Pitrè D, Felder E
Invest Radiol. 1980 Nov-Dec;15(6 Suppl):S301-9. doi: 10.1097/00004424-198011001-00065.
A series of 5-hydroxyacylamino-2,4,6-triiodo-N,N'-hydroxy-alkyl-isophtalamides was prepared in order to study the structural requirements for high water solubility and low toxicity. Among the amides substituted by 2-hydroxyethyl; 2,3-dihydroxypropyl; 1,3-dihydroxypropyl-; and 1,1-dihydroxy-methyl-2-oxyethyl- groups, the highest water solubility was obtained with the 1,3-dihydroxypropyl- group. Neither optical resolution of the 2,3-dihydroxypropyl moiety nor amide formation with two different amines improved the water solubility. The optimal solubility was obtained with S-5-alpha-hydroxypropionylamino-2,4,6-triiodoisophtalic acid di-(1,3-dihydroxy-2-propylamide), iopamidol. Iopamidol forms anhydrous and monohydrate crystals, characterized by differential thermal analyses, x-ray diffraction patterns, and solubility patterns. A method for enzymatic assay of the optical purity of iopamidol with lactodehydrogenase is described as well as partition coefficient, ionization constant of the oxyacylamido-group, critical micelle formation, surface tension, and osmolarity.
为了研究高水溶性和低毒性的结构要求，制备了一系列5-羟基酰氨基-2,4,6-三碘-N,N'-羟基-烷基间苯二甲酰胺。在被2-羟乙基、2,3-二羟丙基、1,3-二羟丙基和1,1-二羟甲基-2-氧乙基取代的酰胺中，1,3-二羟丙基取代的酰胺具有最高的水溶性。2,3-二羟丙基部分的旋光拆分以及与两种不同胺形成酰胺均未提高水溶性。S-5-α-羟基丙酰氨基-2,4,6-三碘间苯二甲酸二-(1,3-二羟基-2-丙基酰胺)即碘帕醇具有最佳溶解性。碘帕醇形成无水和一水合物晶体，通过差示热分析、X射线衍射图谱和溶解度图谱进行表征。描述了一种用乳酸脱氢酶酶法测定碘帕醇光学纯度的方法，以及分配系数、氧酰氨基基团的电离常数、临界胶束形成、表面张力和渗透压。
