The solubility of 11 new drug-like spiro-compounds in buffer solution (pH 7.4) and hexane was measured by the isothermal saturation technique in the temperature range of (293 to 315) K. The influence of substituent chemical nature, branching of aliphatic chain, and inclusion of oxygen and halogen atoms in molecule structure were investigated. The correlation dependences of the solubility on molecular descriptors and thermophysical properties were estimated. Standard thermodynamic solubility functions for the test compounds were calculated. The conclusion reveals the dominant contribution of dispersion forces in the solution process.