Design, synthesis and structure-activity relationships of zwitterionic spirocyclic compounds as potent CCR1 antagonists

Nafizal Hossain; Svetlana Ivanova; Åsa Sjöholm Timén; Jonas Bergare; Tesfaledet Mussie; Lena Bergström

doi:10.1016/j.bmcl.2013.05.087

Design, synthesis and structure-activity relationships of zwitterionic spirocyclic compounds as potent CCR1 antagonists

Bioorg Med Chem Lett. 2013 Jul 15;23(14):4026-30. doi: 10.1016/j.bmcl.2013.05.087. Epub 2013 Jun 6.

Authors

Nafizal Hossain¹, Svetlana Ivanova, Åsa Sjöholm Timén, Jonas Bergare, Tesfaledet Mussie, Lena Bergström

Affiliation

¹ Department of Medicinal Chemistry, Respiratory Inflammation and Autoimmunity Innovative Medicines, AstraZeneca R&D, Pepparedsleden 1, SE-431 83 Mölndal, Sweden. nafizal.hossain@astrazeneca.com

PMID: 23769642
DOI: 10.1016/j.bmcl.2013.05.087

Abstract

A series of zwitterionic spirocyclic compounds were synthesised. In vitro data revealed that these compounds were potent CCR1 antagonists. In particular, 2, 4, 11 and 20 inhibited CCR1 mediated chemotaxis of THP-1 cells in a functional assay.

MeSH terms

Cell Line, Tumor
Chemotaxis / drug effects
Drug Design*
Humans
Protein Binding
Receptors, CCR1 / antagonists & inhibitors*
Receptors, CCR1 / metabolism
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry*
Spiro Compounds / pharmacology
Structure-Activity Relationship

Substances

Receptors, CCR1
Spiro Compounds