title: An aryloxypropanolamine hβ3-adrenoceptor agonist as bladder smooth muscle relaxant.
abstract: The relaxant effect of an aryloxypropanolamine β3-adrenoceptor agonist on carbachol pre-contracted human detrusor muscle strips was evaluated and compared with literature results from reference compounds of similar mode of action, including mirabegron. A significant relaxation was observed for rac-4-{2-hydroxy-3-[1-(5-phenylthieno[2,3-d]pyrimidin-4-yl)piperidin-4-ylamino]propoxy}-2-(hydroxymethyl)phenol which was similar to that exerted by mirabegron. In order to allow for a thorough discussion of results in comparison to reference compounds, their affinity, selectivity and efficacy as hβ3-AR agonists have been evaluated and discussed thoroughly. A ranking of hβ3-AR agonists by relative efficacy resulted in the closest analogy to the order of relaxation potential, with only the relaxant effect of mirabegron not reflecting its excellent relative efficacy as such.
authors.affiliation: 4SC Discovery GmbH, Am Klopferspitz 19a, 82152 Planegg-Martinsried, Germany. stefan.tasler@4sc.com
authors.forename: Stefan
authors.initials: S
authors.lastname: Tasler
authors.forename: Roland
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Delphine
authors.initials: D
authors.lastname: Behr-Roussel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Oger-Roussel
authors.forename: Diane
authors.initials: D
authors.lastname: Gorny
authors.forename: Francois
authors.initials: F
authors.lastname: Giuliano
authors.forename: Peter
authors.initials: P
authors.lastname: Ney
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000368:Aged; D000814:Aniline Compounds / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001713:Biphenyl Compounds; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D000814:Aniline Compounds; D001565:Benzoates; D001713:Biphenyl Compounds; D008024:Ligands; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D013844:Thiazoles; C523977:solabegron; D002217:Carbachol; C520025:mirabegron