Online citations, reference lists, and bibliographies.
← Back to Search

Experimental And Computational Approaches To Estimate Solubility And Permeability In Drug Discovery And Development Settings.

C. Lipinski, F. Lombardo, B. W. Dominy, P. Feeney
Published 2001 · Medicine
Referenced 1 time by Citationsy Users

Cite This
Download PDF
Analyze on Scholarcy
Share
Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described. In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP > 4.15). Computational methodology for the rule-based Moriguchi Log P (MLogP) calculation is described. Turbidimetric solubility measurement is described and applied to known drugs. High throughput screening (HTS) leads tend to have higher MWT and Log P and lower turbidimetric solubility than leads in the pre-HTS era. In the development setting, solubility calculations focus on exact value prediction and are difficult because of polymorphism. Recent work on linear free energy relationships and Log P approaches are critically reviewed. Useful predictions are possible in closely related analog series when coupled with experimental thermodynamic solubility measurements.
This paper references
10.1021/AR00046A004
Are Crystal Structures Predictable
A. Gavezzotti (1994)
10.1016/0045-6535(90)90142-G
Estimation of aqueous solubility and melting point of PCB congeners
R. Abramowitz (1990)
acetic acids by theoretical deacripton
Ruelle (1994)
10.1007/BF00129753
Development of an automatic estimation system for both the partition coefficient and aqueous solubility
T. Suzuki (1991)
10.1002/JPS.2600690814
Solubility and partitioning I: Solubility of nonelectrolytes in water.
S. Yalkowsky (1980)
10.1002/CHIN.199441232
Prediction of Aqueous Solubility of Organic Compounds
Todd M. Nelson (1994)
Diffusion of small
B. E. Cohen (1972)
10.1038/236173A0
Diffusion of Small Non-Electrolytes across Liposome Membranes
B. Cohen (1972)
10.1007/BF02311772
The use of characteristic volumes to measure cavity terms in reversed phase liquid chromatography
M. H. Abraham (1987)
Estimation of the solubility of complex organic compounds
Yalkowski. S.H (1993)
10.1021/JO00023A045
Correlations between the solvent hydrogen-bond-donating parameter .alpha. and the calculated molecular surface electrostatic potential
J. S. Murray (1991)
10.1002/JPS.2600810924
A new method for the estimation of the aqueous solubility of organic compounds.
N. Bodor (1992)
10.1080/10629369308029892
Molecular Symmetry and Related Properties
R. Dannenfelser (1993)
Scales of solute hydrogen-bonding
gton (1993)
Comparison of log P values for drugs calculated by several methods
J. Leo.A. (1994)
10.1109/IEMBS.1989.96515
Using theoretical descriptors in quantitative structure activity relationships
G.R. Famini (1989)
10.1039/CS9932200073
Scales of solute hydrogen-bonding: their construction and application to physicochemical and biochemical processes
M. Abraham (1993)
10.1016/1359-6446(96)10020-9
Design principles for orally bioavailable drugs
M. A. Navia (1996)
Lipophilicity in molecular modelling
B. Testa (1996)
Calculating log Pact from structures
R. Abramovitz (1993)
10.1016/0045-6535(95)00026-5
AQUAFAC 3: aqueous functional group activity coefficients; application to the estimation of aqueous solubility
P. Myrdal (1995)
10.1248/CPB.43.512
Critique of Recent Comparison of log P Calciulation Methods
A. Leo (1995)
10.1016/S0065-7743(08)60903-3
Chapter 33. Recent Advances in the Generation of Molecular Diversity
W. Moos (1993)
10.1002/MED.2610150202
In vitro systems for studying intestinal drug absorption
K. M. Hillgren (1995)
10.1021/CEN-V072N006.P020
Combinatorial Approaches Provide Fresh Leads for Medicinal Chemistry
R. Baum (1994)
10.1021/JO00077A028
Octanol/water partition coefficients expressed in terms of solute molecular surface areas and electrostatic potentials
T. Brinck (1993)
10.1248/CPB.40.127
Simple Method of Calculating Octanol/Water Partition Coefficient.
