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David J. St. Jean
Researcher at Amgen
Publications - 53
Citations - 1213
David J. St. Jean is an academic researcher from Amgen. The author has contributed to research in topics: Glucokinase regulatory protein & Glucokinase. The author has an hindex of 19, co-authored 51 publications receiving 1103 citations. Previous affiliations of David J. St. Jean include University of Pennsylvania.
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Journal ArticleDOI
Mitigating Heterocycle Metabolism in Drug Discovery
TL;DR: This review summarizes examples where changes were made at or near the heterocycle to improve metabolic stability of heterocycles and hopes to provide a useful guide to medicinal chemists as they attempt to improve the metabolic profile of their own heterocyclic compounds.
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From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1).
Yuan Cheng,Ted Judd,Michael D. Bartberger,James Brown,Kui Chen,Robert T. Fremeau,Dean Hickman,Stephen Hitchcock,Brad Jordan,Vivian S. W. Li,Patricia Lopez,Steven W. Louie,Yi Luo,Klaus Michelsen,Thomas Nixey,Timothy Powers,Claire Rattan,E. Allen Sickmier,David J. St. Jean,Robert C. Wahl,Paul H. Wen,Stephen J. Wood +21 more
TL;DR: It is shown that elaboration of the physical properties of the lead compounds to those more consistent with good blood-brain barrier permeability led to inhibitors with greatly improved cellular activity and permeability and improved the BACE1 potency to subnanomolar range.
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Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors.
David Lloyd,David J. St. Jean,Robert J.M. Kurzeja,Robert C. Wahl,Klaus Michelsen,Rod Cupples,Michelle Chen,John Wu,Glenn Sivits,Joan Helmering,Renee Komorowski,Kate Ashton,Lewis D. Pennington,Christopher H. Fotsch,Mukta Vazir,Kui Chen,Samer Chmait,Jiandong Zhang,Longbin Liu,Mark H. Norman,Kristin L. Andrews,Michael D. Bartberger,Gwyneth Van,Elizabeth J. Galbreath,Steven Vonderfecht,Minghan Wang,Steven R. Jordan,Murielle M. Véniant,Clarence Hale +28 more
TL;DR: Two potent small-molecule GK–GKRP disruptors (AMG-1694 and AMG-3969) are identified that normalized blood glucose levels in several rodent models of diabetes and exploit a new cellular mechanism for loweringBlood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.
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Discovery of a Potent, Orally Active 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor for Clinical Study: Identification of (S)-2-((1S,2S,4R)-Bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221)
Murielle M. Véniant,Clarence Hale,Randall W. Hungate,Kyung H. Gahm,Maurice Emery,Janan Jona,Smriti Joseph,Jeffrey Adams,Andrew Hague,George A. Moniz,Jiandong Zhang,Michael D. Bartberger,Vivian S. W. Li,Rashid Syed,Steven R. Jordan,Renee Komorowski,Michelle Chen,Rod Cupples,Ki Won Kim,David J. St. Jean,Lars Johansson,Martin Henriksson,Meredith Williams,Jerk Vallgarda,Christopher H. Fotsch,Minghan Wang +25 more
TL;DR: Thiazolones with an exo-norbornylamine at the 2-position and an isopropyl group on the 5-position are potent 11beta-HSD1 inhibitors, but the C-5 center was prone to epimerization in vitro and in vivo, forming a less potent diastereomer.
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A Tandem Cross-Coupling/SNAr Approach to Functionalized Carbazoles
TL;DR: A novel route to functionalized carbazoles utilizing a tandem Suzuki cross-coupling/SNAr protocol is described, found to be compatible with a variety of electron-withdrawing groups including aldehydes, esters, and sulfones.