Abstract
X-ray contrast media (CM) have been used since the first discovery of X-rays by Roentgen in 1895. The function of such media is to opacify an organ or portion of the body to X-rays, providing thereby greater diagnostic information to the physician. Many opaque atoms have been studied in many chemical forms; for example, bismuth, barium, tantalum, strontium, and bromine have all been used in a variety of compounds. Although many water-soluble compounds have been evaluated, by 1980 only two atoms, iodine and bromine, have been found to be of significant diagnostic use. This chapter will devote itself to iodinated organic compounds, since they are by far the most diagnostically useful, in particular, we shall discuss mainly water-soluble compounds. The pertinent literature has been surveyed through mid-1980.
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References
Hoey GB, Wiegert PE, Rands RD Jr (1971) Organic iodine compounds as X-ray contrast media. In: Knoefel PK (ed) Radiocontrast agents, sect 76, vol 1. Pergamon, New York, pp 23–131
Ackerman JH (1970) Diagnostic Agents. In: Burger AA (ed) Medicinal chemistry, 3rd edn. Wiley, New York, pp 1686–1699
Doerge RF, Wilson CO (1977) Diagnostic agents. In: Wilson CO, Gisvold O, Doerge RF (eds) Textbook of organic medicinal and pharmaceutical chemistry. Lippincott, Philadelphia, p 939
Lasser C (1967) Dynamic factors in roentgen diagnosis. Williams and Wilkins, Baltimore
Miller RE, Skucas J (1977) Radiographic contrast agents. University Park Press, Baltimore, pp 329–418, 451–494
Contrast Material Symposium (1980) Invest Radiol [Suppl] 15/6
Wallingford VH (1953) The development of organic iodine compounds as X-ray contrast media. J Am Pharmacol Assoc 42:721–728
See also: Wallingford VH, Becker HH, Kruty M (1952) X-ray contrast media. I. Iodinated acylaminobenzoic acids. J Am Chem Soc 74:4365
Knoefel PA (1971) Binding of iodinated radiocontrast agents to plasma proteins. In: Knoefel PA (ed) Radiocontrast agents, sect 76, vol 1. Pergamon, New York, pp 133–145
Baker CE (1979/1980) Physicians desk reference for radiology and nuclear medicine. Medical Economics, Oradell, p 75
Aspelin P (1979) Effect of ionic and nonionic contrast media on red cell deformability in vitro. Acta Radiol [Diagn] (Stockh) 20:1–12
Guerbet M, Tilly G (1969) 2,4,6-Triiodo-3-(N-hydroxyethyl)carbamoyl)-5-(acetylamino) benzoic acid as an opaquing agent for radiography. French patent 6777, 21 April 1969
Grainger RD (1979) A clinical trial of a new low osmolality contrast medium. Sodium and meglumine ioxaglate (Hexabrix) compared with meglumine iothalamate (Conray) for carotid arteriography. Br J Radiol 52:781–786
Lehninger AL (1975) The molecular basis of cell structure and function. In: Biochemistry, 2nd ed. Worth, New York, p 174
Harrington C, Michie C, Lynch PR, Russel MA, Oppenheimer MJ (1966) Blood brain barrier changes associated with unilateral cerebral angiography. Invest Radiol 1:431–440
Sorensen SE (1971) Changes in vascular permeability after local application of roentgen contrast media in the hamster cheek pouch. Acta Radiol [Diagn] (Stockh) 11:274–288
Waldron RL, Bridgenbraugh RB, Dempsey EW (1974) Effect of angiographic contrast media at the cellular level in the brain: hypertonic vs. chemical action. AJR 122:469–476
Rapoport SI, Hori M, Klatzo I (1972) Testing of hypothesis for osmotic opening of the blood brain barrier. Am J Physiol 223:323–331
Sterrett PR, Bradley IM, Kitten TG, Janssen FH, Holloway SL (1976) Cerebrovascu-lature permeability changes following experimental cerebral angiography. A light and electron microscopic study. J Neurol Sci 30:385–403
