ArticleEuropean journal of medicinal chemistry2018
Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120.
Article in European journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 42 citations in OpenAlex.
- Antiviral Protein-Protein Interaction Inhibitors.Journal of medicinal chemistry · 2024Review
- Antiviral Activity and Crystal Structures of HIV-1 gp120 Antagonists.International journal of molecular sciences · 2022Article
- Identification of human immunodeficiency virus -1 E protein-targeting lead compounds by pharmacophore based screening.Saudi medical journal · 2022Article
- Article
- Small-Molecule HIV Entry Inhibitors Targeting gp120 and gp41.Advances in experimental medicine and biology · 2022Review
- Design of human immunodeficiency virus-1 neutralizing peptides targeting CD4-binding site: An integrative computational biologics approach.Frontiers in medicine · 2022Article
- The Genesis and Future Prospects of Small Molecule HIV-1 Attachment Inhibitors.Advances in experimental medicine and biology · 2022Review
- HIV-1 gp120 Antagonists Also Inhibit HIV-1 Reverse Transcriptase by Bridging the NNRTI and NRTI Sites.Journal of medicinal chemistry · 2021Article
- Design of gp120 HIV-1 entry inhibitors by scaffold hopping via isosteric replacements.European journal of medicinal chemistry · 2021Article
- Pyrroles as Privileged Scaffolds in the Search for New Potential HIV Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Design, synthesis, and antiviral activity of a series of CD4-mimetic small-molecule HIV-1 entry inhibitors.Bioorganic & medicinal chemistry · 2021Article
- Targeting protein-protein interaction interfaces in COVID-19 drug discovery.Computational and structural biotechnology journal · 2021Review
- Facile Synthesis of NH-Free 5-(Hetero)Aryl-Pyrrole-2-Carboxylates by Catalytic C-H Borylation and Suzuki Coupling.Molecules (Basel, Switzerland) · 2020Article
- Preclinical Optimization of gp120 Entry Antagonists as anti-HIV-1 Agents with Improved Cytotoxicity and ADME Properties through Rational Design, Synthesis, and Antiviral Evaluation.Journal of medicinal chemistry · 2020Article
- Rational Design of A Novel Small-Molecule HIV-1 Inactivator Targeting Both gp120 and gp41 of HIV-1.Frontiers in pharmacology · 2020Article
- In Silico Identification of Novel Aromatic Compounds as Potential HIV-1 Entry Inhibitors Mimicking Cellular Receptor CD4.Viruses · 2019Article
- Synthesis, Antiviral Activity, and Structure-Activity Relationship of 1,3-Benzodioxolyl Pyrrole-Based Entry Inhibitors Targeting the Phe43 Cavity in HIV-1 gp120.ChemMedChem · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
We are continuing our concerted effort to optimize our first lead entry antagonist, NBD-11021, which targets the Phe43 cavity of the HIV-1 envelope glycoprotein gp120, to improve antiviral potency and ADMET properties. In this report, we present a structure-based approach that helped us to generate working hypotheses to modify further a recently reported advanced lead entry antagonist, NBD-14107, which showed significant improvement in antiviral potency when tested in a single-cycle assay against a large panel of Env-pseudotyped viruses. We report here the synthesis of twenty-nine new compounds and evaluation of their antiviral activity in a single-cycle and multi-cycle assay to derive a comprehensive structure-activity relationship (SAR). We have selected three inhibitors with the high selectivity index for testing against a large panel of 55 Env-pseudotyped viruses representing a diverse set of clinical isolates of different subtypes. The antiviral activity of one of these potent inhibitors, 55 (NBD-14189), against some clinical isolates was as low as 63 nM. We determined the sensitivity of CD4-binding site mutated-pseudoviruses to these inhibitors to confirm that they target HIV-1 gp120. Furthermore, we assessed their ADMET properties and compared them to the clinical candidate attachment inhibitor, BMS-626529. The ADMET data indicate that some of these new inhibitors have comparable ADMET properties to BMS-626529 and can be optimized further to potential clinical candidates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.