title: N-Acridin-9-yl-butane-1,4-diamine derivatives: high-affinity ligands of the alpha2delta subunit of voltage gated calcium channels.
abstract: 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.
authors.affiliation: Department of Chemistry, Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA. jongwon_lim@merck.com
authors.forename: Jongwon
authors.initials: J
authors.lastname: Lim
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stock
authors.forename: Richard
authors.initials: R
authors.lastname: Pracitto
authors.forename: Julia K
authors.initials: JK
authors.lastname: Boueres
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
authors.forename: Ashok
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Angelina M
authors.initials: AM
authors.lastname: Santini
authors.forename: Karia
authors.initials: K
authors.lastname: Orr
authors.forename: Hervé
authors.initials: H
authors.lastname: Schaffhauser
authors.forename: Robert E
authors.initials: RE
authors.lastname: Bezverkov
authors.forename: Jayashree
authors.initials: J
authors.lastname: Aiyar
authors.forename: Shankar
authors.initials: S
authors.lastname: Venkatraman
mesh_terms: 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
chemical_list: D000085:Acetates; D000588:Amines; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D003959:Diamines; D008024:Ligands; D021122:Protein Subunits; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin