title: Use of receptor chimeras to identify small molecules with high affinity for the dynorphin A binding domain of the kappa opioid receptor.
abstract: A series of 2-substituted sulfamoyl arylacetamides of general structure 2 were prepared as potent kappa opioid receptor agonists and the affinities of these compounds for opioid and chimeric receptors were compared with those of dynorphin A. Compounds 2e and 2i were identified as non-peptide small molecules that bound to chimeras 3 and 4 with high affinities similar to dynorphin A, resulting in K(i) values of 1.5 and 1.2 nM and 1.3 and 2.2 nM, respectively.
authors.affiliation: Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. vkumar@adolor.com
authors.forename: Virendra
authors.initials: V
authors.lastname: Kumar
authors.forename: Deqi
authors.initials: D
authors.lastname: Guo
authors.forename: Michael
authors.initials: M
authors.lastname: Marella
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cassel
authors.forename: Robert N
authors.initials: RN
authors.lastname: Dehaven
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Daubert
authors.forename: Erik
authors.initials: E
authors.lastname: Mansson
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004399:Dynorphins / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D008970:Molecular Weight; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D017473:Receptors, Opioid, kappa; D011993:Recombinant Fusion Proteins; D054852:Small Molecule Libraries; D004399:Dynorphins