title: Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists.
abstract: Synthesis and structure-activity relationship (SAR) studies on 5-trifluoromethylpyrido[4,3-d]pyrimidin-4(3H)-ones, a novel class of calcium receptor antagonists is described with particular emphasis on optimization of the pharmacokinetic/pharmacodynamic parameters required for a short duration of action compound. Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects.
authors.affiliation: Pfizer Global Research and Development, Groton, CT 06340, United States. mary.didiuk@pfizer.com
authors.forename: Mary T
authors.initials: MT
authors.lastname: Didiuk
authors.forename: David A
authors.initials: DA
authors.lastname: Griffith
authors.forename: John W
authors.initials: JW
authors.lastname: Benbow
authors.forename: Kevin K C
authors.initials: KK
authors.lastname: Liu
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Walker
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Bi
authors.forename: Joel
authors.initials: J
authors.lastname: Morris
authors.forename: Angel
authors.initials: A
authors.lastname: Guzman-Perez
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Bechle
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Kelley
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dirico
authors.forename: Syed
authors.initials: S
authors.lastname: Ahmed
authors.forename: William
authors.initials: W
authors.lastname: Hungerford
authors.forename: Joseph
authors.initials: J
authors.lastname: DiBrinno
authors.forename: Michael P
authors.initials: MP
authors.lastname: Zawistoski
authors.forename: Scott W
authors.initials: SW
authors.lastname: Bagley
authors.forename: Jianke
authors.initials: J
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Stephanie
authors.initials: S
authors.lastname: Santucci
authors.forename: Robert
authors.initials: R
authors.lastname: Oliver
authors.forename: Matthew
authors.initials: M
authors.lastname: Corbett
authors.forename: Thanh
authors.initials: T
authors.lastname: Olson
authors.forename: Chiliu
authors.initials: C
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Vishwas M
authors.initials: VM
authors.lastname: Paralkar
authors.forename: Keith A
authors.initials: KA
authors.lastname: Riccardi
authors.forename: David R
authors.initials: DR
authors.lastname: Healy
authors.forename: Amit S
authors.initials: AS
authors.lastname: Kalgutkar
authors.forename: Tristan S
authors.initials: TS
authors.lastname: Maurer
authors.forename: Hang T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Kosea S
authors.initials: KS
authors.lastname: Frederick
mesh_terms: D000284:Administration, Oral; D045930:Anabolic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism; D011744:Pyrimidinones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D045930:Anabolic Agents; D010281:Parathyroid Hormone; D011744:Pyrimidinones; D044169:Receptors, Calcium-Sensing