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Literature DB >> 26531151

Core chemotype diversification in the HIV-1 entry inhibitor class using field-based bioisosteric replacement.

Marina Tuyishime¹, Rae Lawrence², Simon Cocklin³.

Abstract

Demand remains for new inhibitors of HIV-1 replication and the inhibition of HIV-1 entry is an extremely attractive therapeutic approach. Using field-based bioisosteric replacements, we have further extended the chemotypes available for development in the HIV-1 entry inhibitor class. Moreover, using field-based disparity analysis of the compounds, 3D structure-activity relationships were derived that will be useful in the further development of these inhibitors towards clinical utility.

Entities: CellLine Chemical Disease Gene Species

Keywords: Antiviral; Bioisosteric replacement; Computer-aided drug design; Field-based; HIV-1 envelope protein; SAR analysis; Scaffold-hopping; Structure–activity landscape

Mesh：

Substances：
Anti-HIV Agents

Year: 2015 PMID： 26531151 PMCID： PMC4684712 DOI： 10.1016/j.bmcl.2015.10.080

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

29 in total

1. Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4.

Authors: Qian Zhao; Liying Ma; Shibo Jiang; Hong Lu; Shuwen Liu; Yuxian He; Nathan Strick; Nouri Neamati; Asim Kumar Debnath
Journal: Virology Date: 2005-09-01 Impact factor: 3.616

2. Novel lead structures for p38 MAP kinase via FieldScreen virtual screening.

Authors: Timothy J Cheeseright; Melanie Holm; Frank Lehmann; Sabine Luik; Marcia Göttert; James L Melville; Stefan Laufer
Journal: J Med Chem Date: 2009-07-23 Impact factor: 7.446

3. Discovery of a small molecule inhibitor through interference with the gp120-CD4 interaction.

Authors: David H Williams; Fiona Adam; David R Fenwick; Juin Fok-Seang; Iain Gardner; Duncan Hay; Rawal Jaiessh; Donald S Middleton; Charles E Mowbray; Tanya Parkinson; Manos Perros; Christopher Pickford; Michelle Platts; Amy Randall; Daniel Siddle; Peter T Stephenson; Thien-Duc Tran; Hannah Vuong
Journal: Bioorg Med Chem Lett Date: 2009-06-25 Impact factor: 2.823

Review 4. High content pharmacophores from molecular fields: a biologically relevant method for comparing and understanding ligands.

Authors: Timothy J Cheeseright; Mark D Mackey; Robert A Scoffin
Journal: Curr Comput Aided Drug Des Date: 2011-09-01 Impact factor: 1.606

5. Molecular field technology applied to virtual screening and finding the bioactive conformation.

Authors: Tim Cheeseright; Mark Mackey Phd; Sally Rose Phd; Andy Vinter Phd
Journal: Expert Opin Drug Discov Date: 2007-01 Impact factor: 6.098

6. Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects.

Authors: Richard E Nettles; Dirk Schürmann; Li Zhu; Michele Stonier; Shu-Pang Huang; Ih Chang; Caly Chien; Mark Krystal; Megan Wind-Rotolo; Neelanjana Ray; George J Hanna; Richard Bertz; Dennis Grasela
Journal: J Infect Dis Date: 2012-08-14 Impact factor: 5.226

7. Design, synthesis, and antiviral activity of entry inhibitors that target the CD4-binding site of HIV-1.

Authors: Francesca Curreli; Spreeha Choudhury; Ilya Pyatkin; Victor P Zagorodnikov; Anna Khulianova Bulay; Andrea Altieri; Young Do Kwon; Peter D Kwong; Asim K Debnath
Journal: J Med Chem Date: 2012-05-10 Impact factor: 7.446

8. Identification of novel small-molecule agonists for human formyl peptide receptors and pharmacophore models of their recognition.

Authors: Liliya N Kirpotina; Andrei I Khlebnikov; Igor A Schepetkin; Richard D Ye; Marie-Josèphe Rabiet; Mark A Jutila; Mark T Quinn
Journal: Mol Pharmacol Date: 2009-11-10 Impact factor: 4.436

9. Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins.

Authors: Zhihai Si; Navid Madani; Jason M Cox; Jason J Chruma; Jeffrey C Klein; Arne Schön; Ngoc Phan; Liping Wang; Alyssa C Biorn; Simon Cocklin; Irwin Chaiken; Ernesto Freire; Amos B Smith; Joseph G Sodroski
Journal: Proc Natl Acad Sci U S A Date: 2004-03-29 Impact factor: 11.205

Review 10. Structure-based design, synthesis and validation of CD4-mimetic small molecule inhibitors of HIV-1 entry: conversion of a viral entry agonist to an antagonist.

Authors: Joel R Courter; Navid Madani; Joseph Sodroski; Arne Schön; Ernesto Freire; Peter D Kwong; Wayne A Hendrickson; Irwin M Chaiken; Judith M LaLonde; Amos B Smith
Journal: Acc Chem Res Date: 2014-02-06 Impact factor: 22.384

8 in total

1. Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action.

Authors: Jimmy P Xu; Ashwanth C Francis; Megan E Meuser; Marie Mankowski; Roger G Ptak; Adel A Rashad; Gregory B Melikyan; Simon Cocklin
Journal: J Drug Des Res Date: 2018-08-13

Review 2. Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment.

Authors: Andrew W Woodham; Joseph G Skeate; Adriana M Sanna; Julia R Taylor; Diane M Da Silva; Paula M Cannon; W Martin Kast
Journal: AIDS Patient Care STDS Date: 2016-07 Impact factor: 5.078

Core chemotype diversification in the HIV-1 entry inhibitor class using field-based bioisosteric replacement.

1. Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4.

2. Novel lead structures for p38 MAP kinase via FieldScreen virtual screening.

3. Discovery of a small molecule inhibitor through interference with the gp120-CD4 interaction.

Review 4. High content pharmacophores from molecular fields: a biologically relevant method for comparing and understanding ligands.

5. Molecular field technology applied to virtual screening and finding the bioactive conformation.

6. Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects.

7. Design, synthesis, and antiviral activity of entry inhibitors that target the CD4-binding site of HIV-1.

8. Identification of novel small-molecule agonists for human formyl peptide receptors and pharmacophore models of their recognition.

9. Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins.

Review 10. Structure-based design, synthesis and validation of CD4-mimetic small molecule inhibitors of HIV-1 entry: conversion of a viral entry agonist to an antagonist.

1. Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action.

Review 2. Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment.

Review 3. The Genesis and Future Prospects of Small Molecule HIV-1 Attachment Inhibitors.

4. Clade-Specific Alterations within the HIV-1 Capsid Protein with Implications for Nuclear Translocation.

5. Field-Based Affinity Optimization of a Novel Azabicyclohexane Scaffold HIV-1 Entry Inhibitor.

6. Network Analysis Guided Designing of Multi-Targeted Anti-Fungal Agents: Synthesis and Biological Evaluation.

7. Kinetic Characterization of Novel HIV-1 Entry Inhibitors: Discovery of a Relationship between Off-Rate and Potency.

8. Composition and Orientation of the Core Region of Novel HIV-1 Entry Inhibitors Influences Metabolic Stability.