851547-97-2Relevant academic research and scientific papers
Identification of Potent Ebola Virus Entry Inhibitors with Suitable Properties for in Vivo Studies
Liu, Hu,Tian, Ye,Lee, Kyungae,Krishnan, Pranav,Wang, May Kwang-Mei,Whelan, Sean,Mevers, Emily,Soloveva, Veronica,Dedic, Benjamin,Liu, Xinyong,Cunningham, James M.
supporting information, p. 6293 - 6307 (2018/06/27)
Previous studies identified an adamantane dipeptide piperazine 3.47 that inhibits Ebola virus (EBOV) infection by targeting the essential receptor Niemann-Pick C1 (NPC1). The physicochemical properties of 3.47 limit its potential for testing in vivo. Optimization by improving potency, reducing hydrophobicity, and replacing labile moieties identified 3.47 derivatives with improved in vitro ADME properties that are also highly active against EBOV infection, including when tested in the presence of 50% normal human serum (NHS). In addition, 3A4 was identified as the major cytochrome P450 isoform that metabolizes these compounds, and accordingly, mouse microsome stability was significantly improved when tested in the presence of the CYP3A4 inhibitor ritonavir that is approved for clinical use as a booster of anti-HIV drugs. Oral administration of the EBOV inhibitors with ritonavir resulted in a pharmacokinetic profile that supports a b.i.d. dosing regimen for efficacy studies in mice.
CCR5 receptor antagonists: Discovery and SAR study of guanylhydrazone derivatives
Wei, Robert G.,Arnaiz, Damian O.,Chou, Yuo-Ling,Davey, Dave,Dunning, Laura,Lee, Wheeseong,Lu, Shou-Fu,Onuffer, James,Ye, Bin,Phillips, Gary
, p. 231 - 234 (2007/10/03)
High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.
BENZYLETHER AMINE COMPOUNDS USEFUL AS CCR-5 ANTAGONISTS
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Page/Page column 37, (2010/02/11)
The present invention relates to compounds which are CCR-5 receptor antagonists of the general formula I: wherein R1, R2, R3, R4, Ra, Rb, Rc, Rd, X, m and n are as defined herein. The invention further comprises pharmaeceutical compositions comprising suc