Chaplin H, Carlsson E (1961) Change in human red blood cells during in vitro exposure to several roentgenologic contrast media. AJR 86:1127–1137
Giammona ST, Lurie PR, Segar WE (1963) Hypertonicity following selective angiocardiography. Circulation 28:1096–1101
Meyer MW, Read RC (1964) Red cell aggregation from concentrated saline and angiographic media. Radiology 82:630–635
Friesinger GC, Schaffer J, Criley JM, Gartner RA, Ross RJ (1965) Hemodynamic consequences of the injection of radiopaque material. Circulation 31:730–740
Cohen LS, Kokko JP, Williams WH (1969) Hemolysis and hemoglobinuria following angiography. Radiology 92:329–332
Von Bubnoff M, Riecker G (1961) Zellosmolaritat und Zellwassergehalt. Klinische und experimentelle Untersuchungen an Erythrozyten. Klin Wochenschr 39:724–733
Raininko R (1979) Role of hypertonicity in the endothelial injury caused by angiographic contrast media. Acta Radiol [Diagn] (Stockh) 20:410–416
Almen T (1971) Toxicity of radiocontrast agents. In: Knoefel PK (ed) Radiocontrast agents, vol 2. Pergamon, New York, pp 443–550
Fischer HW (1968) Hemodynamic reaction to angiographic media. A survey and commentary. Radiology 91:66–73
Rapoport SI, Thompson HK, Bidinger JM (1974) Equi-osmolal opening of the blood brain barrier in the rabbit by different contrast media. Acta Radiol [Diagn] (Stockh) 15:21–32
Oldendorf WH (1971/1972) Blood brain barrier permeability to lactate. Eur Neurol 6:49–55
Hilal SK, Dauth GW, Hess KH, Gilman S (1978) Development and evaluation of a new water-soluble iodinated myelographic contrast medium with markedly reduced convulsive effects. Radiology 126:417–422
Haughton V, Ho K-C, Unger GF (1977) Arachnoiditis following myelography with water-soluble agents. Radiology 125:731–733
Rapoport SI, Levitan H (1974) Neurotoxicity of X-ray contrast media. AJR 122:186–193
Binz A (1937) History of the uroselectans. Z Urol 31:73–84
Long L Jr, Burger A (1941) Synthesis of some iodinated aromatic compounds. J Am Chem Soc 63:1586–1589
Wang JY-C (1980) Deiodination kinetics of water-soluble radiopaques. J Pharm Sci 69/6:671–675
Fischer H (1978) Contrast media in coronary arteriography: a review. Invest Radiol 13:450–457
Mohl MH, Rizzolo RR, Hoey GB, Gorman AD (1979) Determination of diatrizoic acid in X-ray contrast media by high performance liquid chromatography. 15th Midwest regional meeting, American Chemical Society, St. Louis, 8 November 1979
Hoey GB, Wiegert PE, Rands RD Jr (1971) Organic iodine compounds as X-ray contrast media. In: Knoefel PK (ed) Radiocontrast agents, sect 76, vol 1. Pergamon, New York, p 23
Lasser C (1967) Dynamic factors in roentgen diagnosis. Williams and Wilkins, Baltimore, pp 77–79
Kodama JK, Butler WM, Tusing TW, Hallett FP (1963) Iothalamate: a new intravascular radiopaque medium with unusual pharmacotoxic inertness. Exp Mol Pathol [Suppl] 2:65–80
Melartin E, Tuohimaa PJ, Dabb R (1970) Neurotoxicity of iothalamates and diatrizoates. I. Significance of concentration and cation. Invest Radiol 5:13–21
Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol 12:12–15
Valzelli L (1964) A simple method to inject drugs intracerebrally. Med Exp 11:23–26
Sovak M, Ranganathan R (1980) Stability of nonionic water-soluble contrast media: implications for their design. Invest Radiol 15:S323–S328
Hopkins RM, Tusing TW (1979) Preclinical pharmacology and toxicology evaluation for diagnostic X-ray contrast media. R&D Division, Mallinckrodt, St Louis
Gries H, Pfeiffer H, Speck U, Mützel W (1981) Ionic 5-C-substituted-2,4,6-triio-doisophthalic acid derivatives. German Offen 3,001,293, 16 July 1981
Gries H (1981) 3,5-Dicyano-2,4,6-triiodobenzoic acids. German Offen 3,001,294, 16 July 1981
