926293-43-8Relevant articles and documents
Design of substituted imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 antagonists: Potent inhibitors of R5 HIV-1 replication
Skerlj, Renato,Bridger, Gary,Zhou, Yuanxi,Bourque, Elyse,McEachern, Ernest,Metz, Markus,Harwig, Curtis,Li, Tong-Shuang,Yang, Wen,Bogucki, David,Zhu, Yongbao,Langille, Jonathan,Veale, Duane,Ba, Tuya,Bey, Michael,Baird, Ian,Kaller, Alan,Krumpak, Maria,Leitch, David,Satori, Michael,Vocadlo, Krystyna,Guay, Danielle,Nan, Susan,Yee, Helen,Crawford, Jason,Chen, Gang,Wilson, Trevor,Carpenter, Bryon,Gauthier, David,MacFarland, Ron,Mosi, Renee,Bodart, Veronique,Wong, Rebecca,Fricker, Simon,Schols, Dominique
, p. 8049 - 8065 (2013/11/06)
The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure-activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further evaluated for receptor selectivity, antiviral activity against CCR5 using (R5) HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these results, 6d and 6h were selected for further development.
CHEMOKINE RECEPTOR BINDING COMPOUNDS
-
Page/Page column 26; 46, (2010/11/26)
The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR4 or CCR5. In one aspect, these compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).