301222-08-2Relevant academic research and scientific papers
Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 3: SAR studies on the benzylpyrazole segment
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.
, p. 947 - 952 (2007/10/03)
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 CCR5 antagonists. Alkoxy substituents provide a good balance of antiviral activity, pharmacokinetic parameters, and selectivity. Compounds 42b and 42d, containing a 3,4-dimethoxy substituent, are considered the most promising improvements over parent compounds 9. They demonstrate improved antiviral activity while retaining good pharmacokinetic profile and selectivity.
Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 2: Discovery of potent, selective, and orally bioavailable compounds
Shen, Dong-Ming,Shu, Min,Willoughby, Christopher A.,Shah, Shrenik,Lynch, Christopher L.,Hale, Jeffrey J.,Mills, Sander G.,Chapman, Kevin T.,Malkowitz, Lorraine,Springer, Martin S.,Gould, Sandra L.,DeMartino, Julie A.,Siciliano, Salvatore J.,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.
, p. 941 - 945 (2007/10/03)
Modifications of the alkyl acetic acid portion and the phenyl on pyrrolidine in our lead pyrazole compound 1 afforded the isopropyl compound 9. This compound is a potent CCR5 antagonist showing good in vitro antiviral activity against HIV-1, an excellent
