Escape from flatland: increasing saturation as an approach to improving clinical success.
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Summary
It is demonstrated that saturation correlates with solubility, an experimental physical property important to success in the drug discovery setting, and both complexity and the presence of chiral centers correlate with success as compounds transition from discovery, through clinical testing, to drugs.
- Type
- article
- Published
- 2009-10-14
- Cited by
- 3,381
- References
- 36
- OpenAlex
- https://openalex.org/W2074274985
- Semantic Scholar
- https://api.semanticscholar.org/CorpusID:5225366
Keywords
Polar surface area, Chemistry, Drug discovery, Solubility, Saturation (graph theory)
References
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- Diversity-oriented synthesis: exploring the intersections between chemistry and biology
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- Cation-π Interactions in Chemistry and Biology: A New View of Benzene, Phe, Tyr, and Trp
- Estimation of the aqueous solubility I: application to organic nonelectrolytes.
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- Revisiting the Rule of Five on the Basis of Pharmacokinetic Data from Rat
- Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease
- The role of ligand efficiency metrics in drug discovery
- Impact of Stereospecific Intramolecular Hydrogen Bonding on Cell Permeability and Physicochemical Properties
- The Purchasable Chemical Space: A Detailed Picture
- Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors.
- Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors.
- Computational analysis of calculated physicochemical and ADMET properties of protein-protein interaction inhibitors
- 2-Formylpyridyl Ureas as Highly Selective Reversible-Covalent Inhibitors of Fibroblast Growth Factor Receptor 4.
- Catalytic C(sp2)-C(sp3) Bond Formation of Methoxyarenes by the Organic Superbase t-Bu-P4.
- Design and Synthesis of Hepatitis C Virus NS3 Protease Inhibitors : Targeting Different Genotypes and Drug-Resistant Variants
- Principal Component Analysis as a Tool for Library Design: A Case Study Investigating Natural Products, Brand-Name Drugs, Natural Product-Like Libraries, and Drug-Like Libraries
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- Discovery of Highly Isoform Selective Thiazolopiperidine Inhibitors of Phosphoinositide 3-Kinase γ.
- Novel benzidine and diaminofluorene prolinamide derivatives as potent hepatitis C virus NS5A inhibitors.
- Cheminformatic comparison of approved drugs from natural product versus synthetic origins
- Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
- Effect of Chirality on Common in Vitro Experiments: An Enantiomeric Pair Analysis.
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