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    • 6. 发明申请
    • PYRIDOPYRIMIDINES FOR TREATING INFLAMMATORY AND OTHER DISEASES
    • WO2005105097A3
    • 2005-11-10
    • PCT/EP2005/051892
    • 2005-04-27
    • GPC BIOTECH AGDAUB, HenrikWISSING, JosefMISSIO, AndreaKLEBL, Bert
    • DAUB, HenrikWISSING, JosefMISSIO, AndreaKLEBL, Bert
    • A61K31/513A61P29/00A61P37/00
    • The present invention relates to the use of pyridopyrimidine derivatives having the general formula (I) wherein X represents =NH, =N-Acyl, =O, or =S; R 1 represents -NR 3 R 4 , -SR 3 , -SO-R 3 , -SO 2 -R 3 , -OR 3 ; R 2 , R 3 , and R 4 are independently of each other hydrogen, -(CH 2 ) n Ph*, heteroaryl, C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl; wherein the cycloalkyl, alkyl, alkanoyl, alkenyl, alkynyl residues can optionally substituted by one or more of the following groups: -NR 5 R 6 , phenyl, substituted phenyl, thioalkyl, alkyloxy, hydroxy, carboxy, halogen, cycloalkyl; R 5 and R 6 are independently of each other hydrogen, (CH 2 ) n Ph*, heteroaryl, C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkyl, C 1 -C 6 -alkanoyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl; R 5 and R 6 can be taken together with the nitrogen to which they are attached to complete a ring having 3 to 7 carbon atoms, optionally containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, and sulfur; Ph* represents phenyl or substituted phenyl; n is 0, 1, 2, or 3; R 4 can optionally be -CO-R 3 , -CO-OR 3 , -SO 2 -R 3 , -SO 2 -NR 5 R 6 , -CO-NR 5 R 6 , -CS-NR 5 R 6 , -C(=NH)-R 3 , -C(=NH)-NR 5 R 6 ; R 3 and R 4 can be taken together with the nitrogen to which they are attached to complete a ring having 3 to 7 carbon atoms, optionally containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, and sulfur; Ar represents phenyl, substituted phenyl, or heteroaryl; and pharmaceutically acceptable salts thereof for prophylaxis and/or treatment of inflammatory diseases, neurodegenerative disorders, immunological diseases, neuroimmunological diseases, autoimmune diseases, diabetes, transplant rejection, infective diseases, prion diseases, cardiovascular diseases and disorders.
    • 9. 发明申请
    • SUSCEPTIBILITY TO SELECTIVE CDK9 INHIBITORS
    • 选择性CDK9抑制剂的缺点
    • WO2013026890A1
    • 2013-02-28
    • PCT/EP2012/066366
    • 2012-08-22
    • LEAD DISCOVERY CENTER GMBHMAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WISSENSCHAFTEN E.V.CHOIDAS, AxelKLEBL, BertHABENBERGER, PeterEICKHOFF, JanTHOMAS, RomanHEUCKMANN, Johannes
    • CHOIDAS, AxelKLEBL, BertHABENBERGER, PeterEICKHOFF, JanTHOMAS, RomanHEUCKMANN, Johannes
    • C12Q1/68
    • G01N33/5011C12Q1/6881C12Q1/6886C12Q2600/106G01N2800/52
    • The present invention relates to a method of selecting (a) cell(s), (a) tissue(s) or (a) cell culture(s) with susceptibility to a selective CDK9 inhibitor. Also a method for determining the responsiveness of a mammalian tumor cell or cancer cell to treatment with a selective CDK9 inhibitor is described herein. In particular, the present invention provides for an in vitro method for the identification of a responder for or a patient sensitive to a selective CDK9 inhibitor, whereby the patient is suspected to suffer from NUT midline carcinoma (NMC). The present invention also relates to a method of monitoring or predicting the efficacy of a treatment of NUT midline carcinoma (NMC), wherein treatment with a selective CDK9 inhibitor is in particular envisaged. Also the use of a (transgenic) non-human animal or a (transgenic) cell having at least one rearrangement in the NUT gene for screening and/or validation of a medicament for the treatment NUT midline carcinoma (NMC) is described. Furthermore, a kit useful for carrying out the methods described herein as well as an olieo- or polynucleotide canable of detecting rearrangements in the NUT nene are provided.
    • 本发明涉及选择(a)对选择性CDK9抑制剂具有敏感性的细胞,(a)组织或(a)细胞培养物的方法。 本文还描述了确定哺乳动物肿瘤细胞或癌细胞对用选择性CDK9抑制剂进行治疗的反应性的方法。 特别地,本发明提供了用于鉴定对选择性CDK9抑制剂敏感的患者或患者的体外方法,由此患者怀疑患有NUT中线癌(NMC)。 本发明还涉及监测或预测NUT中线癌(NMC)治疗功效的方法,其中特别设想用选择性CDK9抑制剂治疗。 还描述了在NUT基因中具有至少一个重排的(转基因)非人动物或(转基因)细胞用于筛选和/或验证用于治疗NUT中线癌(NMC)的药物的用途。 此外,提供了可用于实施本文所述方法的试剂盒以及可检测NUT烯内重排的醇或多核苷酸。