Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors was written by Ding, Xiao;Stasi, Luigi Piero;Ho, Ming-Hsun;Zhao, Baowei;Wang, Hailong;Long, Kai;Xu, Qiongfeng;Sang, Yingxia;Sun, Changhui;Hu, Huan;Yu, Haihua;Wan, Zehong;Wang, Lizhen;Edge, Colin;Liu, Qian;Li, Yi;Dong, Kelly;Guan, Xiaoming;Tattersall, F. David;Reith, Alastair D.;Ren, Feng. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2018.Product Details of 93643-24-4 This article mentions the following:
Inhibition of LRRK2 kinase activity with small mols. has emerged as a potential novel therapeutic treatment for Parkinson’s disease. Herein the authors disclose the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent LRRK2 inhibitors identified through a kinase-focused set screening. Optimization of the physicochem. properties and kinase selectivity led to the discovery of compound 7 ((4-((4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone), which exhibited potent in vitro inhibition of LRRK2 kinase activity, good physicochem. properties and kinase selectivity across the kinome. Moreover, compound 7 was able to penetrate into the CNS, and in vivo pharmacol. studies revealed significant inhibition of Ser 935 phosphorylation in the brain of both rats (30 and 100 mg/kg) and mice (45 mg/kg) following oral administration. In the experiment, the researchers used many compounds, for example, (S)-1,4-Diazabicyclo[4.3.0]nonane (cas: 93643-24-4Product Details of 93643-24-4).
(S)-1,4-Diazabicyclo[4.3.0]nonane (cas: 93643-24-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Product Details of 93643-24-4
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics