207447-38-9Relevant academic research and scientific papers
Small-sized human immunodeficiency virus type-1 protease inhibitors containing allophenylnorstatine to explore the s2′ pocket
Hidaka, Koushi,Kimura, Tooru,Abdel-Rahman, Hamdy M.,Nguyen, Jeffrey-Tri,McDaniel, Keith F.,Kohlbrenner, William E.,Molla, Akhteruzzaman,Adachi, Motoyasu,Tamada, Taro,Kuroki, Ryota,Katsuki, Noriko,Tanaka, Yoshiaki,Matsumoto, Hikaru,Wang, Jun,Hayashi, Yoshio,Kempf, Dale J.,Kiso, Yoshiaki
, p. 7604 - 7617 (2009)
A series of HIV protease inhibitor based on the allophenylnorstatine structure with various P2′ moieties were synthesized. Among these analogues, we discovered that a small allyl group would maintain potent enzyme inhibitory activity compared t
Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin
Hidaka, Koushi,Kimura, Tooru,Ruben, Adam J.,Uemura, Tsuyoshi,Kamiya, Mami,Kiso, Aiko,Okamoto, Tetsuya,Tsuchiya, Yumi,Hayashi, Yoshio,Freire, Ernesto,Kiso, Yoshiaki
scheme or table, p. 10049 - 10060 (2009/04/07)
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm.
