Literature DB >> 22071305

Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors.

Gary Tresadern1, Francisca Delgado, Oscar Delgado, Harrie Gijsen, Gregor J Macdonald, Dieder Moechars, Frederik Rombouts, Richard Alexander, John Spurlino, Michiel Van Gool, Juan Antonio Vega, Andrés A Trabanco.   

Abstract

Aminopiperazinone inhibitors of BACE were identified by rational design. Structure based design guided idea prioritization and initial racemic hit 18a showed good activity. Modification in decoration and chiral separation resulted in the 40 nM inhibitor, (-)-37, which showed in vivo reduction of amyloid beta peptides. The crystal structure of 18a showed a binding mode driven by interaction with the catalytic aspartate dyad and distribution of the biaryl amide decoration towards S1 and S3 pockets.
Copyright © 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID： 22071305     DOI： 10.1016/j.bmcl.2011.10.050

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


  6 in total

1.  Creation of Novel Cores for β-Secretase (BACE-1) Inhibitors: A Multiparameter Lead Generation Strategy.

Authors:  Jenny Viklund; Karin Kolmodin; Gunnar Nordvall; Britt-Marie Swahn; Mats Svensson; Ylva Gravenfors; Fredrik Rahm
Journal:  ACS Med Chem Lett       Date:  2014-02-03       Impact factor: 4.345

2.  Evaluation of a Series of β-Secretase 1 Inhibitors Containing Novel Heteroaryl-Fused-Piperazine Amidine Warheads.

Authors:  Daniel Oehlrich; Aldo Peschiulli; Gary Tresadern; Michiel Van Gool; Juan Antonio Vega; Ana Isabel De Lucas; Sergio A Alonso de Diego; Hana Prokopcova; Nigel Austin; Sven Van Brandt; Michel Surkyn; Michel De Cleyn; Ann Vos; Frederik J R Rombouts; Gregor Macdonald; Dieder Moechars; Harrie J M Gijsen; Andrés A Trabanco
Journal:  ACS Med Chem Lett       Date:  2019-07-02       Impact factor: 4.345

Review 3.  The structural evolution of β-secretase inhibitors: a focus on the development of small-molecule inhibitors.

Authors:  Stefania Butini; Simone Brogi; Ettore Novellino; Giuseppe Campiani; Arun K Ghosh; Margherita Brindisi; Sandra Gemma
Journal:  Curr Top Med Chem       Date:  2013       Impact factor: 3.295

4.  Development of 2-aminooxazoline 3-azaxanthene β-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D.

Authors:  Jonathan D Low; Michael D Bartberger; Kui Chen; Yuan Cheng; Mark R Fielden; Vijay Gore; Dean Hickman; Qingyian Liu; E Allen Sickmier; Hugo M Vargas; Jonathan Werner; Ryan D White; Douglas A Whittington; Stephen Wood; Ana E Minatti
Journal:  Medchemcomm       Date:  2017-04-27       Impact factor: 3.597

5.  Fragment Binding to β-Secretase 1 without Catalytic Aspartate Interactions Identified via Orthogonal Screening Approaches.

Authors:  Frederik J R Rombouts; Richard Alexander; Erna Cleiren; Alex De Groot; Michel Carpentier; Joyce Dijkmans; Katleen Fierens; Stefan Masure; Diederik Moechars; Martina Palomino-Schätzlein; Antonio Pineda-Lucena; Andrés A Trabanco; Daan Van Glabbeek; Ann Vos; Gary Tresadern
Journal:  ACS Omega       Date:  2017-02-24

6.  Repurposing food molecules as a potential BACE1 inhibitor for Alzheimer's disease.

Authors:  Nobendu Mukerjee; Anubhab Das; Rahul D Jawarkar; Swastika Maitra; Padmashree Das; Melvin A Castrosanto; Soumyadip Paul; Abdul Samad; Magdi E A Zaki; Sami A Al-Hussain; Vijay H Masand; Mohammad Mehedi Hasan; Syed Nasir Abbas Bukhari; Asma Perveen; Badrah S Alghamdi; Athanasios Alexiou; Mohammad Amjad Kamal; Abhijit Dey; Sumira Malik; Ravindra L Bakal; Adel Mohammad Abuzenadah; Arabinda Ghosh; Ghulam Md Ashraf
Journal:  Front Aging Neurosci       Date:  2022-08-22       Impact factor: 5.702
  6 in total

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