Antagonists of human CCR5 receptor containing 4-(pyrazolyl) piperidine side chains. Part 3: SAR studies on the benzylpyrazole segment

…, DM Shen, L Malkowitz, MS Springer, SL Gould…

Index: Shu, Min; Loebach, Jennifer L.; Parker, Kerry A.; Mills, Sander G.; Chapman, Kevin T.; Shen, Dong-Ming; Malkowitz, Lorraine; Springer, Martin S.; Gould, Sandra L.; DeMartino, Julie A.; Siciliano, Salvatore J.; Di Salvo, Jerry; Lyons, Kathy; Pivnichny, James V.; Kwei, Gloria Y.; Carella, Anthony; Carver, Gwen; Holmes, Karen; Schleif, William A.; Danzeisen, Renee; Hazuda, Daria; Kessler, Joseph; Lineberger, Janet; Miller, Michael D.; Emini, Emilio A. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 4 p. 947 - 952

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Citation Number: 42

Abstract

Extensive SAR studies in our benzylpyrazole series of CCR5 antagonists have shown that both lipophilic and hydrophilic substituents on the phenyl of the benzyl group increase antiviral potency. However, improvements in pharmacokinetic profiles were generally only observed with more lipophilic substitutions. 4-Biphenyl (51) performed the best in this regard. Highly lipophilic substituents impart undesirable ion channel activity to these ...