title: Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective beta(2)-adrenergic receptor agonists.
abstract: OBJECTIVE
  To use a previously developed CoMFA model to design a series of new structures of high selectivity and efficacy towards the beta(2)-adrenergic receptor.
  
  
  RESULTS
  Out of 21 computationally designed structures 6 compounds were synthesized and characterized for beta(2)-AR binding affinities, subtype selectivities and functional activities.
  
  
  CONCLUSIONS
  the best compound is (R,R)-4-methoxy-1-naphthylfelnoterol with K(i)beta(2)-AR=0.28microm, K(i)beta(1)-AR/K(i)beta(2)-AR=573, EC(50cAMP)=3.9nm, EC(50cardio)=16nm. The CoMFA model appears to be an effective predictor of the cardiomocyte contractility of the studied compounds which are targeted for use in congestive heart failure.
authors.affiliation: Department of Chemistry, Medical University of Lublin, Lublin, Poland. krzysztof.jozwiak@umlub.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jozwiak
authors.forename: Anthony Yiu-Ho
authors.initials: AY
authors.lastname: Woo
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Tanga
authors.forename: Lawrence
authors.initials: L
authors.lastname: Toll
authors.forename: Lucita
authors.initials: L
authors.lastname: Jimenez
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozocas
authors.forename: Anita
authors.initials: A
authors.lastname: Plazinska
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Xiao
authors.forename: Irving W
authors.initials: IW
authors.lastname: Wainer
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D001665:Binding Sites; D002460:Cell Line; D005280:Fenoterol / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D018343:Receptors, Adrenergic, beta-2 / Q000276:immunology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D005280:Fenoterol