基于6,7-二氢-5H-吡咯并[1,2-a]咪唑支架的JNK3抑制剂的神经保护作用。
The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold.
作者信息
Graczyk Piotr P, Khan Afzal, Bhatia Gurpreet S, Palmer Vanessa, Medland Darren, Numata Hirotoshi, Oinuma Hitoshi, Catchick Jacqueline, Dunne Angela, Ellis Moira, Smales Caroline, Whitfield Jonathan, Neame Stephen J, Shah Bina, Wilton Daniel, Morgan Louise, Patel Toshal, Chung Raymond, Desmond Howard, Staddon James M, Sato Nobuaki, Inoue Atsushi
机构信息
Eisai London Research Laboratories, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK.
出版信息
Bioorg Med Chem Lett. 2005 Nov 1;15(21):4666-70. doi: 10.1016/j.bmcl.2005.07.076.
Imidazole-based structures of p38 inhibitors served as a starting point for the design of JNK3 inhibitors. Construction of a 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold led to the synthesis of the (S)-enantiomers, which exhibited p38/JNK3 IC50 ratio of up to 10 and were up to 20 times more potent inhibitors of JNK3 than the relevant (R)-enantiomers. The JNK3 inhibitory potency correlated well with inhibition of c-Jun phosphorylation and neuroprotective properties of the compounds in low K+-induced cell death of rat cerebellar granule neurones.
基于咪唑的p38抑制剂结构是设计JNK3抑制剂的起点。构建6,7-二氢-5H-吡咯并[1,2-a]咪唑支架导致了（S）-对映体的合成，其p38/JNK3 IC50比值高达10，并且作为JNK3抑制剂的效力比相关的（R）-对映体高20倍。JNK3抑制效力与化合物在低K +诱导的大鼠小脑颗粒神经元细胞死亡中对c-Jun磷酸化的抑制和神经保护特性密切相关。
Zotero 插件