1,3,5-trialkyl-2,4,6-triiodobenzenes: Novel X-ray contrast agents for gastrointestinal imaging

Examination of the gastrointestinal (GI) tract has been performed for decad es using barium sulfate. Although this agent has many recognized limitation s including extreme radiopacity, poor intrinsic affinity for the GI mucosa, and very high density, no alternative contrast agents have emerged which p roduce comparable or better contrast visualization. In fact, the various te chniques of the GI radiologic examination (i.e., single contrast, double co ntrast, biphasic) were developed to compensate for its limitations. Each of these techniques requires complex patient manipulation to achieve adequate mucosal coating or compression to overcome the marked radiopacity of bariu m sulfate in order to obtain a diagnostically useful examination. A Series of novel radiopaque oils, the 1,3,5-trialkyl-2,4,6-triiodobenzenes, was des igned to improve the efficacy, stability, and safety of barium formulations . These substances were prepared in two steps from 1,3,5-trichlorobenzene. Compound 17 (1,3,5-tri-n-hexyl-2,4,6-triiodobenzene) formulated as an oil-i n-water emulsion, was found to be well-tolerated in rodents (mice, hamsters , rats) following acute oral and/or intraperitoneal administrations at 4 ti mes the anticipated human clinical dose. No metabolism of 17 was detected i n rat, hamster, dog, monkey, or human hepatic microsomes, suggesting the la ck of oral toxicity was a consequence of poor absorption.