METHODS FOR THE IDENTIFICATION OF ZAP-70 INTERACTING MOLECULES AND FOR THE PURIFICATION OF ZAP-70

    公开(公告)号:US20120178180A1

    公开(公告)日:2012-07-12

    申请号:US12302711

    申请日:2007-06-01

    IPC分类号: G01N33/53 G01N30/02

    摘要: The invention provides in a first aspect a method for the identification of an ZAP-70 interacting compound, comprising the steps of a) providing a protein preparation containing phosphorylated ZAP-70, b) contacting the protein preparation with aminopyrido-pyrimidine ligand 24 immobilized on a solid support under conditions allowing the formation of an aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex, c) incubating the aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex with a given compound, and d) determining whether the compound is able to separate phosphorylated ZAP-70 from the immobilized aminopyrido-pyrimidine ligand 24. In a second aspect, the present invention relates to A method for the identification of an ZAP-70 interacting compound, comprising the steps of a) providing a protein preparation containing phosphorylated ZAP-70, b) contacting the protein preparation with ligand aminopyrido-pyrimidine ligand 24 immobilized on a solid support and with a given compound under conditions allowing the formation of an aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex, and c) detecting the aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex formed in step b). In a third aspect, the invention provides a method for the identification of an ZAP-70 interacting compound, comprising the steps of: a) providing two aliquots of a protein preparation containing phosphorylated ZAP-70, b) contacting one aliquot with aminopyrido-pyrimidine ligand 24 immobilized on a solid support under conditions allowing the formation of an aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex, c) contacting the other aliquot with aminopyrido-pyrimidine ligand 24 immobilized on a solid support and with a given compound under conditions allowing the formation of an aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex, and d) determining the amount of aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex formed in steps b) and c). In a forth aspect, the invention relates to a method for the identification of an ZAP-70 interacting compound, comprising the steps of: a) providing two aliquots comprising each at least one cell containing phosphorylated ZAP-70, b) incubating one aliquot with a given compound, c) harvesting the cells of each aliquot, d) lysing the cells in order to obtain protein preparations, e) contacting the protein preparations with aminopyrido-pyrimidine ligand 24 immobilized on a solid support under conditions allowing the formation of an aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex, and f) determining the amount of aminopyrido-pyrimidine ligand 24—phosphorylated ZAP-70 complex formed in each aliquot in step e).

    PYRIMIDINE DERIVATIVES AS ZAP-70 INHIBITORS
    6.
    发明申请
    PYRIMIDINE DERIVATIVES AS ZAP-70 INHIBITORS 审中-公开
    吡嗪衍生物作为ZAP-70抑制剂

    公开(公告)号:US20120142667A1

    公开(公告)日:2012-06-07

    申请号:US13377550

    申请日:2010-06-10

    CPC分类号: C07D239/48

    摘要: The invention relates to compounds of formula (I) wherein R1 to R5, X and X1 to X3 have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of ZAP-70 for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

    摘要翻译: 本发明涉及式(I)化合物,其中R 1至R 5,X和X 1至X 3具有如在说明书和权利要求书中引用的含义。 所述化合物可用作ZAP-70的抑制剂,用于治疗或预防免疫学,炎性,自身免疫性,过敏性疾病和免疫介导的疾病。 本发明还涉及包含所述化合物的药物组合物,这些化合物的制备以及作为药物的用途。

    ORTHO SUBSTITUTED PYRIMIDINE COMPOUNDS AS JAK INHIBITORS
    10.
    发明申请
    ORTHO SUBSTITUTED PYRIMIDINE COMPOUNDS AS JAK INHIBITORS 审中-公开
    ORTHO替代吡嗪化合物作为JAK抑制剂

    公开(公告)号:US20120172385A1

    公开(公告)日:2012-07-05

    申请号:US13394575

    申请日:2010-09-07

    CPC分类号: C07D403/12 C07D239/48

    摘要: The invention relates to compounds of formula (I) wherein X1 to X3, R, R2 to R7 and AA have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

    摘要翻译: 本发明涉及式(I)的化合物,其中X 1至X 3,R 2,R 2至R 7和AA具有在说明书和权利要求书中引用的含义。 所述化合物可用作JAK抑制剂,用于治疗或预防免疫学,炎症,自身免疫,过敏性疾病和免疫介导的疾病。 本发明还涉及包含所述化合物的药物组合物,这些化合物的制备以及作为药物的用途。