Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson¡¯s disease model
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- 作者：Abhisek Banerjee ; S ; ip Patil ; Mahesh Y. Pawar ; Srinivas Gullapalli ; Praveen K. Gupta ; Maulik N. G ; hi ; Deepak K. Bhateja ; Malini Bajpai ; Ramach ; ra Rao Sangana ; Girish S. Gudi ; Neelima Khairatkar-Joshi ; Laxmikant A. Gharat
- 关键词：PDE7 ; Imidazopyridazinone ; CNS penetration ; Parkinson&rsquo ; s disease ; MPTP ; Haloperidol
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：1 October, 2012
- 年：2012
- 卷：22
- 期：19
- 页码：6286-6291
- 全文大小：2377 K
文摘
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.