@article{e49cb34bd7734427bc9420a2af98c33d,
title = "SAR studies of 4-acyl-1,6-dialkylpiperazin-2-one arenavirus cell entry inhibitors",
abstract = "Old World (Africa) and New World (South America) arenaviruses are associated with human hemorrhagic fevers. Efforts to develop small molecule therapeutics have yielded several chemical series including the 4-acyl-1,6-dialkylpiperazin-2-ones. Herein, we describe an extensive exploration of this chemotype. In initial Phase I studies, R1 and R4 scanning libraries were assayed to identify potent substituents against Old World (Lassa) virus. In subsequent Phase II studies, R6 substituents and iterative R1, R4 and R6 substituent combinations were evaluated to obtain compounds with improved Lassa and New World (Machupo, Junin, and Tacaribe) arenavirus inhibitory activity, in vitro human liver microsome metabolic stability and aqueous solubility.",
keywords = "Arenavirus, Entry inhibitor, Junin, Lassa, Machupo, Piperazinone",
author = "Plewe, {Michael B.} and Whitby, {Landon R.} and Shibani Naik and Brown, {Eric R.} and Sokolova, {Nadezda V.} and Gantla, {Vidyasagar Reddy} and Joanne York and Nunberg, {Jack H.} and Lihong Zhang and Birte Kalveram and Freiberg, {Alexander N.} and Boger, {Dale L.} and Greg Henkel and Ken McCormack",
note = "Funding Information: We gratefully acknowledge the financial support of the National Institutes of Health ( R43AI112097 to K.M and M.B.P.; R44AI112097 to G.H.; CA042056 to D.L.B.; AI074818 and AI065357 to J.H.N) and the generous gifts of arenavirus glycoprotein plasmid constructs and pseudotyped vectors from Juan Carlos de la Torre and Brian Hjelle. The replicative Tacaribe virus TRVL-11573 and monoclonal anti-JUNV, clone MA03-BE06 were obtained from BEI Resources, NIAID, NIH. Funding Information: We gratefully acknowledge the financial support of the National Institutes of Health (R43AI112097 to K.M and M.B.P.; R44AI112097 to G.H.; CA042056 to D.L.B.; AI074818 and AI065357 to J.H.N) and the generous gifts of arenavirus glycoprotein plasmid constructs and pseudotyped vectors from Juan Carlos de la Torre and Brian Hjelle. The replicative Tacaribe virus TRVL-11573 and monoclonal anti-JUNV, clone MA03-BE06 were obtained from BEI Resources, NIAID, NIH. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = nov,
day = "15",
doi = "10.1016/j.bmcl.2019.08.024",
language = "English (US)",
volume = "29",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "22",
}