Design of substituted imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 antagonists: potent inhibitors of R5 HIV-1 replication

R Skerlj, G Bridger, Y Zhou, E Bourque…

文献索引：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 Journal of Medicinal Chemistry, 2013 , vol. 56, # 20 p. 8049 - 8065

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被引用次数: 5

摘要

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 ( ...