160748-01-6Relevant academic research and scientific papers
Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere
Mimoto, Tsutomu,Hattori, Naoko,Takaku, Haruo,Kisanuki, Sumitsugu,Fukazawa, Tominaga,Terashima, Keisuke,Kato, Ryohei,Nojima, Satoshi,Misawa, Satoru,Ueno, Takamasa,Imai, Junya,Enomoto, Hiroshi,Tanaka, Shigeki,Sakikawa, Hiroshi,Shintani, Makoto,Hayashi, Hideya,Kiso, Yoshiaki
, p. 1310 - 1326 (2007/10/03)
We designed and synthesized a new class of peptidomimetic human immunodeficiency virus protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], with a hydroxymethylcarbonyl isostere as the active moiety. From a structure-activity relationship study of HIV-1 protease inhibition, enzyme selectivity for other aspartyl proteases, the antiviral activity and pharmacokinetics in rats, 24c (KNI-227) and 24d (KNI-272, our first clinical candidate) were found to be selective and orally potent HIV protease inhibitors. Moreover, an improvement of the pharmacokinetic features of KNI-272 provided two long-lasting and highly bioavailable compounds (24g: JE-2178,h: JE-2179).
Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: Conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine
Mimoto,Imai,Kisanuki,Enomoto,Hattori,Akaji,Kiso
, p. 2251 - 2253 (2007/10/02)
Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition-state mimic were designed and synthesized. Among them, conformationally constrained tripeptide derivatives,