Priewe H, Rutkowski R, Pirner K, Junkman K (1954) Derivatives of 2,4,6-triiodo-3-aminobenzoic acid. Chem Ber 87:651–658
Hoey GB, Rands RD, Wiegert PE, Chapman DW, Zey RL, DeLaMater GB (1966) X-ray media. II. Synthesis of alkanoylbis(isophthalamic acids) and X-ray contrast agents. J Med Chem 9:964–966
Wiegert PE (1972) 5,5′,5′-(Nitrilotriacetamido)tris-(2,4,6-triiodobenzoic acids). German Offen 2,132,614, 17 Aug 1972
Wiegert PE (1974) (Nitrilotriacyltriimino)tris-(2,4,6-triiodobenzoic acid) compounds for X-ray contrast media. British patent 1,346,795, 13 Feb 1974
Bjork L, Erickson U, Ingelman B (1972) New type of contrast medium in selective coronary arteriography. Ups J Med Sci 77/1:19–21
Bjork L, Erickson UE, Ingelman BGA (1970) New type of contrast medium in arthrography. AJR 109/3:505–510
Bjork L (1959) X-ray contrast agent. French patent M 7251, 8 Sept 1969
Felder E, Pitre D, Fumagalli L, Lorenzotti E (1973) Radiopaque contrast media. XXIV. Synthesis and structure-activity relations of new hexaiodinated radiopaque compounds. Farmaco [Sci] 28/11:912–924
Felder E, Pitre D (1971) 3′,3″-Dicarboxy-2′,2″,4′,4″,6′,6″ hexaiodo-4,7,10,13-tetraoxohexadecane-l,16-dianilide as X-ray contrast agent. German Offen 1,937,211, 4 Feb 1971
Felder E, Pitre D (1969) Nontoxic 4,7,10-trioxatridecanebis(3-carboxy-2,4,6-triiodoanilide) for cholecystography. German Offen 1,922,578, 13 Nov 1969
Pharmacia AB (1970) Hydroxyalkylene bis(acylamino-2,4,6-triiodobenzoic acid) derivatives for use as X-ray visualization agents. British patent 1,207,974, 7 Oct 1970
Pfeiffer H, Speck U, Kolb H (1975) 3,5,9-Trioxaundecane-1, 11-dioxyl-bis(3-carboxyl-2,4,6-triiodoanilide) and its salts. German Offen 2,405,652, 21 Aug 1975
Weinmann HJ, Mützel W, Souchon R, Wegener OH (1981) Experimental water soluble contrast media for computed tomography of the liver. Excerpta Med Int Congr Ser 561:95–100
Bernstein J, Losee KA (1971) Tris(2-(2,4,6-triiodo-3-carboxy-5-acetamido-benzami-do) ethyl) amine. German Offen 2,039,214, 25 Feb 1971
Tilly G, Hardouin MJC, Lautrou J (1977) X-ray contrast media. US patent 4,014,986, 29 March 1977
Tilly G, Hardouin MJC, Lautrou J (1977) X-ray contrast media. US patent 4,065,554, 27 Dec 1977
Thomson KR, Evill CA, Fritzche J, Benness GT (1980) Comparison of iopamidol, ioxaglate and diatrizoate during coronary arteriography in dogs. Invest Radiol 15:234–241
Owman T, Hoevels J (1979) Comparison of monomer, dimer and non-ionized medium at urography with simulated compression. ROEFO 131/3:309–317
Higgins CB, Sovak M, Schmidt WS, Kelley MJ, Newell JD (1980) Direct myocardial effects of intracoronary administration of new contrast material with low osmolality. Invest Radiol 15:39–46
Tilly G, Hardouin JC, Lautrou J (1974) Improvements in or relating to new X-ray contrast media. British patent 1,488,904, 31 May 1974
Tilly G, Hardouin MJG, Lautrou J (1979) New ionic polyiodo benzene derivatives useful as X-ray contrast media. British patent 2,002,583A, 19 Dec 1979
Hebky J, Polacek J (1970) Preparation of 3,5-diaminobenzyl alcohol and its iodinated derivatives. Coll Czech Chem Commun 35/2:667–674
Hebky J, First B, Polacek J, Karasek M (1970) Synthesis of iodinated benzylamine X-ray diagnosis. Coll Czech Chem Commun 35/3:867–881
Hebky J (1970) X-ray contrast agents. Pharm Ind 32/10A:938–940
Hebky J, Polacek J, Tikal I, Lupinek V, Sova M (1976) Synthesis of iodinated derivatives of 3-aminobenzylamine and 3,5-diaminobenzylamine for X-ray diagnosis. Coll Czech Chem Commun 41/10:3094–3105
Van Ootegham SP, Smith RG, Daves G Jr, Chang EM, El-Mazati A, Olsen GD, Riker WK (1976) Iodo-bis(quaternary ammonium) salts. Potential cartilage-selective X-ray contrast agents. J Med Chem 19/11:1349–1352
