Structure–activity relationships for novel drug precursor N-substituted-6-acylbenzothiazolon derivatives: A theoretical approach

• Structure–activity relationships for novel drug precursor 6-acylbenzothiazolon derivatives are researched.
• Vm, MR, ω, EA, EHOMO − ELUMO (ΔE), HOF, χ, μ, S and η parameters give good correlations with log P.
• The electronic structures of 6-acylbenzothiazolon derivatives have been expounded.
• Molecular polarity, hydrophilic character and dipole moment show the same trend.

In this study, the twelve new modeled N-substituted-6-acylbenzothiazolon derivatives having analgesic analog structure have been investigated by quantum chemical methods using a lot of electronic parameters and structure–activity properties; such as molecular polarizability (α), dipole moment (μ), EHOMO, ELUMO, q−, qH+, molecular volume (Vm), ionization potential (IP), electron affinity (EA), electronegativity (χ), molecular hardness (η), molecular softness (S), electrophilic index (ω), heat of formation (HOF), molar refractivity (MR), octanol–water partition coefficient (log P), thermochemical properties (entropy (S), capacity of heat (Cv)); as to investigate activity relationships with molecular structure. The correlations of log P with Vm, MR, ω, EA, EHOMO − ELUMO (ΔE), HOF in aqueous phase, χ, μ, S, η parameters, respectively are obtained, while the linear relation of log P with IP, Cv, HOF in gas phase are not observed. The log P parameter is obtained to be depending on different properties of compounds due to their complexity.