Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson's disease model

被引：31

作者：

Banerjee, Abhisek ^{[1
]}

Patil, Sandip ^{[1
]}

Pawar, Mahesh Y. ^{[1
]}

Gullapalli, Srinivas ^{[1
]}

Gupta, Praveen K. ^{[1
]}

Gandhi, Maulik N. ^{[1
]}

Bhateja, Deepak K. ^{[1
]}

Bajpai, Malini ^{[1
]}

Sangana, Ramachandra Rao ^{[1
]}

Gudi, Girish S. ^{[1
]}

Khairatkar-Joshi, Neelima ^{[1
]}

Gharat, Laxmikant A. ^{[1
]}

机构：

[1] Glenmark Pharmaceut Ltd, Navi Mumbai 400709, Maharashtra, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 19期

关键词：

PDE7; Imidazopyridazinone; CNS penetration; Parkinson's disease; MPTP; Haloperidol; CAMP-SPECIFIC PHOSPHODIESTERASE; RAT STRIATUM; DISORDERS; MICE; HALOPERIDOL; EFFICACY; ROLIPRAM;

D O I：

10.1016/j.bmcl.2012.07.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：6286 / 6291

页数：6

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