Highlights•NRot and Φ are flexibility indexes suitable for early drug discovery metrics.•In the
bRo5 chemical space NRot and Φ are not interchangeable.•In the presence of macrocycles …

An increasing number of drug discovery programs concern compounds in the beyond rule of
5 (bRo5) chemical space, such as cyclic peptides, macrocycles, and degraders. Recent …

The rule of 5 (Ro5) is a set of in silico guidelines applied to drug discovery to prioritize
compounds with an increased likelihood of high oral absorption. It has been influential in …

To improve discovery of drugs for difficult targets, the opportunities of chemical space
beyond the rule of 5 (bRo5) were examined by retrospective analysis of a comprehensive …

The pharmacokinetic and safety profiles of clinical drug candidates are greatly influenced by
their requisite physicochemical properties. In particular, it has been shown that 2D molecular …

Twenty five years ago, Christopher Lipinski and colleagues published arguably the most
influential sentence in small-molecule drug discovery. Their cleverly crafted 'rule of 5'(Ro5) …

A new molecular descriptor, nConf20, based on chemical connectivity, is presented which
captures the accessible conformational space of a molecule. Currently the best available …

The paradigm of “drug-like-ness” dramatically altered the behavior of the medicinal
chemistry community for a long time. In recent years, scientists have empirically found a …

The concept of drug-likeness helps to optimise pharmacokinetic and pharmaceutical
properties, for example, solubility, chemical stability, bioavailability and distribution profile. A …

The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with
structural limitations in protein targets and the drug target ligands. Three of four parameters …