ReviewRSC medicinal chemistry2020
Scaffold-hopping as a strategy to address metabolic liabilities of aromatic compounds.
Review in RSC medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- Synthetic strategies and therapeutic insights into FDA-approved indole-containing drugs.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Bicyclo[1.1.1]pentane as a Phenyl Isosteric Replacement.ACS medicinal chemistry letters · 2026Article
- ReLink-PyB: an adapted REINVENT-based framework for non-DSM PfDHODH inhibitor discovery.Scientific reports · 2026Article
- Cytochrome P450-Mediated Metabolism of AntimycobacterialACS infectious diseases · 2026Article
- Hyperpyramidalized alkenes with bond orders near 1.5 as synthetic building blocks.Nature chemistry · 2026Article
- Polynitrogen-containing compounds as multi-target sEH/FAAH inhibitors: Structure-activity relationship and pharmacological studies.Bioorganic & medicinal chemistry · 2026Article
- Identification and Characterization of ERK2 Dimerization Inhibitors by Integrated In Silico and In Vitro Screening.International journal of molecular sciences · 2025Article
- Carbon-to-nitrogen atom swap enables direct access to benzimidazoles from drug-like indoles.Nature chemistry · 2025Article
- Discovery of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 Main Protease through Computer-Aided Drug Design.Journal of medicinal chemistry · 2025Article
- Discovery and Evaluation of Active Site-Directed, Potent, and Selective Sulfophenyl Acetic Amide-Based Inhibitors for the Laforin Phosphatase.Journal of medicinal chemistry · 2025Article
- Computational Investigation of Montelukast and Its Structural Derivatives for Binding Affinity to Dopaminergic and Serotonergic Receptors: Insights from a Comprehensive Molecular Simulation.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- 3D-QSAR, Scaffold Hopping, Virtual Screening, and Molecular Dynamics Simulations of Pyridin-2-one as mIDH1 Inhibitors.International journal of molecular sciences · 2024Article
- Development of Pyridothiophene Compounds for PET Imaging of α-Synuclein.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- The Impact of Inorganic Systems and Photoactive Metal Compounds on Cytochrome P450 Enzymes and Metabolism: From Induction to Inhibition.Biomolecules · 2024Review
- Small Molecule Inhibitors Targeting the "Undruggable" Survivin: The Past, Present, and Future from a Medicinal Chemist's Perspective.Journal of medicinal chemistry · 2023Review
- Systematical Evaluation of the Structure-Cardiotoxicity Relationship of 7-Azaindazole-based PI3K Inhibitors Designed by Bioisosteric Approach.Cardiovascular toxicology · 2023Article
- Covalent Macrocyclic Proteasome Inhibitors Mitigate Resistance inACS infectious diseases · 2023Article
- Oxetane-, Azetidine-, and Bicyclopentane-BearingOrganic letters · 2023Article
- Synthesis and Anticancer Evaluation of Novel 7-Aza-Coumarine-3-Carboxamides.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Understanding and minimizing oxidative metabolism of aromatic compounds is a key hurdle in lead optimization. Metabolic processes not only clear compounds from the body, but they can also transform parent compounds into reactive metabolites. One particularly useful strategy when addressing metabolically labile or oxidation-prone structures is scaffold-hopping. Replacement of an aromatic system with a more electron-deficient ring system can often increase robustness towards cytochrome P450-mediated oxidation while conserving the structural requirements of the pharmacophore. The most common example of this substitution strategy, replacement of a phenyl ring with a pyridyl substituent, is prevalent throughout the literature; however scaffold-hopping encompasses a much wider scope of heterocycle replacement. This review will showcase recent examples where different scaffold-hopping approaches were used to reduce metabolic clearance or block the formation of reactive metabolites. Additionally, we will highlight considerations that should be made to garner the most benefit from a scaffold-hopping strategy for lead optimization.
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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.