I. Moriguchi (1992)
10.1021/JA00025A009
Neural network studies. 1. Estimation of the aqueous solubility of organic compounds
N. Bodor (1991)
10.1248/CPB.42.976
Comparison of Reliability of log P Values for Drugs Calculated by Several Methods
I. Moriguchi (1994)
10.1002/3527601791
Solvents and Solvent Effects in Organic Chemistry
C. Reichardt (1988)
Biologically relevant UV-based solubility assays
C. A. Lipinski (1994)
10.1038/234491c0
Hydrogen Bonding
N. Sheppard (1971)
10.1021/JO00011A060
Correlations between the solvent hydrogen bond acceptor parameter β and the calculated molecular electrostatic potential
J. S. Murray (1991)
Transport of Small Molecules
G. Cooper (2000)
10.1002/QSAR.19940130103
A non-aqueous partitioning system for predicting the oral absorption potential of peptides
D. Paterson (1994)
10.1002/POC.610061204
Hydrogen bonding. 31. Construction of a scale of solute effective or summation hydrogen‐bond basicity
M. Abraham (1993)
A new predictive equation for the solubdity of drugs
P. Ruelle (1991)
10.1021/ci00026a009
Using Backpropagation Networks for the Estimation of Aqueous Activity Coefficients of Aromatic Organic Compounds
Hsiao-Hui Chow (1995)
10.1021/JO00105A020
Analysis of Solute/Solvent Interactions for the Acidity of Acetic Acids by Theoretical Descriptors
A. Headley (1994)
10.1002/CHIN.199607322
Strategies and recent technologies in drug discovery.
H. Kubinyi (1995)
Simple method of calculating octanoll
I. Moriguchi (1992)
10.1002/JPS.2600830915
Hydrogen bonding. 33. Factors that influence the distribution of solutes between blood and brain.
M. Abraham (1994)
10.1021/JM00378A021
Functional group contributions to drug-receptor interactions.
P. Andrews (1984)
10.1002/JPS.2600830806
Hydrogen bonding. 32. An analysis of water-octanol and water-alkane partitioning and the delta log P parameter of seiler.
M. Abraham (1994)
10.1016/0378-5173(94)90187-2
Prediction of carbazole solubility and its dependence upon the solvent nature
P. Ruelle (1994)
10.1016/1359-6446(96)89062-3
Applications of small-molecule combinatorial chemistry to drug discovery
D. Patel (1996)
10.1016/0169-409X(95)00003-P
Transport of small molecules through the blood-brain barrier: biology and methodology
W. Pardridge (1995)



This paper is referenced by
10.3390/molecules25040985
Design, Synthesis, and In Vitro Evaluation of Hydroxybenzimidazole-Donepezil Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease
S. Chaves (2020)
10.3389/fphar.2018.00710
A Method for Rapid Screening of Anilide-Containing AMPK Modulators Based on Computational Docking and Biological Validation
S. Mok (2018)
10.1186/s13321-020-00427-6
SIME: synthetic insight-based macrolide enumerator to generate the V1B library of 1 billion macrolides
P. P. Zin (2020)
10.1371/journal.pone.0055889
Identification of PPARgamma Partial Agonists of Natural Origin (II): In Silico Prediction in Natural Extracts with Known Antidiabetic Activity
L. Guasch (2013)
10.1504/IJCBDD.2013.052200
Multi-view spectral clustering and its chemical application
Adeshola A. Adefioye (2013)
10.1021/ACS.OPRD.7B00087
Process Analytical Tools To Control Polymorphism and Particle Size in Batch Crystallization Processes
T. B. Hansen (2017)
10.15835/NBHA48311986
Pharmacological and ADMET-based pharmacokinetic properties of Syzygium samarangense var. parviflorum leaf extract in in vitro, in vivo and in silico models
Rahni Hossain (2020)
10.1155/2011/483869
Development of Novel In Silico Model to Predict Corneal Permeability for Congeneric Drugs: A QSPR Approach
Charu Sharma (2011)
10.1111/j.1469-8137.2009.03045.x
Plant chemical genetics.
