New nonionic triiodinated x-ray contrast media containing the N-(2-hydroxyethyl)aminopropane-2,3-diol side chain

We have found the amino alcohol (HE)APD to be an effective solubilizing and detoxifying agent for triiodinated benzene XRCM. Most of the compounds containing the (HE)APD moiety displayed good solution properties (low osmolality and viscosity) and relatively low toxicities. A general trend was observed in which compounds with low hydrophilicity were more toxic. High hydrophilicity was found to be necessary for low intracisternal toxicity, but is not the only criterion. Use of the 5-glycolamido group provides compounds with high hydrophilicity. When all the properties were compared, the best compounds in this study were found to be the three asymmetrically substituted isophthalamides containing the (HE)APD and APD side chains (4a-c: MP-1556, MP-1683, and MP-1689). These compounds have excellent solution properties (low osmolality and viscosity) and low intravenous and intracisternal toxicities, and compare favorably to current clinical agents.