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.
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.
Chen
Chixu
C
Department of Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. cchen9@san.rr.com
Stearns
Brian
B
Hu
Tao
T
Anker
Naomi
N
Santini
Angelina
A
Arruda
Jeannie M
JM
Campbell
Brian T
BT
Datta
Purabi
P
Aiyar
Jayashree
J
Munoz
Benitio
B
D015220:Calcium Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D006801:Humans; D015640:Ion Channel Gating; D008024:Ligands; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism*; D012996:Solutions / Q000737:chemistry; D013329:Structure-Activity Relationship
D015220:Calcium Channels; D008024:Ligands; D021122:Protein Subunits; D012996:Solutions; C494035:voltage gated calcium channel subunit Ca alpha2delta-1, human