Literature DB >> 24461352

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 1: development of a potent and CNS penetrant [3.1.0]-based lead.

Carrie K Jones1, Douglas J Sheffler1, Richard Williams2, Sataya B Jadhav2, Andrew S Felts3, Ryan D Morrison3, Colleen M Niswender3, J Scott Daniels3, P Jeffrey Conn3, Craig W Lindsley4.   

Abstract

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach that provided a robust intellectual property position, in lieu of a traditional, expensive HTS campaign. Members within this new [3.1.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, CNS penetration and efficacy in a preclinical model of schizophrenia (prepulse inhibition).
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  GlyT1; Scaffold hopping; Schizophrenia; Transporter

Mesh：

Substances：

Year:  2014        PMID： 24461352      PMCID： PMC3951249          DOI： 10.1016/j.bmcl.2014.01.013

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


  19 in total

1.  The discovery of a structurally novel class of inhibitors of the type 1 glycine transporter.

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
Journal:  Bioorg Med Chem Lett       Date:  2009-04-18       Impact factor: 2.823

2.  Mild and practical method for the alpha-arylation of nitriles with heteroaryl halides.

Authors:  Artis Klapars; Jacob H Waldman; Kevin R Campos; Mark S Jensen; Mark McLaughlin; John Y L Chung; Raymond J Cvetovich; Cheng-Yi Chen
Journal:  J Org Chem       Date:  2005-11-25       Impact factor: 4.354

3.  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.

Authors:  Zixiu Xiang; Analisa D Thompson; John T Brogan; Michael L Schulte; Bruce J Melancon; Debbie Mi; L Michelle Lewis; Bende Zou; Liya Yang; Ryan Morrison; Tammy Santomango; Frank Byers; Katrina Brewer; Jonathan S Aldrich; Haibo Yu; Eric S Dawson; Min Li; Owen McManus; Carrie K Jones; J Scott Daniels; Corey R Hopkins; Ximin Simon Xie; P Jeffrey Conn; C David Weaver; Craig W Lindsley
Journal:  ACS Chem Neurosci       Date:  2011-12-21       Impact factor: 4.418

Review 4.  Glycine transporter-1: a new potential therapeutic target for schizophrenia.

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

Review 5.  Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.

Authors:  M A Geyer; K Krebs-Thomson; D L Braff; N R Swerdlow
Journal:  Psychopharmacology (Berl)       Date:  2001-07       Impact factor: 4.530

Review 6.  Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

Authors:  D L Braff; M A Geyer; N R Swerdlow
Journal:  Psychopharmacology (Berl)       Date:  2001-07       Impact factor: 4.530

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

Review 10.  Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain.

Authors:  Robert J Harvey; Benjamin K Yee
Journal:  Nat Rev Drug Discov       Date:  2013-11       Impact factor: 84.694
View more
  3 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.  Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: development of a [3.3.0]-based series and other piperidine bioisosteres.

Authors:  Douglas J Sheffler; Michael T Nedelcovych; Richard Williams; Stephen C Turner; Brittany B Duerk; Megan R Robbins; Sataya B Jadhav; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; R Nathan Daniels; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2014-01-13       Impact factor: 2.823

3.  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
  3 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.