[EN] NONMUSCLE MYOSIN II INHIBITORS FOR SUBSTANCE USE RELAPSE<br/>[FR] INHIBITEURS DE MYOSINE NON MUSCULAIRE II POUR LA RECHUTE D'UTILISATION DE SUBSTANCE
申请人:SCRIPPS RESEARCH INST
公开号:WO2019241469A1
公开(公告)日:2019-12-19
The invention can provide compounds, analogs of blebbistatin, effective and selective inhibitors of nonmuscle myosin II relative to cardiac myosin II. Compounds can be used in the method of treating a disease, disorder, or medical condition in a patient, comprising modulating myosin II ATPase, such as treatment of substance abuse relapse disorder, or of renal disease, cancer and metastasis, benign prostate hyperplasia, hemostasis or thrombosis, nerve injury including retinal damage, lung fibrosis, liver fibrosis, arthrofibrosis, wound healing, spinal cord injury, periodontitis, glaucoma and immune-related diseases including multiple sclerosis; or wherein the disease, disorder, or medical condition comprises addiction including abuse of or addiction to anything classified as a Substance-Related or Addictive Disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM), such as, but not limited to, cocaine, opioids, amphetamines, ethanol, cannabis/marijuana, nicotine, and activities including gambling Compounds are of general formula (I) with substituents as defined herein.
这项发明可以提供化合物,它们是blebbistatin的类似物,相对于心肌肌球蛋白II,是有效且选择性的非肌肌球蛋白II的抑制剂。这些化合物可以用于治疗患者的疾病、紊乱或医疗状况的方法,包括调节肌球蛋白II ATP酶,如治疗物质滥用复发紊乱、肾脏疾病、癌症和转移、良性前列腺增生、止血或血栓形成、神经损伤包括视网膜损伤、肺纤维化、肝脏纤维化、关节纤维化、伤口愈合、脊髓损伤、牙周炎、青光眼和包括多发性硬化在内的免疫相关疾病;或者该疾病、紊乱或医疗状况包括成瘾,包括对《精神障碍诊断与统计手册》(DSM)中分类为物质相关或成瘾性紊乱的任何物质的滥用或成瘾,例如,但不限于,可卡因、阿片类药物、安非他明、乙醇、大麻/大麻素、尼古丁,以及包括赌博在内的活动。这些化合物具有通用的化学式(I),其取代基如本文所定义。