1,3,5-Trialkyl-2,4,6-triiodobenzenes: novel X-ray contrast agents for gastrointestinal imaging
| Autor: | William F. Blazak, Susan A. Wilson, Kimberly G. Estep, and Andy Spencer, Dinesh Mishra, Illig Carl R, Dennis M. Miller, Jack M. Allen, Bacon Edward R, David Johnson, John L. Toner, Kurt A. Josef |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Chemical Phenomena Radiodensity Radiography chemistry.chemical_element High density Contrast Media In Vitro Techniques Absorption Rats Sprague-Dawley chemistry.chemical_compound Mice Dogs Cricetinae Drug Discovery Animals Humans Mice Inbred ICR Mesocricetus Molecular Structure Chemistry business.industry Chemistry Physical Iodobenzenes X-ray Barium Contrast (music) Anatomy Thyroid Diseases Rats Barium sulfate Kinetics Drug Design Microsomes Liver Molecular Medicine Emulsions Gastrointestinal imaging business Digestive System Biomedical engineering |
| Zdroj: | Journal of medicinal chemistry. 43(10) |
| ISSN: | 0022-2623 |
| Popis: | Examination of the gastrointestinal (GI) tract has been performed for decades using barium sulfate. Although this agent has many recognized limitations including extreme radiopacity, poor intrinsic affinity for the GI mucosa, and very high density, no alternative contrast agents have emerged which produce comparable or better contrast visualization. In fact, the various techniques of the GI radiologic examination (i.e., single contrast, double contrast, 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 barium 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 designed 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-in-water emulsion, was found to be well-tolerated in rodents (mice, hamsters, rats) following acute oral and/or intraperitoneal administrations at 4 times the anticipated human clinical dose. No metabolism of 17 was detected in rat, hamster, dog, monkey, or human hepatic microsomes, suggesting the lack of oral toxicity was a consequence of poor absorption. In imaging experiments in dogs, emulsions of 17 have demonstrated excellent mucosal coating and improved radiodensity relative to barium sulfate suspensions. On the basis of the preliminary imaging and toxicity data, compound 17 was selected as a potential development candidate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|