二氢咪唑并异喹啉衍生物作为磷酸二酯酶 10A 抑制剂用于治疗精神分裂症的 SAR 研究。
The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia.
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, United States.
出版信息
Bioorg Med Chem Lett. 2012 Apr 1;22(7):2585-9. doi: 10.1016/j.bmcl.2012.01.113. Epub 2012 Feb 9.
The identification of potent and orally active dihydroimidazoisoquinolines as PDE 10A inhibitors is reported. The SAR development led to the discovery of compound 35 as a potent, selective, and orally active PDE10A inhibitor. Compound 35 inhibited MK-801-induced hyperactivity at 3mg/kg and displayed a 10-fold separation between the minimal effective doses for inhibition of MK-801-induced hyperactivity and hypolocomotion in rats.
报告了具有强效和口服活性的二氢咪唑并异喹啉作为 PDE10A 抑制剂的鉴定。通过 SAR 研究发现了化合物 35，它是一种强效、选择性和口服活性的 PDE10A 抑制剂。化合物 35 在 3mg/kg 时抑制 MK-801 诱导的过度活动，并在抑制 MK-801 诱导的过度活动和大鼠的低活动剂量之间表现出 10 倍的分离。
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