in −0.4 to +5.6 range Molar refractivity from 40 to 130 Molecular weight from 180 to 480 Number of atoms from 20 to 70 (includes H-bond donors [e.g. OHs and NHs] and H-bond acceptors [e.g. Ns and Os]) Veber's Rule further questions a 500 molecular weight cutoff. The polar surface area and the number of rotatable bonds has been found to better discriminate between compounds that are orally active and those that are not for a large data set of compounds. In particular, compounds which meet only the two criteria of: 10 or fewer rotatable bonds and Polar surface area no greater than 140 Å2 are predicted to have good oral bioavailability. Lead-like During drug discovery, lipophilicity and molecular weight are often increased in order to improve the affinity and selectivity of the drug candidate. Hence it is often difficult to maintain drug-likeness (i.e., RO5 compliance) during hit and lead optimization. Hence it has been proposed that members of screening libraries from which hits are discovered should be biased toward lower molecular weight and lipophility so that medicinal chemists will have an easier time in delivering optimized drug development candidates that are also drug-like. Hence the rule of five has been extended to the rule of three (RO3) for defining lead-like compounds. A rule of three compliant compound is defined as one that has: octanol-water partition coefficient log P not greater than 3 molecular mass less than 300 daltons not more than 3 hydrogen bond donors not more than 3 hydrogen bond acceptors not more than 3 rotatable bonds See also Biopharmaceutics Classification System Chemical structure Fragment-based lead discovery QSAR References 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 Calculation of Druglikeness – requires Java Medicinal chemistry Pharmaceutical industry Cheminformatics Drug discovery Rules of thumb