N-Acridin-9-yl-butane-1,4-diamine derivatives: high-affinity ligands of the alpha2delta subunit of voltage gated calcium channels.
A series of N-acridin-9-yl-butane-1,4-diamines were found to be high-affinity ligands of the alpha(2)delta subunit of voltage gated calcium channels. The SAR studies of butane-1,4-diamine side chain resulted in the identification of compound 10 (IC(50)=9 nM), which is more potent than gabapentin (IC(50)=27 nM). Partial saturation of the acridine ring was also pursued and provided a compound with higher binding affinity than 1.
Lim
Jongwon
J
Department of Chemistry, Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA. jongwon_lim@merck.com
Stock
Nicholas
N
Pracitto
Richard
R
Boueres
Julia K
JK
Munoz
Benito
B
Chaudhary
Ashok
A
Santini
Angelina M
AM
Orr
Karia
K
Schaffhauser
Hervé
H
Bezverkov
Robert E
RE
Aiyar
Jayashree
J
Venkatraman
Shankar
S
D000085:Acetates / Q000494:pharmacology; D000588:Amines; D001667:Binding, Competitive / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003509:Cyclohexanecarboxylic Acids; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000077206:Gabapentin; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D003959:Diamines; D008024:Ligands; D021122:Protein Subunits; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin