| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1378683 | Bioorganic & Medicinal Chemistry Letters | 2006 | 6 Pages |
Abstract
Recently, we reported potent and small-sized β-secretase (BACE1) inhibitors KMI-570 and KMI-684 in which we replaced carboxylic acid groups at the P1′ position of KMI-420 and KMI-429, respectively, with tetrazole derivatives as carboxylic acid bioisosteres. These modifications improved significantly BACE1 inhibitory activity and chemical stability. In this study, the acidic tetrazole ring of the P4 position of KMI-420 and KMI-570, respectively, was replaced with various hydrogen bond acceptor groups. We found BACE1 inhibitor KMI-574 that exhibited potent inhibitory activity in cultured cells as well as in vitro enzymatic assay.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Yoshio Hamada, Naoto Igawa, Hayato Ikari, Zyta Ziora, Jeffrey-Tri Nguyen, Abdellah Yamani, Koushi Hidaka, Tooru Kimura, Kazuki Saito, Yoshio Hayashi, Maiko Ebina, Shoichi Ishiura, Yoshiaki Kiso,