公开(公告)号：US20080200411A1

公开(公告)日：2008-08-21

申请号：US11749629

申请日：2007-05-16

申请人： Nicholas BARDEN ,  Inge Sillaber ,  Marcelo Paez-Pereda

发明人： Nicholas BARDEN ,  Inge Sillaber ,  Marcelo Paez-Pereda

IPC分类号： A61K48/00 ,  A61K38/17 ,  A61K39/395 ,  C07K16/28 ,  C07K14/705 ,  C12Q1/68 ,  C07H21/04

CPC分类号： C12Q1/6883 ,  A61K31/40 ,  A61K31/7088 ,  C07K14/705 ,  C12Q2600/156 ,  G01N33/6872 ,  G01N33/6896 ,  G01N2800/304

摘要： Nucleic acid molecules encoding an ATP-gated ion channel P2X7R which contains a mutation or a deletion are disclosed. Polypeptides encoded by the nucleic acid molecules and antibodies that specifically are directed to these polypeptides are disclosed. Aptamers that specifically bind the nucleic acid molecules, and primers for selectively amplifying the nucleic acid molecules are provided, kits, compositions, particularly pharmaceutical and diagnostic compositions comprising the nucleic acid molecules, vectors, polypeptides, aptamers, antibodies and/or primers, are provided. Methods for diagnosing affective disorders associated with a non-functional P2X7R protein, an altered ATP-gating of the P2X7R protein, an over or underexpression of the P2X7R protein or associated with the presence of any one of the nucleic acid molecules or polypeptides encoded thereby are disclosed. Additionally, the present invention relates to uses and methods for treating affective disorders employing a functional or non-functional ATP-gated ion-channel P2X7R, such as treatment with modulators of P2X7R activity.

摘要翻译： 公开了编码含有突变或缺失的ATP门控离子通道P2X7R的核酸分子。 公开了由核酸分子编码的多肽和特异性针对这些多肽的抗体。 提供了特异性结合核酸分子的选择剂和用于选择性扩增核酸分子的引物，提供试剂盒，组合物，特别是包含核酸分子，载体，多肽，适体，抗体和/或引物的药物和诊断组合物 。 用于诊断与非功能P2X7R蛋白相关的情感障碍，P2X7R蛋白的改变的ATP门控，P2X7R蛋白的过表达或低表达或与其编码的任何一种核酸分子或多肽相关联的方法， 披露 另外，本发明涉及使用功能性或非功能性ATP门控离子通道P2X7R来治疗情感障碍的用途和方法，例如用P2X7R活性的调节剂治疗。

公开(公告)号：US20130197046A1

公开(公告)日：2013-08-01

申请号：US13556988

申请日：2012-07-24

申请人： Michael Bös

发明人： Michael Bös

IPC分类号： A61K31/404 ,  A61K31/41

CPC分类号： A61K31/404 ,  A61K31/41 ,  C07D209/42 ,  C07D231/56 ,  C07D403/06 ,  C07D471/04

摘要： The present application is directed to novel P2X7R antagonists that are indol-3-carboxamide or azaindole-3-carboxamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.

公开(公告)号：US20100069463A1

公开(公告)日：2010-03-18

申请号：US12278023

申请日：2007-02-07

申请人： Marcelo Paez-Pereda ,  Marta Labeur

发明人： Marcelo Paez-Pereda ,  Marta Labeur

IPC分类号： A61K31/7088 ,  G01N33/53 ,  G01N33/566 ,  C12Q1/68

CPC分类号： G01N33/5038 ,  G01N33/5041 ,  G01N2333/72 ,  G01N2333/726 ,  G01N2800/301 ,  G01N2800/302 ,  G01N2800/304

摘要： The present invention relates to a method for identifying a TMEFF2 modulator, comprising (a) contacting a cell which expresses TMEFF2 with a candidate compound to be tested; (b) measuring whether said compound to be tested decreases or increases the level of a constituent of the cAMP signalling pathway, preferably the CRH signalling pathway, in said cell when compared to a corresponding cell which does not express TMEFF2; (b′) optionally determining whether said compound is capable of reduncing the binding between Activin and TMEFF2; and (c) identifying said modulator compound. Furthermore, a method for identifying a TMEFF2 modulator comprising determining whether said TMEFF2 modulator is capable of reducing the binding between Activin and TMEFF2 is contemplated. It also relates to uses and methods applying a TMEFF2 agonist for the treatment of Cushing's Syndromes and a TMEFF2 modulator for the treatment of affective disorders. Furthermore, methods of diagnosing affective disorders or Cushing's Syndromes are provided.

