title: Investigation of piperazine benzamides as human β3adrenergic receptor agonists for the treatment of overactive bladder.
abstract: The synthesis of a novel class of piperazine benzamide (reverse amides) targeting the human β3-adrenergic receptor for the treatment of overactive bladder (OAB) is described. The SAR studies directed towards maintaining well established β3potency and selectivities while improving the overall pharmacokinetic profile in the reverse amide class will be evaluated. The results and consequences associated with functional activity at the norepinephrine transporter (NET) will also be discussed.
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States. Electronic address: bart_harper@merck.com.
authors.forename: Bart H
authors.initials: BH
authors.lastname: Harper
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Nam F
authors.initials: NF
authors.lastname: Kar
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Moyes
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Goble
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Costa
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Karen
authors.initials: K
authors.lastname: Dingley
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Jerry
authors.initials: J
authors.lastname: Di Salvo
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Sookhee N
authors.initials: SN
authors.lastname: Ha
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hurley
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Li
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Randy R
authors.initials: RR
authors.lastname: Miller
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagabukuro
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Gino M
authors.initials: GM
authors.lastname: Salituro
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Sean
authors.initials: S
authors.lastname: Smith
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Struthers
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
authors.affiliation: Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ 07065, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Berger
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D010879:Piperazines
keywords: Norepinephrine transporter; Overactive bladder; Pyrrolidine scaffold; Reverse amide; β(3)-Adrenergic receptor agonist