61K9/4866 ,  A61K31/616 ,  A61K45/06 ,  A61K2201/094 ,  C07C237/42 ,  C07C255/60 ,  C07C257/18 ,  C07C259/18 ,  C07C311/16 ,  C07C311/46 ,  C07C317/40 ,  C07C317/44 ,  C07D213/75 ,  C07D213/81 ,  C07D213/82 ,  C07D217/22 ,  C07D231/12 ,  C07D233/56 ,  C07D233/64 ,  C07D249/08 ,  C07D295/125 ,  C07D333/38 ,  C07D401/12 ,  C07D409/12 ,  C07D409/14

Abstract: Benzamide compounds of the formulae (VI) and (VII), where the variables are as defined in the claims, including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating coagulation disorders.

Abstract translation: 描述式（VI）和（VII）的苯甲酰胺化合物，其中变量如权利要求中所定义，包括其对哺乳动物因子Xa具有活性的药学上可接受的异构体，盐，水合物，溶剂合物和前药衍生物。 还描述了含有这些化合物的组合物。 化合物和组合物可用于体内或体内用于预防或治疗凝血障碍。

公开(公告)号：WO0179144A3

公开(公告)日：2002-02-28

申请号：PCT/US0112039

申请日：2001-04-13

Applicant: COR THERAPEUTICS INC ,  COWAN KYRA J ,  LAW DEBBIE A ,  PHILLIPS DAVID R

Inventor： COWAN KYRA J ,  LAW DEBBIE A ,  PHILLIPS DAVID R

IPC: C07K14/705 ,  C12N9/12 ,  C07K14/00

CPC classification number: C07K14/70557 ,  C07K14/7055 ,  C07K14/70553

Abstract: The present invention describes a direct interaction between phosphorylated GPIIIa cytoplasmic domains with 1) src/ non- src family kinases and 2) phosphatases. The invention provides methods for identifying agents that block GPIIIa interactions with src/ non- scr family kinases and phosphatases, methods of using agents that block GPIIIa interactions with src/ non- src family kinases and PIP-1C phosphatases to modulate biological and pathological processes and agents that block GPIIIa mediated binding to src/ non- scr family kinases and PIP-1C phosphatases, thereby modulating related GPIIIa mediated signaling.

Abstract translation: 本发明描述了磷酸化GPIIIa细胞质结构域与1）src /非src家族激酶和2）磷酸酶之间的直接相互作用。 本发明提供用于鉴定阻断GPIIIa与非特异性家族激酶和磷酸酶的GPIIIa相互作用的试剂的方法，使用阻断GPIIIa与src / 非激活家族激酶和PIP-1C磷酸酶调节生物学和病理学过程，并阻断GPIIIa介导的结合于src / 家族激酶和PIP-1C磷酸酶，从而调节相关的GPIIIa介导的信号传导。