The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space
Abstract
Utilising ‘beyond rule of five’ chemical space is becoming increasingly important in drug design, but is usually at odds with good oral absorption. The formation of intramolecular hydrogen bonds in drug molecules is hypothesised to shield polarity facilitating improved membrane permeability and intestinal absorption. NMR based evidence for intramolecular hydrogen bonding in several ‘beyond rule of five’ oral drugs is described. Furthermore, the propensity for these drugs to form intramolecular hydrogen bonds could be predicted for through modelling the lowest energy conformation in the gas phase. The modulation of apparent lipophilicity through intramolecular hydrogen bonding in these molecules is supported by intrinsic cell permeability and intestinal absorption data in rat and human.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,385
Molecular properties that influence the oral bioavailability of drug candidates
Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020017n · Cited by 8,420
Can the pharmaceutical industry reduce attrition rates?
Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167
Ertl, P., Rohde, B., & Selzer, P. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm000942e · Cited by 3,084
The influence of drug-like concepts on decision-making in medicinal chemistry
Leeson, P. D., & Springthorpe, B. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2445 · Cited by 2,403
Small-molecule inhibitors of protein–protein interactions: progressing towards the dream
Arkin, M. R., & Wells, J. A. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1343 · Cited by 1,705
Physiochemical drug properties associated with in vivo toxicological outcomes
Hughes, J. D., Blagg, J., Price, D. A., Bailey, S., DeCrescenzo, G. A., Devraj, R. V., Ellsworth, E., Fobian, Y. M., Gibbs, M. E., Gilles, R. W., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.071 · Cited by 946
Global mapping of pharmacological space
Paolini, G. V., Shapland, R. H. B., van Hoorn, W. P., Mason, J. S., & Hopkins, A. L. (2006) · Nature Biotechnology · doi:10.1038/nbt1228 · Cited by 811
Polar Molecular Surface Properties Predict the Intestinal Absorption of Drugs in Humans
Palm, K., Stenberg, P., Luthman, K., & Artursson1, P. (1997) · Pharmaceutical Research · doi:10.1023/a:1012188625088 · Cited by 756
Intramolecular Hydrogen Bonding in Medicinal Chemistry
Kuhn, B., Mohr, P., & Stahl, M. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100087s · Cited by 571
Cited by
Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design
Meanwell, N. A. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01788 · Cited by 2,655
Macrocyclic Peptides as Drug Candidates: Recent Progress and Remaining Challenges
Vinogradov, A. A., Yin, Y., & Suga, H. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b13178 · Cited by 848
Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates
Doak, B. C., Over, B., Giordanetto, F., & Kihlberg, J. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.08.013 · Cited by 835
Strategic Approaches to Optimizing Peptide ADME Properties
Di, L. (2015) · The AAPS Journal · doi:10.1208/s12248-014-9687-3 · Cited by 669
Finding the sweet spot: the role of nature and nurture in medicinal chemistry
Hann, M. M., & Keserü, G. M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3701 · Cited by 411
Metadata
- Authors
- Alex, A., Millan, D. S., Perez, M., Wakenhut, F., & Whitlock, G. A.
- Venue
- MedChemComm
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2011
- Volume
- 2
- Issue
- 7
- Pages
- 669
- ISSN
- 2040-2503 (ISSN-L)
- 2040-2511
- OpenAlex
- W2072631488
- Cited by
- 329
- References
- 27
- FWCI
- 14.35
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space. https://app.cochat.ai/papers/10.1039/c1md00093d
- The paper
- Alex, A., Millan, D. S., Perez, M., Wakenhut, F., & Whitlock, G. A. (2011). Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space. MedChemComm. https://doi.org/10.1039/c1md00093d
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
