[EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS D'HISTONE-DÉSACÉTYLASES
申请人:BROAD INST INC
公开号:WO2014018979A1
公开(公告)日:2014-01-30
The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X1, X2, X3, X4, X5, W1, W2, W3, and W4 are as described. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting β-cells and improving insulin resistence. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals.
本发明涉及式(I)的化合物或其药学上可接受的盐、水合物、溶剂合物或前药,其中X1、X2、X3、X4、X5、W1、W2、W3和W4如所述。本发明一般涉及组织脱乙酰化酶抑制剂以及制备和使用它们的方法。在一个方面,该发明涉及选择性HDAC3抑制剂,可用于保护β细胞并改善胰岛素抵抗。选择性HDAC3抑制剂还可用于促进认知功能,增强学习和记忆形成。本发明的化合物可用于治疗、缓解和/或预防各种疾病,例如代谢紊乱,如1型或2型糖尿病、血脂异常、脂肪萎缩、与代谢综合征相关的肝病、多囊卵巢综合征或肥胖症;炎症性疾病;神经系统疾病;记忆或认知功能障碍;消除学习障碍;真菌疾病或感染;病毒性疾病或感染,如艾滋病病毒;血液病;肝病;溶酶体贮积病;或人类或动物的肿瘤性疾病。