QSAR-based solubility model for drug-like compounds.

Bioorganic & medicinal chemistry (2010-09-03)
Rafael Gozalbes, Antonio Pineda-Lucena
ABSTRACT

Solubility plays a very important role in the selection of compounds for drug screening. In this context, a QSAR model was developed for predicting water solubility of drug-like compounds. First, a set of relevant parameters for establishing a drug-like chemical space was defined. The comparison of chemical structures from the FDAMDD and PHYSPROP databases allowed the selection of properties that were more efficient in discriminating drug-like compounds from other chemicals. These filters were later on applied to the PHYSPROP database and 1174 chemicals fulfilling these criteria and with experimental solubility information available at 25°C were retained. Several QSAR solubility models were developed from this set of compounds, and the best one was selected based on the accuracy of correct classifications obtained for randomly chosen training and validation subsets. Further validation of the model was performed with a set of 102 drugs for which experimental solubility data have been recently reported. A good agreement between the predictions and the experimental values confirmed the reliability of the QSAR model.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Salicylic acid, ACS reagent, ≥99.0%
Sigma-Aldrich
Ciprofloxacin, ≥98% (HPLC)
Sigma-Aldrich
5-Fluorouracil, ≥99% (HPLC), powder
Sigma-Aldrich
Thymol, ≥98.5%
Sigma-Aldrich
1-Naphthol, ReagentPlus®, ≥99%
Sigma-Aldrich
Amoxicillin, potency: ≥900 μg per mg
Sigma-Aldrich
Guanine, 98%
Sigma-Aldrich
Salicylic acid, suitable for plant cell culture
Sigma-Aldrich
Nalidixic acid, ≥98%
Sigma-Aldrich
4-Hydroxybenzoic acid, ReagentPlus®, ≥99%
Sigma-Aldrich
Lidocaine, powder
Sigma-Aldrich
Ethyl 4-aminobenzoate, 98%
Sigma-Aldrich
Levofloxacin, 98.0-102.0% anhydrous basis (HPLC)
Sigma-Aldrich
4-Hydroxybenzoic acid, ReagentPlus®, 99%
Sigma-Aldrich
Benzocaine, ≥99% (HPLC)
Sigma-Aldrich
Salicylic acid, puriss. p.a., ≥99.0% (T)
Sigma-Aldrich
Tryptamine, ≥97%
Sigma-Aldrich
Salicylic acid, ≥99%, FG
Sigma-Aldrich
Phthalic acid, ACS reagent, ≥99.5%
Sigma-Aldrich
Thymol, meets analytical specification of Ph. Eur., BP, NF, 99-101%
Sigma-Aldrich
Ofloxacin, fluoroquinolone antibiotic
Sigma-Aldrich
Furosemide
Sigma-Aldrich
Salicylic acid, BioXtra, ≥99.0%
Sigma-Aldrich
Enrofloxacin, ≥99.0% (HPLC)
Sigma-Aldrich
Ketoprofen, ≥98% (TLC)
Supelco
Warfarin, analytical standard
Supelco
Norfloxacin, analytical standard, ≥98% (TLC)
Sigma-Aldrich
Sulfamethazine, 99.0-101.0% (on dried basis)
Sigma-Aldrich
4-Iodophenol, 99%
Sigma-Aldrich
(1R,2S)-(−)-Ephedrine, 98%