Sovak M, Weitl FL, Lang JH, Higgins CB (1979) Development of a radiopaque cation: toxicity of the benzylammonium group. Eur J Med Chem Chim Ther 14/3:257–260
Speck U, Klieger E, Mützel W (1981) Triiodinated aminoacetamido isophthalamide X-ray contrast agents. US patent 4,283,381, 11 Aug 1981
Suter H, Zutter H (1975) Diiodofumaric acid derivatives as possible new X-ray contrast agents. Pharm Acta Helv 50/5:151–152
Carnmalm B, Gyllander J, Jonsson HA, Mikiver L (1974) Potential X-ray contrast agents. III. Synthesis of some derivatives of iodomethanesulfonic acid and tris (iodomethyl) acetic acid. Acta Pharm Suec 11/2:161–166
Suter H, Zutter H, Brunner J (1971) Tetraiodoterephthalic acid derivatives as X-ray contrast agents. Helv Chim Acta 54/7:2097–2107
Bedford AJM (1973) Radiographic contrast medium. German Offen 2,136,255, 22 March 1973
Hoey GB (1970) The symposium on contrast media toxicity of the Association of University Radiologists. Invest Radiol 5/6:453
Kleiger E, Schroeder E (1975) Synthesis of N-(3-acylamino-5-alkylcarbamoyl-2,4,6-triiodobenzoyl) amino acids as X-ray contrast agents. Eur J Med Chem Chim Ther 10/1:84–88
Bjork L, Erickson U, Ingelman B (1970) Polymeric contrast media for roentgenologic examination of gastrointestinal tract. Invest Radiol 3:142–148 (and references therein)
Bjork L, Erickson U, Ingelman B, Zaar B (1974) Improved polymeric contrast agents for roentgenologic examination of the gastrointestinal tract. Upsala J Med Sci 79:103–105 (and references therein)
Bjork L, Erickson U, Ingelman B (1976) Preliminary report on angiography with polymeric contrast agents in rabbits and dogs. Ups J Med Sci 81:183–187 (and references therein)
Almen T (1969) Contrast agent design. Some aspects of the synthesis of water soluble contrast agents of low osmolarity. J Theor Biol 24:216–226
Holtermann H (1973) Metrizamide, a nonionic, water soluble contrast medium. Acta Radiol [Suppl] (Stockh) 335:1–4
Kejha J, Radek O, Jelinek V, Nemecek O (1966) X-ray opaque agents. Czech patent 118,444, 15 May 1966 (cf Chem Abstr 66:55207r, 1967)
Kocourek J (1966) A method for the manufacture of 6-O-(2,4,6-triiodophenyl)-D-glucose. Czech patent 120,380, 15 Oct 1966
Almen TO, Haavaldsen J, Nordal N (1971) Nonionic iodinated X-ray contrast media. German Offen 2,031,724, 7 Jan 1971 (cf Chem Abstr 74:99662e, 1971)
Torsten HO, Almen TO, Haavaldsen J, Vegard T (1972) N-(2,4,6-triiodobenzoyl)-sugar amines. US patents 3,701,771, 31 Oct 1972 (and 4,021,481, 3 May 1977)
Suter H, Zutter H, Mueller HR (1971) Iodomethansulfonamides. German Offen 2,201,578, 23 March 1971 (cf Chem Abstr 78:3694a, 1973; see also British patent 1,359,908, 17 July 1974)
Felder E, Pitre D, Tirone P (1977) Radiopaque contrast media. XCIV. Preclinical studies with a new nonionic contrast agent. Farmaco [Sci] 32:835–844
Herskovits TT, Kelly TM (1973) Viscosity studies of aqueous solutions of alcohols, ureas, and amides. J Phys Chem 77:381–388 (and references cited therein)
Rakli FB, Keely MJ (1980) A process for the preparation of a sterile injectable physiologically acceptable solution of an X-ray contrast agent and solutions of the contrast agent and a buffer. British patent 2,031,405, 23 April 1980
Weitl FL, Sovak M, Ohno M (1976) Synthesis of a potential water soluble radiographic contrast medium, 2,4,6-triiodo-3-acetamido-5-N-methylcarboxamidophenyl β-D-glucopyranoside. J Med Chem 10:353–356
Weitl FL, Sovak M, Williams TM, Lang JH (1976) Studies in the design of X-ray contrast agents. Synthesis, hydrophobicity, and solubility of some iodoresorcyl bis β-glucosides. J Med Chem 10:1359–1362
