公开(公告)号：US20050112693A1

公开(公告)日：2005-05-26

申请号：US10972742

申请日：2004-10-25

Applicant: Adel Nefzi ,  John Ostresh ,  Richard Houghten

Inventor： Adel Nefzi ,  John Ostresh ,  Richard Houghten

IPC: C07B61/00 ,  C07D233/36 ,  C07D233/42 ,  C07D239/10 ,  C07D241/18 ,  C07D243/08 ,  C07D245/04 ,  C07D245/06 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  G01N33/53 ,  C07D487/02

CPC classification number: C07D487/04 ,  C07D233/36 ,  C07D233/42 ,  C07D239/10 ,  C07D241/18 ,  C07D243/08 ,  C07D245/04 ,  C07D245/06 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04 ,  C40B40/00 ,  C40B40/04 ,  C40B50/14

Abstract: The synthesis of individual di- and tri-substituted-1,4-diazacyclic compounds having 6- to 8-atoms in the cyclic ring, their corresponding 1,6-diketo-2,5-diazacyclic compounds and similar 1,4-diazacyclic ring compounds having one ring carbonyl gorup and 6-8 atoms in the ring is disclosed, as are libraries of such compounds. Methods of preparing and using the libraries of compounds as well as individual compounds of the libraries are also disclosed.

Abstract translation: 在环中具有6-8个原子的单个二 - 和三 - 取代-1,4-二氮环化合物，它们相应的1,6-二酮-2,5-二氮杂环化合物和类似的1,4-二氮杂环 公开了环中具有一个环羰基羰基和6-8个原子的环化合物，以及这些化合物的文库。 还公开了制备和使用化合物文库以及文库的单独化合物的方法。

公开(公告)号：US20050119176A1

公开(公告)日：2005-06-02

申请号：US10748128

申请日：2003-12-24

Applicant: John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

Inventor： John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

IPC: A61K38/00 ,  C07K5/10 ,  C07K5/103 ,  C07K5/107 ,  C07K5/11 ,  C07K5/117 ,  C07K7/06 ,  C12N9/99 ,  A61K38/52

CPC classification number: C07K5/1008 ,  A61K38/00 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1024 ,  C07K5/1027 ,  C07K7/06

Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24, a core structure selected from the group of TPI 759, TPI 882, TPI 914 or TPI 927; and a core structure from a library selected from TPI 1391, TPI 1349, TPI 1396, TPI 1509, TPI 1540, TPI 1400, TPI 792 and TPI 1332, wherein the agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase.

Abstract translation: 本发明提供了具有选自核心肽5至39和42至55的核心肽的分离的试剂，其中所述试剂减阻IAP抑制的半胱天冬酶。 还提供了一种隔离剂，其具有选自图中的任何一种结构的核心结构。 5,9，10,114和21-24，选自TPI 759，TPI 882，TPI 914或TPI 927的核心结构; 以及来自选自TPI1391，TPI1349，TPI1396，TPI1509，TPI1540，TPI1400，TPI792和TPI1332的文库的核心结构，其中所述试剂去抑制IAP抑制的半胱天冬酶。 本发明还提供了一种去抑制IAP抑制的半胱天冬酶的方法。

公开(公告)号：US20060258581A1

公开(公告)日：2006-11-16

申请号：US11251617

申请日：2005-10-14

Applicant: John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

Inventor： John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

IPC: A61K38/54

CPC classification number: A61K31/337 ,  A61K31/17 ,  A61K31/704 ,  A61K31/7048 ,  A61K38/1761 ,  A61K45/06 ,  G01N33/573 ,  G01N2333/95 ,  G01N2500/02 ,  G01N2510/00 ,  A61K2300/00

Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, 21-24 and 48, a core structure selected from the group of TPI 759, TPI 882, TPI 914 or TPI 927; and a core structure from a library selected from TPI 1391, TPI 1349, TPI 1396, TPI 1509, TPI 1540, TPI 1400, TPI 792, TPI 1332, TPI 1567, TPI 1576 and TPI 1577, wherein the agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase.

