title: Discovery of Spirocyclic Aldosterone Synthase Inhibitors as Potential Treatments for Resistant Hypertension.
abstract: Herein we report the discovery and hit-to-lead optimization of a series of spirocyclic piperidine aldosterone synthase (CYP11B2) inhibitors. Compounds from this series display potent CYP11B2 inhibition, good selectivity versus related CYP enzymes, and lead-like physical and pharmacokinetic properties.
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Whitney L
authors.initials: WL
authors.lastname: Petrilli
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Hoyt
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Clare
authors.initials: C
authors.lastname: London
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: McMasters
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Verras
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Struthers
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Doris
authors.initials: D
authors.lastname: Cully
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Charlene
authors.initials: C
authors.lastname: Bopp
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sok
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Elaine
authors.initials: E
authors.lastname: Tung
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Gino
authors.initials: G
authors.lastname: Salituro
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Ian
authors.initials: I
authors.lastname: Knemeyer
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Bindhu
authors.initials: B
authors.lastname: Karanam
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Clemas
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Gaochao
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Jack
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Carrie Ann
authors.initials: CA
authors.lastname: Shipley
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: MacNeil
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Ruth
authors.initials: R
authors.lastname: Duffy
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Tata
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Feroze
authors.initials: F
authors.lastname: Ujjainwalla
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Amjad
authors.initials: A
authors.lastname: Ali
authors.affiliation: Departments of Discovery Chemistry, Chemistry Modeling & Informatics, Hypertension, Drug Metabolism & Pharmacokinetics, and In Vitro Pharmacology, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Xiong
keywords: CYP11B2; aldosterone synthase; hypertension