title: Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists.
abstract: Preclinical studies suggest that compounds with dual norepinephrine reuptake inhibitor (NRI) and 5-HT(1A) partial agonist properties may provide an important new therapeutic approach to ADHD, depression, and anxiety. Reported herein is the discovery of a novel chemical series with a favorable NRI and 5-HT(1A) partial agonist pharmacological profile as well as excellent selectivity for the norepinephrine transporter over the dopamine transporter.
authors.affiliation: Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, United States. Amy.Dounay@pfizer.com
authors.forename: Amy B
authors.initials: AB
authors.lastname: Dounay
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Barta
authors.forename: Brian M
authors.initials: BM
authors.lastname: Campbell
authors.forename: Corey
authors.initials: C
authors.lastname: Coleman
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Collantes
authors.forename: Lynne
authors.initials: L
authors.lastname: Denny
authors.forename: Satavisha
authors.initials: S
authors.lastname: Dutta
authors.forename: David L
authors.initials: DL
authors.lastname: Gray
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Hou
authors.forename: Rathna
authors.initials: R
authors.lastname: Iyer
authors.forename: Samarendra N
authors.initials: SN
authors.lastname: Maiti
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Ortwine
authors.forename: Al
authors.initials: A
authors.lastname: Probert
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Stratman
authors.forename: Rajendra
authors.initials: R
authors.lastname: Subedi
authors.forename: Tammy
authors.initials: T
authors.lastname: Whisman
authors.forename: Wenjian
authors.initials: W
authors.lastname: Xu
authors.forename: Kim
authors.initials: K
authors.lastname: Zoski
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010636:Phenols / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010636:Phenols; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C042329:phenoxy radical