ArticleJournal of medicinal chemistry2014
Impact of stereospecific intramolecular hydrogen bonding on cell permeability and physicochemical properties.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
21 citing papers in PubMed.
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Diastereomeric Branched-Ester dBET1 Analogs Exhibit Conformation-Dependent Differences in Passive Membrane Permeability.Journal of medicinal chemistry · 2026Article
- Challenges of Aufheben to Promote Druglikeness: Chemical Modification Strategies to Improve Aqueous Solubility and Permeability.Journal of medicinal chemistry · 2025Review
- Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review.Molecules (Basel, Switzerland) · 2025Review
- Molecular chameleons in drug discovery.Nature reviews. Chemistry · 2024Review
- Addressing Challenges of Macrocyclic Conformational Sampling in Polar and Apolar Solvents: Lessons for Chameleonicity.Journal of chemical information and modeling · 2023Article
- Conformational Sampling Deciphers the Chameleonic Properties of a VHL-Based Degrader.Pharmaceutics · 2023Article
- Article
- Efficient Crystal Structure Prediction for Structurally Related Molecules with Accurate and Transferable Tailor-Made Force Fields.Journal of chemical theory and computation · 2022Article
- Synthesis of New AIEE-Active Chalcones for Imaging of Mitochondria in Living Cells and Zebrafish In Vivo.International journal of molecular sciences · 2021Article
- Article
- Cell Permeability of Isomeric Macrocycles: Predictions and NMR Studies.ACS medicinal chemistry letters · 2021Article
- In vitro binding affinity vs. in vivo site occupancy: A PET study of four diastereomers of dihydrotetrabenazine (DTBZ) in monkey brain.Nuclear medicine and biology · 2021Article
- Connecting the conformational behavior of cyclic octadepsipeptides with their ionophoric property and membrane permeability.Organic & biomolecular chemistry · 2020Article
- Rational Design for Multicolor Flavone-Based Fluorophores with Aggregation-Induced Emission Enhancement Characteristics and Applications in Mitochondria-Imaging.Molecules (Basel, Switzerland) · 2018Article
- Modulation of Oral Bioavailability and Metabolism for Closely Related Cyclic Hexapeptides.International journal of peptide research and therapeutics · 2018Article
- High throughput methods to measure the propensity of compounds to form intramolecular hydrogen bonding.MedChemComm · 2017Review
- Molecular Properties of Drugs Interacting with SLC22 Transporters OAT1, OAT3, OCT1, and OCT2: A Machine-Learning Approach.The Journal of pharmacology and experimental therapeutics · 2016Article
- Stereochemistry Balances Cell Permeability and Solubility in the Naturally Derived Phepropeptin Cyclic Peptides.ACS medicinal chemistry letters · 2016Article
- Focusing on shared subpockets - new developments in fragment-based drug discovery.Expert opinion on drug discovery · 2015Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Profiling of eight stereoisomeric T. cruzi growth inhibitors revealed vastly different in vitro properties such as solubility, lipophilicity, pKa, and cell permeability for two sets of four stereoisomers. Using computational chemistry and NMR spectroscopy, we identified the formation of an intramolecular NH→NR3 hydrogen bond in the set of stereoisomers displaying lower solubility, higher lipophilicity, and higher cell permeability. The intramolecular hydrogen bond resulted in a significant pKa difference that accounts for the other structure-property relationships. Application of this knowledge could be of particular value to maintain the delicate balance of size, solubility, and lipophilicity required for cell penetration and oral administration for chemical probes or therapeutics with properties at, or beyond, Lipinski's rule of 5.
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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.