Abstract translation: 本发明提供了具有选自核心肽5至39和42至55的核心肽的分离的试剂，其中所述试剂减阻IAP抑制的半胱天冬酶。 还提供了一种隔离剂，其具有选自图1和图2所示的任何结构的芯结构。 5,9,10,14B，21-24和48，选自TPI 759，TPI 882，TPI 914或TPI 927的核心结构; 和来自选自TPI1391，TPI1349，TPI1396，TPI1509，TPI1540，TPI1400，TPI792，TPI1332，TPI1567，TPI1576和TPI1577的文库的核心结构，其中所述试剂去抑制IAP抑制 半胱天冬酶 本发明还提供了一种去抑制IAP抑制的半胱天冬酶的方法。

公开(公告)号：US20070003535A1

公开(公告)日：2007-01-04

申请号：US11084714

申请日：2005-03-17

Applicant: John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

Inventor： John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

IPC: A61K38/54 ,  G01N33/574 ,  C07H21/04 ,  C12N9/99 ,  C07K16/40

CPC classification number: C07D207/09 ,  A61K38/00

Abstract: The invention provides isolated agents having novel chemical structures and possessing superior activity as derepressors of IAP inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The invention further provides assay methods employing labeled compounds of the invention, especially fluorescent labeled compounds.

公开(公告)号：US20060211627A1

公开(公告)日：2006-09-21

申请号：US11186629

申请日：2005-07-19

Applicant: John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

Inventor： John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

IPC: A61K38/08 ,  A61K38/06

CPC classification number: C07D207/09 ,  A61K38/00

Abstract: The invention provides isolated agents having novel chemical structures and possessing superior activity as derepressors of IAP inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The invention further provides assay methods employing labeled compounds of the invention, especially fluorescent labeled compounds.

公开(公告)号：US20050159359A1

公开(公告)日：2005-07-21

申请号：US11021517

申请日：2004-12-23

Applicant: John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

Inventor： John Reed ,  Richard Houghten ,  Adel Nefzi ,  John Ostresh ,  Clemencia Pinilla ,  Kate Welsh

IPC: C12Q1/02 ,  A61K38/00 ,  A61P1/04 ,  A61P3/10 ,  A61P5/16 ,  A61P9/10 ,  A61P17/06 ,  A61P19/02 ,  A61P21/00 ,  A61P21/04 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P43/00 ,  C07K5/10 ,  C07K5/103 ,  C07K5/107 ,  C07K5/11 ,  C07K5/117 ,  C07K7/04 ,  C07K7/06 ,  C12Q1/37 ,  A61K38/52 ,  C07K14/47

CPC classification number: C07K7/06 ,  A61K38/00 ,  C07K5/1008 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1024 ,  C07K5/1027

Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24 wherein said agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The method consists of contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, the agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927. The methods of the invention also can be used for promoting apoptosis in a cell and for reducing the severity of a pathology characterized by reduced levels of apoptosis. Methods for identifying agents that derepress an IAP-inhibited caspase are also provided.

Abstract translation: 本发明提供了具有选自核心肽5至39和42至55的核心肽的分离的试剂，其中所述试剂减阻IAP抑制的半胱天冬酶。 还提供了一种隔离剂，其具有选自图1和图2所示的任何结构的芯结构。 5,9,10,14B和21-24，其中所述药物抑制IAP抑制的半胱天冬酶。 本发明还提供了一种去抑制IAP抑制的半胱天冬酶的方法。 该方法包括使IAP抑制的半胱天冬酶与有效量的试剂接触以对抑制IAP-抑制的半胱天冬酶进行脱保护，该试剂具有选自核心肽的核心基序，所述核心基序具有核心肽 4至39和42至55，以及选自TPI759，TPI882，TPI914或TPI927的核心结构。 本发明的方法还可用于促进细胞凋亡和降低以凋亡水平降低为特征的病理学的严重性。 还提供了用于鉴定抑制IAP抑制的半胱天冬酶的药剂的方法。