Modulators of orexin receptors are being developed for neurological illnesses such as sleep disorders, addictive behaviours and other psychiatric diseases. We herein describe the discovery of CVN766, a potent orexin 1 receptor antagonist that has greater than 1000-fold selectivity for the orexin 1 receptor over the orexin 2 receptor and demonstrates low off target hits in a diversity screen. In agreement with its in vitro ADME data, CVN766 demonstrated moderate in vivo clearance in rodents and displayed good brain permeability and target occupancy. This drug candidate is currently being investigated in clinical trials for schizophrenia and related psychiatric conditions.

食欲素受体调节剂正在开发用于治疗神经系统疾病，例如睡眠障碍、成瘾行为和其他精神疾病。我们在此描述了CVN766的发现，CVN766 是一种有效的食欲素 1 受体拮抗剂，其对食欲素 1 受体的选择性比食欲素 2 受体高 1000 倍，并且在多样性筛选中表现出低脱靶命中率。与体外 ADME 数据一致，CVN766在啮齿动物体内表现出中等的体内清除率，并表现出良好的脑通透性和靶点占有率。该候选药物目前正在针对精神分裂症和相关精神疾病的临床试验中进行研究。