Sovak M (this volume) Introduction
Felder E, Vitale RS, Pitre DF (1977) Water soluble, non-ionizing hydroxy-containing amide derivates of 2,4,6-triiodo-isophthalic acid. US patent 4,001,323, 4 Jan 1977
Felder E, Pitre DE (1976) Easily water-soluble nonionic X-ray contrast agents. German Offen 2,547,789, 24 Jan 1976 (cf Chem Abstr 8s:94103r, 1976)
Pfeiffer H (1979) Method for the preparation of serinol (l,3-dihydroxy-2-amino-propane). German Auslegeschrift 2,742,981, 22 March 1979)
Pfeiffer H, Speck U (1978) New dicarboxylic acid-bis-(3,5-dicarbamoyl-2,4,6-triiodoanilides). German Offen 2,628,517, 5 Jan 1978
Sovak M, Ranganathan R, Speck U (1982) Nonionic dimer: Development and initial testing of intrathecal contrast agents. Radiology 142:115–118
Felder E, Pitre D (1978) Water soluble, nonionic X-ray contrast agent. German Offen 2,805,928, 5 Oct 1978 (cf Chem Abstr 90:127532p, 1979)
Felder E, Vitale RS, Pitre D (1979) Water-soluble, nonionizing, radiopaque compounds and contrast compositions containing the same. US patent 4,139,605, 13 Feb 1979
Tilly G, Hardouin M, Michel JC, Lautrou J (1975) X-ray contrast medium. German Offen 2,456,685, 12 June 1975 (cf Chem Abstr 83:114021b, 1975; see also British patent 1,436,357, 19 May 1976)
Hoey GB, Murphy GP, Wiegert PE, Woods JW (1977) 3,5-Disubstituted-2,4,6-triiodoanilides of monobasic polyhydroxy acids. German Offen 2,643,841, 7 April 1977 (cf Abstr 87:136300, 1977)
Lin Y, Smith KR (1979) N-(2-Hydroxyethyl)-2,4,6-triiodo-3,5-bis-(2-keto-L-gulonamido) benzamide and radiological compositions containing same. 15th American Chemical Society Midwest Meeting, St Louis, 8 Nov 1979
Lin Y (1981) N, N′-Bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-(2-keto-L-gulonamido) isophthalamide and radiological compositions. US patent 4,256,729, 17 March 1981
Tilly G, Hardouin MJC, Lautrou J (1976) X-ray contrast material. German Offen 2,624,153, 23 Dec 1976 (cf Chem Abstr 87:157183, 1977; see also US patent 4,062,934, 13 Dec 1977)
Smith KR (1977) N-Triiodobenzoylaminoacyl derivates of polyhydroxyamines. German Offen 2,710,730, 22 Sept 1977 (cf Chem Abstr 88:2337w, 1978)
Smith KR (1976) L-(3,5-Disubstituted-2,4,6-triiodophenyl)-3-(polyhydroxy-alkyl) urea compounds. German Offen 2,610,500, 25 Nov 1976 (cf Chem Abstr 86:190410e, 1977; see also US patent 4,109,081, 22 Aug 1978)
Smith KR (1976) Polyhydroxyalkyl 3,5-disubstituted-2,4,6-triiodocarbanilate. German Offen 2,541,491, 15 April 1976 (cf Chem Abstr 85:63296, 1976; see also US patent 4,125,706, 14 Nov 1978)
United States Pharmacopoeia, 20th revision. US Pharmacopoeial Convention, Rockville, p 1037 (and references therein)
Ackerman JH, Laidlaw GM, Snyder CA (1969) Restricted rotational isomers I. Hindered triiodoisophthalic acid derivatives. Tetrahedron Lett 44:3879
Ackerman JH, Laidlaw GM (1969) Restricted rotational isomers II. Maleimido derivatives of the cis and trans isomers of 5-amino, 2,4,6-triiodo-N,N,N′,N′-tetra-methylisophthalimides. Tetrahedron Lett 51:4487
Ackerman JH, Laidlaw GM (1970) Restricted rotational isomers III. Cis and trans 3′,5′-(dimethylcarbamoyl)-2′,4′,6′-triiodooxalanilic acid and their N-methyl derivatives. Tetrahedron Lett 27:2381
Hol L, Kelly M, Salvesen S (1977) Metrizamide. In: Goldberg ME (ed) Pharmacological and biochemical properties of drug substances. American Pharmacological Association, Washington (Academy pharmacological sciences, vol 1, pp 387–412)
McCall JM (1975) Liquid-liquid partition coefficients by high pressure liquid chromatography. J Med Chem 18:549–552
Rizzolo RR, Smith KR, Hoey GB, Reed RD, Ehrhard EJ (1979) Relationship between toxicity and HPLC retention times of nonionic iodinated X-ray contrast media. 15th American Chemical Society Midwest Meeting, St Louis, 8 Nov 1979
Larmaque JL, Bruel JM, Dondelinger B, Vendrell B, Pelissier O, Rouanet JP, Michel JL, Boulet P (1979) The use of iodolipids in hepatosplenic computed tomography. J Comput Assist Tomogr 3/1:21–24
Vermess M, Chatterji BC, Doppman JL, Grimes G, Adamson RH (1979) Development and experimental evaluation of a contrast medium for computed tomographic examination of liver and spleen. J Comput Assist Tomogr 3:25–31
Vermess M, Adamson RH, Doppman JL, Rapson AS, Herdt JR (1976) Intravenous hepatospleenography. Experimental evaluation of a new contrast material. Radiology 119/1:31–37
Grimes G, Vermess M, Galielli JF, Girton M, Chatterji BD (1979) Formulation and evaluation of ethiodized oily emulsion for intravenous hepatography. J Pharm Sci 68/1:52–56
Roth SL, Dumbrowski H, Heiort U, Kalbfleisch H, Ludwig J, Siefart F, Saeher A, Vielhauer E (1979) A new contrast medium emulsion for lymphography. ROFO 131/3:317–321
Villemein T, Morre J, Laval-Jeantet AM, Laval Jeantet M (1973) Experimental hepatography in the rat by selective intraarterial injection of an iodolipid emulsion. Ann Radiol (Paris) 16/7–8:527–532
Arbadus BT, Ferno OB, Linderot TO (1971) X-ray contrast agent. German patent 1,617,275, 13 May 1971
Roth S (1977) X-ray contrast agent based on an emulsion of iodinated oils. German patent 2,602,907, 28 July 1977
Fritsch G, Voigt R, Lleuning M (1970) Preparation of a contrasting emulsion agent for lymphography. Pharmazie 25/4:248–252
Newton BN (1976) Iodine containing organic carbonates as investigative radiopaque compounds. J Med Chem 19/12:1362–1366
Newton BN (1977) Iodine containing organic carbonates for use as radiographic agents. US patent 4,022,814, 10 May 1977
Newton BN (1978) Structure-toxicity relationships of iodinated organic carbonates and related compounds. J Pharm Sci 67/8:1154–1157
Newton BN (1978) Iodinated thiolcarbonates for use as radiographic contrast agents. US patent 4,125,554, 14 Nov 1978
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Larsen AA (1964) Iodinated esters of substituted benzoic acids and preparations thereof. US patent 3,119,858, 20 Aug 1964
Felder E, Pitre D, Tirone P, Zingales AH (1978) Radiopaque contrast media. XLV. Experimental lymphography with crystal suspensions. Farmaco [Sci] 33/4:302–314
Felder E, Pitre E (1976) New X-ray media and methods for their preparation. German Offen 2,625,826, 23 Dec 1976
Felder E, Vitale RS, Pitre D (1977) Radiopaque esters of tetriiodoteraphthalic acid. US patent 4,044,048, 23 Aug 1977
Kaude JE, Abrams RM, Daly JW (1978) Percutaneous indirect lymphography with a new experimental contrast medium — a preliminary report. Angiology 29/2:162–168
Zutter H, Brunner J (1970) New X-ray contrast media, their use and methods for their preparation. German Offen 1,958,333, 27 Aug 1970
Schic M, Povse T, Zupet T (1971) Bronchography using an iodine contrast agent substituted at the ester of 3,5-diiodo-4-pyridone in N-carboxylic acid ester. Tekhnika 26/4:158–159
Povse T, Zupet T, Japelj N (1971) Tekhnika 26/4:333–336
French Patent 2,180,568 (1974) Contrast material for radiologic examinations, 4 Jan 1974
Soulal MJ, Utting K (1974) Acetoxymethyl and peivaloyloxymethyl 5-acetamido-2,4,6-triiodo-N-methylisophthalamates. US patent 3,795,698, 3 May 1974
Soulal MJ, Utting K (1975) Derivatives of 3-acetamido-2,4,6-triiodobenzoic acid. German Offen 2,428,140, 23 Jan 1975
Hoey GB (1980) Lower alkoxymethyl esters of 2,4,6-triiodobenzoic acid derivatives. US patent 4,225,725, 30 Sept 1980
