title: Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors.
abstract: Compound 4 (PF-04971729) belongs to a new class of potent and selective sodium-dependent glucose cotransporter 2 inhibitors incorporating a unique dioxa-bicyclo[3.2.1]octane (bridged ketal) ring system. In this paper we present the design, synthesis, preclinical evaluation, and human dose predictions related to 4. This compound demonstrated robust urinary glucose excretion in rats and an excellent preclinical safety profile. It is currently in phase 2 clinical trials and is being evaluated for the treatment of type 2 diabetes.
authors: Groton Laboratories, Pfizer Global Research & Development, Groton, Connecticut 06340, United States. vincent.mascitti@pfizer.com
authors: Vincent
authors: V
authors: Mascitti
authors: Tristan S
authors: TS
authors: Maurer
authors: Ralph P
authors: RP
authors: Robinson
authors: Jianwei
authors: J
authors: Bian
authors: Carine M
authors: CM
authors: Boustany-Kari
authors: Thomas
authors: T
authors: Brandt
authors: Benjamin M
authors: BM
authors: Collman
authors: Amit S
authors: AS
authors: Kalgutkar
authors: Michelle K
authors: MK
authors: Klenotic
authors: Michael T
authors: MT
authors: Leininger
authors: André
authors: A
authors: Lowe
authors: Robert J
authors: RJ
authors: Maguire
authors: Victoria M
authors: VM
authors: Masterson
authors: Zhuang
authors: Z
authors: Miao
authors: Emi
authors: E
authors: Mukaiyama
authors: Jigna D
authors: JD
authors: Patel
authors: John C
authors: JC
authors: Pettersen
authors: Cathy
authors: C
authors: Préville
authors: Brian
authors: B
authors: Samas
authors: Li
authors: L
authors: She
authors: Zhanna
authors: Z
authors: Sobol
authors: Claire M
authors: CM
authors: Steppan
authors: Benjamin D
authors: BD
authors: Stevens
authors: Benjamin A
authors: BA
authors: Thuma
authors: Meera
authors: M
authors: Tugnait
authors: Dongxiang
authors: D
authors: Zeng
authors: Tong
authors: T
authors: Zhu
mesh_terms: D000818:Animals; D019540:Area Under Curve; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D051381:Rats; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D000077203:Sodium-Glucose Transporter 2 Inhibitors