Expedited SAR study of high-affinity ligands to the alpha(2)delta subunit of voltage-gated calcium channels: Generation of a focused library using a solution-phase Sn2Ar coupling methodology

Chixu Chen; Brian Stearns; Tao Hu; Naomi Anker; Angelina Santini; Jeannie M Arruda; Brian T Campbell; Purabi Datta; Jayashree Aiyar; Benitio Munoz

doi:10.1016/j.bmcl.2005.08.117

Expedited SAR study of high-affinity ligands to the alpha(2)delta subunit of voltage-gated calcium channels: Generation of a focused library using a solution-phase Sn2Ar coupling methodology

Bioorg Med Chem Lett. 2006 Feb;16(3):746-9. doi: 10.1016/j.bmcl.2005.08.117.

Authors

Chixu Chen¹, Brian Stearns, Tao Hu, Naomi Anker, Angelina Santini, Jeannie M Arruda, Brian T Campbell, Purabi Datta, Jayashree Aiyar, Benitio Munoz

Affiliation

¹ Department of Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. [email protected]

PMID: 16321528
DOI: 10.1016/j.bmcl.2005.08.117

Abstract

The SAR of the lead compound 3, a novel ligand for the alpha(2)delta subunit of voltage-gated calcium channels, was rapidly explored. Utilizing a parallel solution-phase Sn2Ar coupling approach, a focused library was obtained. The library was evaluated in vitro and afforded a series of analogues with improved potencies. The SAR trends of the library are also described.

MeSH terms

Calcium Channels / chemistry
Calcium Channels / drug effects
Calcium Channels / metabolism*
Combinatorial Chemistry Techniques / methods*
Humans
Ion Channel Gating*
Ligands
Protein Subunits / chemistry
Protein Subunits / metabolism*
Solutions / chemistry
Structure-Activity Relationship

Substances

Calcium Channels
Ligands
Protein Subunits
Solutions
voltage gated calcium channel subunit Ca alpha2delta-1, human