Long EM, Liu MS, Dobben GB, Scanto PF, Aranbulo AS (1976) Radiopaque applications of brominated fluorocarbon compounds in experimental animals and human subjects. Am Chem Soc Ser 28:171–189
Enzmann D, Young SY (1979) Applications of perfluorinated compounds as contrast agents in computed tomography. J Comput Assist Tomogr 3/5:622–626
Brahme F, Sovak M, Powell H, Long DM (1975) Perfluorocarbon bromides as contrast media in radiography of the central nervous system. Acta Radiol [Suppl] (Stockh) 347
Felder E, Tanara CB (1976) Radiopaque contrast media. XXXIII. Oral cholecystography, a review. Farmaco [Sci] 31:283–294
Stagner WC, Guillory JK (1979) Physical characterization of solid iopanoic acid forms. J Pharm Sci 68:1005–1009
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Pitre D, Felder E (1976) Radiopaque contrast media. XLII. Metabolism of iopronic acid in human. Farmaco [Sci] 31:540–546
Pitre D (1976) Radiopaque contrast media. XL. Isolation and identification of the metabolites of iopronic acid in the urine and bile of the dog. Farmaco [Sci] 31:516–528
Pitre D, Fumagalli L (1976) Radiopaque contrast media. XLI. Isolation and identification of the metabolites of iopronic acid in the rat. Farmaco [Sci] 31:529–539
Raffaeli E, Facino RM, Salmona M, Pitre D (1977) In vitro binding and metabolism of iopronic acid by rat liver microsomes. Pharmacol Res Commun 9:833–846
Pitre D, Facino RF (1976) Radiopaque contrast media. XXXIX. Metabolism of iopronic acid by rat liver microsomes: characterization and identification of the metabolites. Farmaco [Sci] 31:755–762
Felder E, Pitre D (1972) 3[ω[3-(Acylamino)-2,4,6-triiodophenoxy]alkoxy]-2-alkyl-propinoic acids. German Offen 2,128,902. 22 June 1972
Felder E, Pitre D, Fumagalli L, Lorenzotti E (1976) Radiopaque contrast media. XXXIV. Derivatives of ω-(3-amino-2,4,6-triiodophenoxy)alkoxyalkanoic acids. Farmaco [Sci] 31:349–363
Felder E, Pitre D, Frandi M (1976) Radiopaque contrast media. XXXV. Physical properties of iopronic acid, a new oral cholecystographic agent. Farmaco [Sci] 31:426–437
Felder E, Zingales MF, Tiepolo U (1976) Radiopaque contrast media. XXXVI. Iopronic acid: proposed analytical monograph. Farmaco [Prat] 31:383–396
Pitre D, Frigerio A, Maffei-Facino R (1976) Identification of some urinary metabolites of iopronic acid in human, rat and dog. Mass spectrum drug metab, Proc int symp, pp 13–30
Tirone P, Rosati G (1976) Radiopaque contrast media. XXXVII. Iopronic acid, a new contrast medium for oral chelecystography: pharmacologic investigation. Farmaco [Prat] 31:397–412
Tirone P, Rosati G (1976) Radiopaque contrast media. XXXVIII. Iopronic acid, a new contrast medium for oral cholecystography: toxicologic investigation. Farmaco [Prat] 31:437–446
Lewis TR, Archer S (1949) Preparation of some iodinated aminophenylalkanoic acids. J Am Chem Soc 71:3753–3755
Priewe H, Poljak A (1960) Foramidino derivatives of β-(2,4,6-triiodo-3-aminophenyl) alkanoic acids. Chem Ber 93:2347–2352
Obendorf W (1962) 3-Amino-2,4,6-triiodoaminobenzoyl compounds for use as X-ray contrast agents. German patent 1,085,048. Appl 6 Aug 1958 (ch Chem Abstr 56:5884h, 1962). US patent 3,051,745, 28 Aug 1962
Archer S, Hoppe JO (1959) Acylated triiodoaminophenylalkanoic acids. US patent 2,895,988, 21 July 1959
Almen T (1971) 2,4,6-Triiodobenzoic acid derivaties: methods for their preparation and properties as X-ray contrast media. In: Knoefel P (ed) Radiocontrast agents, vol 2. Pergamon, New York, p 688
Salvesen S, Haugen LG, Haavaldsen J, Nordal V (1971) Triiodobenzoic acid derivatives as X-ray contrast agents. Norwegian patent 122430, 28 June 1971
