651311-01-2Relevant academic research and scientific papers
Structure activity relationship studies of 3-arylsulfonyl-pyrido[1,2-a] pyrimidin-4-imines as potent 5-HT6 antagonists
Hu, Shuanghua,Huang, Yazhong,Wu, Yong-Jin,He, Huan,Grant-Young, Katherine A.,Bertekap, Robert L.,Whiterock, Valerie,Brassil, Patrick,Lentz, Kimberley,Sivaprakasam, Prasanna,Langley, David R.,Westphal, Ryan S.,Scola, Paul M.
, p. 1782 - 1790 (2014/03/21)
Comprehensive structure activity relationship (SAR) studies were conducted on a focused screening hit, 2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a] pyrimidin-4-imine (1, IC50: 4.0 nM), as 5-HT6 selective antagonists. Activity was improved some 2-4 fold when small, electron-donating groups were added to the central core as observed in 19, 20 and 26. Molecular docking of key compounds in a homology model of the human 5-HT6 receptor was used to rationalize our structure-activity relationship (SAR) findings. In pharmacokinetic experiments, compound 1 displayed good brain uptake in rats following intra-peritoneal administration, but limited oral bioavailability.
Pyridopyrimidine derivatives as 5-HT6 antagonists
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Page/Page column 12, (2010/02/05)
Novel pyridopyrimidine derivatives which have a binding affinity for the human 5-HT6 receptor and, therefore, are useful in treating disorders responsive to antagonism of the 5-HT6 receptor such as psychosis, schizophrenia, manic depression, depression, neurological disorder, memory disorder, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's chorea.
