title: Inhibition of N-type calcium channels by fluorophenoxyanilide derivatives.
abstract: A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed.
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. ellen.gleeson@monash.edu.|CSIRO Manufacturing Flagship, Clayton South, VIC 3169, Australia. ellen.gleeson@monash.edu.
authors: Ellen C
authors: EC
authors: Gleeson
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. janease.graham@gmail.com.|CSIRO Manufacturing Flagship, Clayton South, VIC 3169, Australia. janease.graham@gmail.com.
authors: Janease E
authors: JE
authors: Graham
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. sandro.spiller@bbz.uni-leipzig.de.
authors: Sandro
authors: S
authors: Spiller
authors: Institute for Molecular Bioscience, The University of Queensland, St Lucia QLD 4072, Australia. i.vetter@imb.uq.edu.au.
authors: Irina
authors: I
authors: Vetter
authors: Institute for Molecular Bioscience, The University of Queensland, St Lucia QLD 4072, Australia. r.lewis@imb.uq.edu.au.
authors: Richard J
authors: RJ
authors: Lewis
authors: CSIRO Manufacturing Flagship, Clayton South, VIC 3169, Australia. peter.duggan@csiro.au.|School of Chemical and Physical Sciences, Flinders University, Adelaide SA 5042, Australia. peter.duggan@csiro.au.
authors: Peter J
authors: PJ
authors: Duggan
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. kellie.tuck@monash.edu.
authors: Kellie L
authors: KL
authors: Tuck
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D015195:Drug Design; D005464:Fluorobenzenes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry; D010148:Intractable Pain / Q000188:drug therapy / Q000378:metabolism; D013329:Structure-Activity Relationship; D020866:omega-Conotoxin GVIA / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018712:Analgesics, Non-Narcotic; D000813:Anilides; C500545:CACNA1B protein, human; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D005464:Fluorobenzenes; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D020866:omega-Conotoxin GVIA