18694-14-9Relevant academic research and scientific papers
Chemical modifications of the N-methyl-laudanosine scaffold point to new directions for SK channels exploration
Badarau, Eduard,Dilly, Sbastien,Wouters, Johan,Seutin, Vincent,Ligeois, Jean-Franois
supporting information, p. 5616 - 5620 (2015/01/08)
An asparagine or a histidine are present in a similar position in the outer pore region of SK2 and SK3 channels, respectively. Therefore, this structural difference was targeted in order to develop selective blockers of SK channel subtypes. Following docking investigations, based on theoretical models of truncated SK2 and SK3 channels, the benzyl side chain of N-methyl-laudanosine (NML) was functionalized in order to target this specific amino-acid residues. Chiral butanamide and benzyloxy analogues were prepared, resolved and tested for their affinity for SK2 and SK3 channels. Isoquinolinium (NMIQ) derivatives have a higher affinity for both SK channel subtypes than the corresponding derivative with no functionalized side chain. This trend was observed also for the 1,2,3,4-tetrahydroisoquinoline (THIQ) analogues. A benzyloxy functionalized NML enantiomer has a higher affinity than NML stereoisomers. Otherwise, the conserved affinity of these analogues led to the opportunity to further investigate in terms of possible labeling for in vivo investigations of the role of SK channels.
Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A
Zhang, Zhanbin,Lu, Xiaoxia,Xu, Jinbin,Rothfuss, Justin,MacH, Robert H.,Tu, Zhude
, p. 3986 - 3995 (2011/10/31)
A series of analogues were synthesized by optimizing the structure of papaverine. The in vitro PDE10A binding affinity (IC50) values for these new analogues were measured; for compounds that have IC50 value less than 60 nM for PDE10A
