公开(公告)号：US20140248268A1

公开(公告)日：2014-09-04

申请号：US14278468

申请日：2014-05-15

申请人： Angela Wandinger-Ness ,  Larry Sklar ,  Jacob Agola ,  Zurab Surviladze ,  Jeffrey Aube ,  Jennifer Golden ,  Chad E. Schroeder ,  Denise S. Simpson

发明人： Angela Wandinger-Ness ,  Larry Sklar ,  Jacob Agola ,  Zurab Surviladze ,  Jeffrey Aube ,  Jennifer Golden ,  Chad E. Schroeder ,  Denise S. Simpson

IPC分类号： C07D495/04 ,  A61K45/06 ,  A61K31/381

CPC分类号： C07D495/04 ,  A61K31/381 ,  A61K45/06

摘要： This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

摘要翻译： 本发明涉及化合物及其作为Rab7 GTPase的抑制剂或活化剂的用途，用于治疗或预防Rab 7 GTP酶相关疾病如神经病变，癌症，骨骼和脂质储存代谢疾病的发生。 本发明也适用于Rab7灭活或其蛋白质 - 蛋白质相互作用被调节以促进病原体的细胞内存活的感染性疾病。 所描述的化合物作为核苷酸结合的竞争性抑制剂，因此也可用作靶向其他小GTP酶的支架。 一方面，本发明的治疗方法用于治疗或预防遗传性感觉神经病发作，例如Charcot-Marie-Tooth 2B型疾病。 还提供了相关的药物组合物，测定和药物筛选。

公开(公告)号：US08765803B1

公开(公告)日：2014-07-01

申请号：US13404921

申请日：2012-02-24

申请人： Angela Wandinger-Ness ,  Larry Sklar ,  Jacob Agola ,  Zurab Surviladze ,  Jeffrey Aubé ,  Jennifer Golden ,  Chad E. Schroeder ,  Denise S. Simpson

发明人： Angela Wandinger-Ness ,  Larry Sklar ,  Jacob Agola ,  Zurab Surviladze ,  Jeffrey Aubé ,  Jennifer Golden ,  Chad E. Schroeder ,  Denise S. Simpson

IPC分类号： A01N43/10 ,  A01N43/16

CPC分类号： C07D495/04 ,  A61K31/381 ,  A61K45/06

摘要： This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

摘要翻译： 本发明涉及化合物及其作为Rab7 GTPase的抑制剂或活化剂的用途，用于治疗或预防Rab 7 GTP酶相关疾病如神经病变，癌症，骨骼和脂质储存代谢疾病的发生。 本发明也适用于Rab7灭活或其蛋白质 - 蛋白质相互作用被调节以促进病原体的细胞内存活的感染性疾病。 所描述的化合物作为核苷酸结合的竞争性抑制剂，因此也可用作靶向其他小GTP酶的支架。 一方面，本发明的治疗方法用于治疗或预防遗传性感觉神经病发作，例如Charcot-Marie-Tooth 2B型疾病。 还提供了相关的药物组合物，测定和药物筛选。