Literature DB >> 24462664

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: development of a [3.3.0]-based series and other piperidine bioisosteres.

Douglas J Sheffler1, Michael T Nedelcovych2, Richard Williams3, Stephen C Turner4, Brittany B Duerk4, Megan R Robbins4, Sataya B Jadhav5, Colleen M Niswender6, Carrie K Jones2, P Jeffrey Conn6, R Nathan Daniels7, Craig W Lindsley8.   

Abstract

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores.
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  GlyT1; Scaffold hopping; Schizophrenia; Transporter

Mesh：

Substances：

Year:  2014        PMID： 24462664      PMCID： PMC3951244          DOI： 10.1016/j.bmcl.2014.01.011

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  18 in total

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Authors:  John A Lowe; Xinjun Hou; Christopher Schmidt; F David Tingley; Stan McHardy; Monica Kalman; Shari Deninno; Mark Sanner; Karen Ward; Lorraine Lebel; Don Tunucci; James Valentine; Brian S Bronk; Eric Schaeffer
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2.  The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease.

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Journal:  ACS Chem Neurosci       Date:  2011-12-21       Impact factor: 4.418

3.  Synthesis and SAR of 4-aminocyclopentapyrrolidines as N-type Ca²⁺ channel blockers with analgesic activity.

Authors:  Xenia Beebe; Daria Darczak; Rodger F Henry; Timothy Vortherms; Richard Janis; Marian Namovic; Diana Donnelly-Roberts; Karen L Kage; Carol Surowy; Ivan Milicic; Wende Niforatos; Andrew Swensen; Kennan C Marsh; Jill M Wetter; Pamela Franklin; Scott Baker; Chengmin Zhong; Gricelda Simler; Erica Gomez; Janel M Boyce-Rustay; Chang Z Zhu; Andrew O Stewart; Michael F Jarvis; Victoria E Scott
Journal:  Bioorg Med Chem       Date:  2012-05-04       Impact factor: 3.641

Review 4.  Classification of scaffold-hopping approaches.

Authors:  Hongmao Sun; Gregory Tawa; Anders Wallqvist
Journal:  Drug Discov Today       Date:  2011-10-26       Impact factor: 7.851

Review 5.  Glycine transporter-1: a new potential therapeutic target for schizophrenia.

Authors:  Kenji Hashimoto
Journal:  Curr Pharm Des       Date:  2011       Impact factor: 3.116

6.  Chiral proton catalysis of secondary nitroalkane additions to azomethine: synthesis of a potent GlyT1 inhibitor.

Authors:  Tyler A Davis; Michael W Danneman; Jeffrey N Johnston
Journal:  Chem Commun (Camb)       Date:  2012-04-30       Impact factor: 6.222

Review 7.  Recent progress in the discovery of non-sarcosine based GlyT1 inhibitors.

Authors:  Scott E Wolkenberg; Cyrille Sur
Journal:  Curr Top Med Chem       Date:  2010       Impact factor: 3.295

8.  Discovery of GlyT1 inhibitors with improved pharmacokinetic properties.

Authors:  Scott E Wolkenberg; Zhijian Zhao; David D Wisnoski; William H Leister; Julie O'Brien; Wei Lemaire; David L Williams; Marlene A Jacobson; Cyrille Sur; Gene G Kinney; Doug J Pettibone; Philip R Tiller; Sheri Smith; Christopher Gibson; Bennett K Ma; Stacey L Polsky-Fisher; Craig W Lindsley; George D Hartman
Journal:  Bioorg Med Chem Lett       Date:  2009-01-10       Impact factor: 2.823

Review 9.  Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks.

Authors:  Frank S Menniti; Craig W Lindsley; P Jeffrey Conn; Jayvardhan Pandit; Panayiotis Zagouras; Robert A Volkmann
Journal:  Curr Top Med Chem       Date:  2013       Impact factor: 3.295

10.  Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1.

Authors:  Jason T Manka; Alice L Rodriguez; Ryan D Morrison; Daryl F Venable; Hyekyung P Cho; Anna L Blobaum; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2013-07-23       Impact factor: 2.823
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  2 in total

1.  Discovery of a novel 2,4-dimethylquinoline-6-carboxamide M4 positive allosteric modulator (PAM) chemotype via scaffold hopping.

Authors:  Madeline F Long; Julie L Engers; Sichen Chang; Xiaoyan Zhan; Rebecca L Weiner; Vincent B Luscombe; Alice L Rodriguez; Hyekyung P Cho; Colleen M Niswender; Thomas M Bridges; P Jeffrey Conn; Darren W Engers; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2017-10-09       Impact factor: 2.823

2.  Analysis of Binding Determinants for Different Classes of Competitive and Noncompetitive Inhibitors of Glycine Transporters.

Authors:  Kamil Łątka; Marek Bajda
Journal:  Int J Mol Sci       Date:  2022-07-21       Impact factor: 6.208
  2 in total

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