1292318-19-4Relevant academic research and scientific papers
Structure-activity relationship investigation of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors
Ngo, Van T.H.,Hoang, Van-Hai,Tran, Phuong-Thao,Van Manh, Nguyen,Ann, Jihyae,Kim, Eunhye,Cui, Minghua,Choi, Sun,Lee, Jiyoun,Kim, Hee,Ha, Hee-Jin,Choi, Kwanghyun,Kim, Young-Ho,Lee, Jeewoo
, p. 3133 - 3144 (2018)
Glutamyl cyclase (QC) is a promising therapeutic target because of its involvement in the pathogenesis of Alzheimer's disease. In this study, we developed novel QC inhibitors that contain 3-aminoalkyloxy-4-methoxyphenyl and 4-aminoalkyloxyphenyl groups to replace the previously developed pharmacophore. Several potent inhibitors were identified, showing IC50 values in a low nanomolar range, and were further studied for in vitro toxicity and in vivo activity. Among these, inhibitors 51 and 53 displayed the most potent AβN3pE?40-lowering effects in in vivo acute model with reasonable BBB penetration, without showing cytotoxicity and hERG inhibition. The molecular modeling analysis of 53 indicated that the salt bridge interaction and the hydrogen bonding in the active site provided a high potency. Given the potent activity and favorable BBB penetration with low cytotoxicity, we believe that compound 53 may serve as a potential candidate for anti-Alzheimer's agents.
AMINO - PYRIMIDINE COMPOUNDS AS INHIBITORS OF TBK1 AND/OR IKK EPSILON
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Page/Page column 129; 130, (2011/05/05)
The invention relates to certain aminopyrimidine compounds which inhibit TBK1 and/or IKK epsilon and which may therefore find application in treating inflammation, cancer, septic shock and/or Primary open Angle Glaucoma (POAG).
