Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson's disease model
Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson's disease model
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DOI：
10.1016/j.bmcl.2012.07.077
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发表时间：
2012-10-01
影响因子：
2.7
通讯作者：
Gharat, Laxmikant A.
中科院分区：
文献类型：
--
作者：
Banerjee, Abhisek;Patil, Sandip;Gharat, Laxmikant A.
公开了一系列来自咪唑并哒嗪酮支架的化合物作为 PDE7 抑制剂的合成和构效关系研究。鉴定出有效的类似物，例如化合物 7 (31 nM)、8 (27 nM) 和 9 (12 nM)。还公开了化合物 7、8 和 9 的 PDE 选择性和药代动力学特征。化合物7在小鼠体内的中枢神经系统充分渗透，使其能够在MPTP诱导的PD模型和氟哌啶醇诱导的僵直模型中进行测试，以探讨PDE7在纹状体通路中的差异药理学。 (C) 2012 Elsevier Ltd. 保留所有权利。
The synthesis and structure-activity relationship studies of a series of compounds from imidazopyridazinone scaffold as PDE7 inhibitors are disclosed. Potent analogs such as compounds 7 (31 nM), 8 (27 nM), and 9 (12 nM) were identified. The PDE selectivity and pharmacokinetic profile of compounds 7, 8 and 9 are also disclosed. The adequate CNS penetration of compound 7 in mice allowed it to be tested in the MPTP induced PD model and haloperidol induced catalepsy model to probe the differential pharmacology of PDE7 in the striatal pathway. (C) 2012 Elsevier Ltd. All rights reserved.