- Design and optimization of purine derivatives as in vivo active PDE10A inhibitors
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Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target. Based on the structural similarity between our previous chemistry work on 8-aminoimidazo[1,2-a]pyrazines and the PDE10A inhibitors reported by Bartolome-Nebreda et al., we initialized a project for developing PDE10A inhibitors. After several rounds of optimization, we were able to obtain a few compounds with good PDE10A enzymatic activity. And after further PDE enzymatic selectivity study, metabolic stability assay and in vivo pharmacological tests we identified two inhibitors as interesting lead compounds with the potential for further PDE10A lead optimizatioin.
- Chen, Liu,Chen, Danqi,Tang, Le,Ren, Jing,Chen, Jiaojiao,Zhen, Xuechu,Liu, Yu-Chih,Zhang, Chenhua,Luo, Haibin,Shen, Jingkang,Xiong, Bing
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p. 3315 - 3329
(2017/05/29)
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- COMPOSITIONS AND METHODS USING THE SAME FOR TREATMENT OF NEURODEGENERATIVE AND MITOCHONDRIAL DISEASE
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The present disclosure is directed, in part, to compounds, or pharmaceutically acceptable salts thereof, for the treatment and/or prevention of neurodegenerative disease and/or mitchonodrial disease including Parkinson's disease and Leigh's disease.
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Page/Page column 139
(2015/09/22)
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- HETEROCYCLIC COMPOUNDS AND METHODS OF USE
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Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 262
(2012/08/27)
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- Dichotomy in regioselective cross-coupling reactions of 6,8-dichloropurines with phenylboronic acid and methylmagnesium chloride: Synthesis of 6,8-di-substituted purines
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Pd-catalyzed cross-coupling reaction of 6,8-dichloro-9-(tetrahydropyran-2- yl)purine with one equivalent of phenylboronic acid proceeded regioselectively to give 8-chloro-6-phenylpurine, while the analogous Fe-catalyzed reaction with methylmagnesium chlor
- Hocek, Michal,Hockova, Dana,Dvorakova, Hana
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p. 889 - 894
(2007/10/03)
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- Specificity of the 1-Methyladenine Receptors in Starfish Oocytes: Synthesis and Properties of Some 1,8-Disubstituted Adenines, 1,6-Dimethyl-1H-purine, and of the 1-(Azidobenzyl)adenines
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A selective synthesis of 1,6-dimethylpurine (16) and the preparations of the 1-(azidobenzyl)adenines (11)-(13), 8-azido-1-benzyladenine (10), and 1-methyladenine derivatives (2)-(9) with various 8-substituents (azido, chloro, bromo, alkyl, and hydroxymeth
- Mornet, Rene,Leonard, Nelson J.,Theiler, Jane B.,Doree, Marcel
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p. 879 - 885
(2007/10/02)
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