摘要翻译： 本发明涉及鉴定TMEFF2调节剂的方法，其包括（a）使表达TMEFF2的细胞与待测试的候选化合物接触; （b）当与不表达TMEFF2的相应细胞相比时，测量所述待测化合物是否降低或增加所述细胞中cAMP信号传导途径（优选CRH信号传导途径）的成分的水平; （b'）任选地确定所述化合物是否能够重新激活激活素和TMEFF2之间的结合; 和（c）鉴定所述调节剂化合物。 此外，考虑了用于鉴定TMEFF2调节剂的方法，其包括确定所述TMEFF2调节剂是否能够降低活化素和TMEFF2之间的结合。 它还涉及应用TMEFF2激动剂治疗库兴综合征和用于治疗情感障碍的TMEFF2调节剂的用途和方法。 此外，提供了诊断情感障碍或库兴氏综合征的方法。

公开(公告)号：US08569334B2

公开(公告)日：2013-10-29

申请号：US13549077

申请日：2012-07-13

申请人： Michael Bös

发明人： Michael Bös

IPC分类号： A61K31/44 ,  C07D209/42

CPC分类号： C07D209/42 ,  C07D231/56 ,  C07D403/06 ,  C07D471/04

摘要： The present application is directed to novel P2X7R antagonists that are indol-3-carboxamide or azaindole-3-carboxamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.

摘要翻译： 本申请涉及作为吲哚-3-甲酰胺或氮杂吲哚-3-甲酰胺化合物的新型P2X7R拮抗剂，包含其的药物组合物及其用于预防或治疗P2X7R活性介导的疾病的用途。

公开(公告)号：US20100267762A1

公开(公告)日：2010-10-21

申请号：US12758557

申请日：2010-04-12

申请人： MICHAEL BOES

发明人： MICHAEL BOES

IPC分类号： A61K31/437 ,  A61K31/4045 ,  C07D471/04 ,  C07D209/40 ,  A61P25/22 ,  A61P25/18 ,  A61P25/24

CPC分类号： C07D209/40

摘要： The present application is directed to novel P2X7R antagonists that are N-indol-3-yl-acetamide and N-azaindol-3-yl-acetamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.

摘要翻译： 本申请涉及作为N-吲哚-3-基 - 乙酰胺和N-氮杂吲哚-3-基 - 乙酰胺化合物的新型P2X7R拮抗剂，其包含其的药物组合物及其用于预防或治疗性治疗由 P2X7R活性。

公开(公告)号：US20060110385A1

公开(公告)日：2006-05-25

申请号：US10553298

申请日：2004-04-16

申请人： Nicholas Barden ,  Inge Sillaber ,  Marcelo Paez-Pereda

发明人： Nicholas Barden ,  Inge Sillaber ,  Marcelo Paez-Pereda

IPC分类号： C12Q1/68 ,  C07H21/04 ,  A61K39/395 ,  C07K14/705 ,  C07K16/28

CPC分类号： C12Q1/6883 ,  A61K31/40 ,  A61K31/7088 ,  C07K14/705 ,  C12Q2600/156 ,  G01N33/6872 ,  G01N33/6896 ,  G01N2800/304

摘要： The present invention relates to nucleic acid molecules, preferably genomic sequences, encoding an ATP-gated ion channel P2X7R which contain a mutation in the 5′UTR or 3′UTR regions, a mutation in exon 3, 5, 6, 8 or 13 or in introns 1, 3, 4, 5, 6, 7, 9, 11 or 12 or a deletion in exon 13, which allow to diagnose affective disorders. The invention further relates to polypeptides encoded by said nucleic acid molecules vectors and host cells comprising said nucleic acid molecules as well as to methods for producing polypeptides encoded by said nucleic acid molecules. The present invention also provides antibodies specifically directed to polypeptides encoded by said nucleic acid molecules and aptamers specifically binding said nucleic acid molecules. Additionally, primers for selectively amplifying said nucleic acid molecules are provided in the present invention as well as kits, compositions, particularly pharmaceutical and diagnostic compositions comprising said nucleic acid molecules, vectors, polypeptides, aptamers, antibodies and/or primers. Moreover, the present invention relates to methods for diagnosing affective disorders associated with a nonfunctional P2X7R protein, an altered ATP-gating of the P2X7R protein, an over- or underexpression of the P2X7R protein or associated with the presence of any one of the aforementioned nucleic acid molecules or polypeptides encoded thereby. Additionally, the present invention relates to uses and methods for treating affective disorders employing a functional or non-functional ATP-gated ion-channel P2X7R. The present invention also relates to uses of modulators of P2X7R activity for treating affective diseases. Furthermore, the present invention also relates to methods for identifying and characterizing compounds which are capable of specifically interacting with or altering the characteristics of the polypeptides of the present invention as well as to methods for the production of pharmaceutical compositions.

公开(公告)号：US08815892B2

公开(公告)日：2014-08-26

申请号：US13556988

申请日：2012-07-24

申请人： Michael Bös

发明人： Michael Bös

IPC分类号： A61K31/44

CPC分类号： A61K31/404 ,  A61K31/41 ,  C07D209/42 ,  C07D231/56 ,  C07D403/06 ,  C07D471/04

摘要： The present application is directed to novel P2X7R antagonists that are indol-3-carboxamide or azaindole-3-carboxamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.

摘要翻译： 本申请涉及作为吲哚-3-甲酰胺或氮杂吲哚-3-甲酰胺化合物的新型P2X7R拮抗剂，包含其的药物组合物及其用于预防或治疗P2X7R活性介导的疾病的用途。

公开(公告)号：US20130060047A1

公开(公告)日：2013-03-07

申请号：US13697666

申请日：2011-03-04

申请人： Michael Bos

发明人： Michael Bos

IPC分类号： C07D209/40 ,  C07D209/14

CPC分类号： C07D209/40 ,  C07D209/14

摘要： Disclosed are novel methods for the synthesis of N-substituted indol-3-yl-alkylamide compounds which act as P2X7R antagonists, said methods involving the rearrangement of an oxime intermediate.

摘要翻译： 公开了用作合成作为P2X7R拮抗剂的N-取代的吲哚-3-基 - 烷基酰胺化合物的新方法，所述方法涉及肟中间体的重排。

公开(公告)号：US07919503B2

公开(公告)日：2011-04-05

申请号：US12758557

申请日：2010-04-12

申请人： Michael Boes

发明人： Michael Boes

IPC分类号： A61K31/437 ,  A61K31/404 ,  C07D221/00 ,  C07D209/00

CPC分类号： C07D209/40

摘要： The present application is directed to novel P2X7R antagonists that are N-indol-3-yl-acetamide and N-azaindol-3-yl-acetamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.

摘要翻译： 本申请涉及作为N-吲哚-3-基 - 乙酰胺和N-氮杂吲哚-3-基 - 乙酰胺化合物的新型P2X7R拮抗剂，其包含其的药物组合物及其用于预防或治疗性治疗由 P2X7R活性。

公开(公告)号：US20090312366A1

公开(公告)日：2009-12-17

申请号：US12411090

申请日：2009-03-25

申请人： Michael Bös

发明人： Michael Bös

IPC分类号： A61K31/404 ,  C07D209/42 ,  C07D231/56 ,  C07D471/04 ,  C07D403/06 ,  A61K31/416 ,  A61K31/437 ,  A61K31/41 ,  A61P25/00

CPC分类号： C07D209/42 ,  C07D231/56 ,  C07D403/06 ,  C07D471/04

摘要： The present application is directed to novel P2X7R antagonists that are indol-3-carboxamide or azaindole-3-carboxamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.

摘要翻译： 本申请涉及作为吲哚-3-甲酰胺或氮杂吲哚-3-甲酰胺化合物的新型P2X7R拮抗剂，包含其的药物组合物及其用于预防或治疗P2X7R活性介导的疾病的用途。