845834-64-2Relevant academic research and scientific papers
Forward- and reverse-synthesis of piperazinopiperidine amide analogs: A general access to structurally diverse 4-piperazinopiperidine-based CCR5 antagonists
Feng, Dong-Zhi,Song, Yan-Li,Jiang, Xiao-Hua,Chen, Li,Long, Ya-Qiu
, p. 2690 - 2697 (2008/03/12)
Piperazinopiperidine amide analogs are among the most promising CCR5 antagonists. As an effective extension of a previously-reported methodology to synthesize such compounds, forward- and reverse-syntheses were successfully developed in which the convergent synthesis of the piperazinopiperidine nucleus, with a building block of 4-substituent-4-aminopiperidine, served as a common key step. The two-way approach affords a comprehensive access to the piperazinopiperidine templated library with variation on the pharmacophore sites. Thus, a SAR study of our synthesized piperazinopiperidine-based CCR5 antagonists was conducted with respect to the structure and configuration of the substituent on the piperazine ring. The S-configuration of the benzylic-substituent is vital for the CCR5 binding, and the bulky or aryl substituent on the 2-position in the piperazine ring is detrimental to the activity. By using the forward-synthesis approach, the best compound in the chiral piperazine-based CCR5 antagonist series, Sch-D (Vicriviroc), was conveniently synthesized in an excellent yield. The Royal Society of Chemistry.
An improved synthesis of piperazino-piperidine based CCR5 antagonists with flexible variation on pharmacophore sites
Jiang, Xiao-Hua,Song, Yan-Li,Feng, Dong-Zhi,Long, Ya-Qiu
, p. 1281 - 1288 (2007/10/03)
An improved and efficient synthetic route towards piperidino-piperazine based CCR5 antagonists was developed. The new approach was flexible for introducing various substituents in the pharmacophore sites via Grignard reagent addition and reductive amination. l-Amino acids were used as a chiral pool to introduce and then induce the desired stereochemistries, meanwhile rendering the variable substitution. The efficient construction of the piperazino-piperidine nucleus was achieved in a highly convergent manner with a key building block of N1-Boc-4-substituent-4-aminopiperidine, exhibiting significant advantages in terms of concise synthetic route and environmental-friendly reagents over the previously described stepwise synthesis, in which a modified Strecker reaction was involved with highly toxic reagents such as diethylaluminum cyanide.
