新型N-1取代吡唑并嘧啶酮作为强效、选择性磷酸二酯酶2抑制剂的发现。
Discovery of novel N-1 substituted pyrazolopyrimidinones as potent, selective PDE2 inhibitors.
作者信息
Morriello Gregori J, Dwyer Michael P, Chen Yili, Ginetti Anthony T, Xu Shimin, Lu Jun, Abeywickrema Pravien, Wang Deping, Crespo Alejandro, Cabalu Tamara D, Wilson Jonathan E, Stachel Shawn J, Paone Daniel V, Sinz Christopher
机构信息
Discovery Chemistry, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
Discovery Chemistry, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.
出版信息
Bioorg Med Chem Lett. 2021 Jul 15;44:128082. doi: 10.1016/j.bmcl.2021.128082. Epub 2021 May 13.
A focused SAR study was conducted on a series of N1-substituted pyrazolopyrimidinone PDE2 inhibitors to reveal compounds with excellent potency and selectivity. The series was derived from previously identified internal leads and designed to enhance steric interactions with key amino acids in the PDE2 binding pocket. Compound 26 was identified as a lead compound with excellent PDE2 selectivity and good physicochemical properties.
对一系列N1-取代的吡唑并嘧啶酮PDE2抑制剂进行了针对性的SAR研究，以发现具有优异效力和选择性的化合物。该系列化合物源自先前确定的内部先导物，旨在增强与PDE2结合口袋中关键氨基酸的空间相互作用。化合物26被鉴定为具有优异PDE2选择性和良好物理化学性质的先导化合物。
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