98455-93-7Relevant academic research and scientific papers
Synthesis and evaluation of N-alkyl-S-[3-(piperidin-1-yl)propyl] isothioureas: High affinity and human/rat species-selective histamine H 3 receptor antagonists
Harusawa, Shinya,Sawada, Koichi,Magata, Takuji,Yoneyama, Hiroki,Araki, Lisa,Usami, Yoshihide,Hatano, Kouta,Yamamoto, Kouichi,Yamamoto, Daisuke,Yamatodani, Atsushi
, p. 6415 - 6420 (2013/11/19)
S-Alkyl-N-alkylisothiourea compounds containing various cyclic amines were synthesized in the search for novel nonimidazole histamine H3 receptor (H3R) antagonists. Among them, four N-alkyl S-[3-(piperidin-1-yl)propyl]isothioureas 18, 19, 22, and 23 were found to exhibit potent and selective H3R antagonistic activities against in vitro human H3R, but were inactive against in vitro human H 4R. Furthermore, three alkyl homologs 18-20 showed inactivity for histamine release in in vivo rat brain microdialysis, suggesting differences in antagonist affinities between species. In addition, in silico docking studies of N-[4-(4-chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea 19 and a shorter homolog 17 with human/rat H3Rs revealed that structural differences between the antagonist-docking cavities of rat and human H 3Rs were likely caused by the Ala122/Val122 mutation.
