Drug discovery Lipinski's Rule: what is it?

I've really heard that it is very popular 😀 

The Lipinski rule, also known as the rule of five, is an empirical rule that helps determine whether a chemical compound with a certain pharmacological or biological activity has properties that make it an orally active drug for humans.

@benzol00 is it really a RULE, or just some recommendation?

The rule describes the molecular properties that are important for the pharmacokinetics of a drug in the human body, including its absorption, distribution, metabolism, and excretion. However, the rule does not predict whether a compound is pharmacologically active. This rule is important to consider when creating drugs, when a pharmacologically active drug is optimized step by step to increase the activity and selectivity of the compound, as well as to ensure that the physicochemical properties inherent in compounds that obey the Lipinski rule are maintained. Compounds conforming to Lipinski's rule are less intensively consumed during clinical trials and therefore have an increased likelihood of entering the market

Lipinski's rule states that, in general, an orally active drug must violate no more than one of the following conditions:

-No more than 5 donor hydrogen bonds (total number of nitrogen-hydrogen and oxygen-hydrogen bonds);

-No more than 10 acceptor hydrogen bonds (total number of nitrogen or oxygen atoms);

-The molecular weight of the compound is less than 500 amu;

-Octanol-water partition coefficient (log P), must not exceed 5

When considering this rule, I would like to understand why the presence of a certain number of donor and acceptor atoms is so important? why is the distribution in the system chosen exactly H2O-octanol?

@argentum ok, looks like the rule is a first step in Drug Discovery process

@argentum Maybe it is connected with absorption or permeation characteristics? With larger values we will get worse characteristics.

Posted by: @morphism

@benzol00 is it really a RULE, or just some recommendation?

I assume that this is more of a rule, since the recommendations are not mandatory, and it was said above that an orally active drug should violate no more than one of the conditions

@benzol00 ^{intetesting.. Also I'm curious what people from Drug Discovery groups/companies think about the rule🤔}

@morphism 

“The Lipinski Rule (molecular weight <500, not more than five hydrogen bond donors, not more than ten hydrogen bond acceptors and a partition coefficient(log P) value <5) have much to commend but do not need to be slavishly followed for many therapeutic projects. What is most important in the context of quadruplex-binding ligands is to pay especial attention to:”

https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/lipinskis-rule-of-five

@morphism I don't know, but I'd like to hear an exact explanation.

@benzol00 Pay attention to what?)

@argentum Yeah 😔