78725-48-1Relevant articles and documents
Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity
Jia, Ruifang,Zhang, Jian,Bertagnin, Chiara,Cherukupalli, Srinivasulu,Ai, Wei,Ding, Xiao,Li, Zhuo,Zhang, Jiwei,Ju, Han,Ma, Xiuli,Loregian, Arianna,Huang, Bing,Zhan, Peng,Liu, Xinyong
, (2021/01/05)
Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C5–NH2 of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1–H274Y). Specifically, there was 30-fold loss of activity against the wild-type strain H1N1. However, 5c displayed 4.85-fold more potent activity than OSC against H5N1–H274Y NA. Also, 5c demonstrated low cytotoxicity in vitro and no acute toxicity in mice. Molecular docking studies provided insights into the high potency of 5c against N1 and N1–H274Y mutant NAs. Besides, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability of representative compounds were conducted to evaluate their drug-like properties.
A Corey–Seebach Macrocyclisation Strategy for the Synthesis of Riccardin C and an Unnatural Macrocyclic Bis(bibenzyl) Analogue
Almalki, Faisal A.,Harrowven, David C.
, p. 5738 - 5746 (2016/12/14)
A total synthesis of riccardin C has been accomplished using a Corey–Seebach reaction to effect macrocyclisation. The versatility of the strategy has also been demonstrated with a mimetic synthesis of an unnatural bis(bibenzyl) analogue.
Discovery of N-{4-[(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2- methylpropyl}-4-phenoxybenzamide analogues as selective kappa opioid receptor antagonists
Kormos, Chad M.,Jin, Chunyang,Cueva, Juan Pablo,Runyon, Scott P.,Thomas, James B.,Brieaddy, Lawrence E.,Mascarella, S. Wayne,Navarro, Hernán A.,Gilmour, Brian P.,Carroll, F. Ivy
, p. 4551 - 4567 (2013/07/19)
There is continuing interest in the discovery and development of new κ opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [35S] GTPγS binding assay showed that neither compound showed the high potency and κ opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [35S]GTPγS binding stimulated by the selective κ opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3- methylpiperazin-1-yl]methyl}-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good κ opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [35S]GTPγS binding assay showed that several of the analogues were potent and selective κ opioid receptor antagonists.
