145899-46-3Relevant articles and documents
Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1′ and P4 positions
Tagad, Harichandra D.,Hamada, Yoshio,Nguyen, Jeffrey-Tri,Hamada, Takashi,Abdel-Rahman, Hamdy,Yamani, Abdellah,Nagamine, Ayaka,Ikari, Hayato,Igawa, Naoto,Hidaka, Koushi,Sohma, Youhei,Kimura, Tooru,Kiso, Yoshiaki
experimental part, p. 3175 - 3186 (2010/07/04)
We previously reported potent BACE1 inhibitors KMI-420 and KMI-570 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Acidic moieties at the P1′ and P4 positions of KMI inhibitors are thought to be unfavorable in terms of membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P4 position with hydrogen bond accepting groups and acidic moieties at the P1′ position with less acidic and similar molecular-size moieties (carboxylic acid or tetrazole bioisosteres). These inhibitors exhibited improved BACE1 inhibitory activities and a thorough quantitative structure-activity relationship study was performed.
Design and synthesis of potent β-secretase (BACE1) inhibitors with P1′ carboxylic acid bioisosteres
Kimura, Tooru,Hamada, Yoshio,Stochaj, Monika,Ikari, Hayato,Nagamine, Ayaka,Abdel-Rahman, Hamdy,Igawa, Naoto,Hidaka, Koushi,Nguyen, Jeffrey-Tri,Saito, Kazuki,Hayashi, Yoshio,Kiso, Yoshiaki
, p. 2380 - 2386 (2007/10/03)
Recently, we reported potent and small-sized β-secretase (BACE1) inhibitors KMI-420 and KMI-429 in which we replaced the Glu residue at the P4 position of KMI-260 and KMI-360, respectively, with a 1H-tetrazole-5-carbonyl DAP (l-α,β-diaminopropi