P. McCourt (2010)
Translational research into oral colon-specific drug delivery
R. Schellekens (2011)
10.14499/INDONESIANJPHARM27ISS2PP92
SYNTHESIS AND SCREENING OF SOME AZOMETHINES BEARING METHYL SALICYLATE MOIETY FOR ANTIBACTERIAL ACTIVITIES
S. Baluja (2016)
Transporter-targeted prodrug delivery to improve oral bioavailability of saquinavir
Zhiying Wang (2013)
EFFECT OF SOLVENTS ON PARTICLE SIZE OF ACECLOFENAC NANOSUSPENSION PREPARED BY BOTTOM UP TECHNIQUE
Shivkant Sharma (2015)
10.1002/CHIN.200035229
Estimation of Aqueous Solubility for a Diverse Set of Organic Compounds Based on Molecular Topology.
J. Huuskonen (2010)
10.46624/ajphr.2019.v7.i8.002
The Design of Novel Protein Kinase Inhibitors Using the Naturally Occurring Isojacareubin Scaffold As A Lead
Jeanelle Caruana (2019)
10.1007/s12539-016-0156-9
Identification of Structurally Diverse Antimicrobials Through Sequential Application of Pharmacophore Modeling, Virtual Screening, Molecular Docking and In Vitro Microbiological Assay
R. Mishra (2016)
10.1007/s42250-020-00161-4
Computational Modeling and Pharmacokinetics/ADMET Study of Some Arylpiperazine Derivatives as Novel Antipsychotic Agents Targeting Depression
Sabitu Babatunde Olasupo (2020)
10.3390/ijms19051387
Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
Dahae Lee (2018)
10.1007/s11030-013-9447-9
Classification of Plasmodium falciparum glucose-6-phosphate dehydrogenase inhibitors by support vector machine
X. Hou (2013)
10.1016/j.xphs.2017.09.030
Predicting Solubility/Miscibility in Amorphous Dispersions: It Is Time to Move Beyond Regular Solution Theories.
B. D. Anderson (2018)
10.1093/toxsci/kfx260
Toxicokinetics of Deltamethrin: Dosage Dependency, Vehicle Effects, and Low-Dose Age-Equivalent Dosimetry in Rats
Tanzir B. Mortuza (2018)
10.1111/cbdd.12625
New Eugenol Glucoside‐based Derivative Shows Fungistatic and Fungicidal Activity against Opportunistic Candida glabrata
Thiago Belarmino Souza (2016)
10.24355/DBBS.084-202002131227-0
Synthese und bioanalytische Evaluierung neuer Ruthenium(II) N-heterozyklischer Carben-Komplexe als potenzielle Chemotherapeutika
H. Burmeister (2020)
10.1007/s10822-017-0037-2
Two-track virtual screening approach to identify both competitive and allosteric inhibitors of human small C-terminal domain phosphatase 1
H. Park (2017)
10.3109/1061186X.2015.1132224
Physicochemical property profile for brain permeability: comparative study by different approaches
O. Raevsky (2016)
10.3109/14756366.2013.866660
Carbonic anhydrase inhibition by 1-aroyl-3-(4-aminosulfonylphenyl)thioureas
A. Saeed (2014)
10.1186/s13321-017-0203-5
ExCAPE-DB: an integrated large scale dataset facilitating Big Data analysis in chemogenomics
Jiangming Sun (2017)
10.1016/j.bmcl.2017.04.021
Discovery of indazole aldosterone synthase (CYP11B2) inhibitors as potential treatments for hypertension.
Scott B. Hoyt (2017)
10.4155/fmc-2016-0237
Design, synthesis, molecular modeling and anticholinesterase activity of benzylidene-benzofuran-3-ones containing cyclic amine side chain.
F. Mehrabi (2017)
10.3390/molecules191118057
Synthesis and Biological Evaluation of Liguzinediol Mono- and Dual Ester Prodrugs as Promising Inotropic Agents
J. Zhang (2014)
10.3390/molecules23071550
In Silico Screening of Isocitrate Lyase for Novel Anti-Buruli Ulcer Natural Products Originating from Africa
Samuel K. Kwofie (2018)
10.1007/s12975-016-0518-y
The High Cost of Stroke and Stroke Cytoprotection Research
P. Lapchak (2016)
See more
Semantic Scholar Logo Some data provided by SemanticScholar