It has been suggested that this article or section be merged into Druglikeness. (Discuss)

Lipinski's Rule of Five is a rule of thumb to evaluate druglikeness, or determine if a chemical compound with a certain pharmacological or biological activity has properties that would make it a likely orally active drug in humans. The rule was formulated by Christopher A. Lipinski in 1997, based on the observation that most medication drugs are relatively small and lipophilic molecules.^[1] Wikipedia does not have an article with this exact name. ... It has been suggested that Lipinskis Rule of Five be merged into this article or section. ... A rule of thumb is an easily learned and easily applied procedure for approximately calculating or recalling some value, or for making some determination. ... It has been suggested that Lipinskis Rule of Five be merged into this article or section. ... A chemical compound is a chemical substance of two or more different chemically bonded chemical elements, with a fixed ratio determining the composition. ... Pharmacology (in Greek: pharmakos (φάρμακον) meaning drug, and logos (λόγος) meaning science) is the study of how substances interact with living organisms to produce a change in function. ... It has been suggested that this article or section be merged with Bioactivity. ... For other meanings, see Drug (disambiguation). ... It has been suggested that Blockbuster drug be merged into this article or section. ... ... In science, a molecule is a group of atoms in a definite arrangement held together by chemical bonds. ...

The rule describes molecular properties important for a drug's pharmacokinetics in the human body, including their absorption, distribution, metabolism, and excretion ("ADME"). However, the rule does not predict if a compound is pharmacologically active. This article or section does not cite its references or sources. ... Pharmacokinetics (in Greek: pharmacon meaning drug, and kinetikos meaning putting in motion) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. ... In pharmacology (and more specifically pharmacokinetics), absorption is the movement of a drug into the bloodstream. ... Distribution in pharmacology is a branch of pharmacokinetics describing reversible transfer of drug from one location to another within the body. ... A few of the metabolic pathways in a cell. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... ADME is an acronym in pharmacokinetics and pharmacology for Absorption, Distribution, Metabolism, and Excretion, and describes the disposition of a pharmaceutical compound within an animal or human body. ...

The rule is important for drug development where a pharmacologically active lead structure is optimized step-wise for increased activity and selectivity, as well as drug-like properties as described by Lipinski's rule. The modification of the molecular structure often leads to drugs with higher molecular weight, more rings, more rotatable bonds, and a higher lipophilicity.^[2] It has been suggested that this article or section be merged into Pharmacology. ... Early drug discovery involves several phases from Target identification to preclinical development. ... A chemical bond is the physical process responsible for the attractive interactions between atoms and molecules, and that which confers stability to diatomic and polyatomic chemical compounds. ...

The rule

Lipinski's Rule of Five states that, in general, an orally active drug has:

• Not more than 5 hydrogen bond donors (OH and NH groups)
• Not more than 10 hydrogen bond acceptors (notably N and O)
• A molecular weight under 500 g/mol
• A partition coefficient log P less than 5

The rules have spawned many extensions, for example one from a 1999 paper by Ghose et al.:^[3] An example of a quadruple hydrogen bond between a self-assembled dimer complex reported by Meijer and coworkers. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... A partition coefficient is a measure of differential solubility of a compound in two solvents. ...

• Partition coefficient log P in -0.4 to +5.6 range
• Molar refractivity from 40 to 130
• Molecular weight from 160 to 480
• Number of heavy atoms from 20 to 70

Over the past decade Lipinski's profiling tool for drug-likeness has led to further investigations by scientists to extend profiling tools to lead-like properties of compounds in the hope that a better starting point in early discovery can save time and cost. Molar refractivity is a measure of the volume occupied by an atom or group and is dependent on the temperature, the index of refraction, and the pressure. ...

See also

• QSAR, quantitative structure-activity relationship
• Polar surface area
• Biopharmaceutics Classification System
• Chemical property
• Molecular property
• Physical property
• Chemical structure

QSAR (Quantitative Structure-Activity Relationship, sometimes the A stands also for Affinity=reactivity) is the quantitative correlation of the biological (ecological, toxicological or pharmacological) activity to the structure of chemical compounds, which allows the prediction of the so-called drug efficacy of a structurally related compound. ... The Polar Surface Area (PSA) is defined as the surface sum over all polar atoms, (usually oxygen and nitrogen), including also attached hydrogens. ... This system is a guidance provided by the U.S. Food and Drug Administration [1]. According to the Biopharmaceutics Classification System (BCS_(disambiguation)), drug substances are classified as follows: Class I - High Permeability, High Solubility Class II - High Permeability, Low Solubility Class III - Low Permeability, High Solubility Class IV - Low... The phrase chemical property is context-dependent, but generally refers to a materials behavior at ambient conditions (i. ... This article or section does not cite its references or sources. ... A physical property is any aspect of an object or substance that can be measured or perceived without changing its identity. ... Chemical structure refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. ...

References

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• Interactive Rule of Five calculator
• Free online calculations of Hydrogen bond donor/acceptor, mass and logP using ChemAxon's Marvin and Calculator Plugins - requires Java