Efficient synthesis and identification of novel propane-1,3-diamino bridged CCR5 antagonists with variation on the basic center carrier

Xing Fan; Hu-Shan Zhang; Li Chen; Ya-Qiu Long

doi:10.1016/j.ejmech.2010.03.003

Efficient synthesis and identification of novel propane-1,3-diamino bridged CCR5 antagonists with variation on the basic center carrier

Eur J Med Chem. 2010 Jul;45(7):2827-40. doi: 10.1016/j.ejmech.2010.03.003. Epub 2010 Mar 7.

Authors

Xing Fan¹, Hu-Shan Zhang, Li Chen, Ya-Qiu Long

Affiliation

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, CAS, 555 Zuchongzhi Road, Shanghai 201203, China.

PMID: 20347189
DOI: 10.1016/j.ejmech.2010.03.003

Abstract

By employing pharmacophore-based design and the privileged fragments reassembly, a series of piperidine-/tropane-/piperazine-bridged CCR5 antagonists were designed and synthesized via an efficient convergent synthesis strategy, with focus on the optimal choice of the basic center carrier structure. Significantly, the 4-amino-4-methylpiperidine bridged 1-acyl-1,3-propanediamine compounds were identified as a new class of nanomolar CCR5 antagonists, providing an efficient approach and novel scaffolds for further development of potent CCR5 inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemistry*
Animals
CCR5 Receptor Antagonists*
CHO Cells
Cricetinae
Cricetulus
Drug Design
Hydrophobic and Hydrophilic Interactions
Propane / chemical synthesis
Propane / chemistry*
Propane / pharmacology*

Substances

Amines
CCR5 Receptor Antagonists
Propane