See also: Haugen LG, Salvesen S, Haavaldsen J, Nordal V (1969) Substituted 2,4,6-triiodobenzoic acids, X-ray contrast media. German Offen 1,928,838, 11 Dec 1969
Felder E, Pitre D, Grandi M (1977) Radiopaque contrast media. XLIII. Physico-chemical properties of iodamide. Farmaco [Sci] 32/10:755–766
Bernstein J, Losee KA (1972) 2,4,6-Triiodobenzoic acid derivatives. Methods for their preparation and properties as X-ray contrast media. German Offen 2,129,936, 27 Jan 1972
Wiegert PE (1976) 2,4,6-Triiodo-5-methoxyacetamido-N-methylisophthalamic acid compounds and their use in X-ray contrast media. German Offen 2,528,795, 12 Feb 1976
Tilly G (1971) Opaquing agents for radiography. French demande 2,074,734, 12 Nov 1971
Tilly G (1971) Iodinated radiocontrast agents. German Offen 211,750, 28 Oct 1971 (and French demande 2,085,636, 4 Feb 1972: Iodinated radiocontrast agents; also Norwegian patent 122430, 28 June 1971)
Haugen LG, Salvesen S, Haavaldsen J, Nordal V (1969) Substituted 2,4,6-triiodoben-zoic acids, X-ray contrast media. German Offen 1,928,838, 11 Dec 1969
Pfeiffer H, Zoellner G, Beich W (1972) 3-Acetamido-5-(hydroxyacetamido)-2,4,6-triiodobenzoic acid-containing contrast media. German Offen 211,829, 26 Oct 1972 (and references therein)
Wiegert PE (1978) 2,4,6-Triiodobenzoic acid derivatives. Methods of preparation and use as X-ray contrast media. German Offen 2,732,825, 23 Feb 1978
Sterling Drug Co. (1970) Iodonated imido-benzoic acids. British patent 1,191,015, 5 May 1970
Ackerman JH (1969) Triiodoaniline derivatives. German Offen 1,915,196, 20 Nov 1969
Zupet P, Povse T, Japelj M, Sehic M, Obrez I, Bulic D (KRKA Inst. Raziskave Raz-vo) (1975) Novo Mesto, Yugoslavia. Kern Ind 24/7:379–381
Wiegert PE (1976) Substituted 2,4,6-triiodoisopnthalamic acids for use in X-ray contrast media. German Offen 2,526,848, 2 Jan 1976
Kleiger E, Speck U (1978) Iodinated isophthalamic acid derivatives. German Offen 2,629,228, 5 Jan 1978 (see also Belgian patent 856,095, 27 Dec 1977)
Schering AG (1977) Iodinated isophthalamic acid derivatives. Belgian patent 856,095, 27 Dec 1977
Dagra NV (1971) X-Ray contrast medium containing a shielding component. Netherlands Appl 6,912,102, 10 Feb 1971 (CA 75:35436 (19), 1971)
Kneller MT (1978) Oxazolinylacetamidotriiodobenzoic acid X-ray contrast agents., US patent 4,066,743, 3 Jan 1978
Tilly G (1972) Triiodobenzene derivatives as X-ray contrast media. German Offen 2,216,627, 19 Oct 1972
Klieger E, Schroeder E (1973) Synthesis of N-(carbamoylalkyl)triiodoisophthalamic acids and their use as X-ray contrast media. Arch Pharm (Weinheim) 306/11:834–845
Klieger E, Beich W, Schroeder E (1976) Triiodoisophthalamic acid monoamino acid amides. US patent 3,953,501, 27 April 1976
Klieger E, Beich W, Schroeder E (1973) N-3-Carbamoyl(or carboxy)-5-acetamido-2,4,6-triiodobenzoyl amino acids (or amides) for X-ray contrast media. German Offen 2,207,950, 23 Aug 1973
Bernstein J, Losee KA (1972) Substituted triiodoisophthalamic acids. US patent 3,666,800, 30 May 1972
Ackerman JH (1970) Iodinated imido-benzoic acids. British patent 1,191,015, 6 May 1970
Felder E, Pitre D, Zutter H (1974) 5-(Acetamidomethyl)-3-acetyl(2,3-dihydroxypropyl) amino-2,4,6-triiodobenzoic acid. German Offen 2,229,360, 7 Nov 1974 (see also French demande 2,150,805, 26 Aug 1971; US patent 3,360,436, 26 Dec 1967)
Felder E, Pitre D (1975) 3-Hydroxyacylaminomethyl-5-acylamino-2,4,6-triiodobenzoic acids and their use as X-ray contrast materials. German Offen 2,425,912, 20 March 1975
Felder E, Pitre D (1975) X-ray contrast medium. German Offen 2,422,718, 13 Feb 1975
Klieger E (1972) Synthesis of triiodo-phenylacetic acid derivatives and their use as X-ray contrast agents. Chim Ther 7/6:475–478
Pfeiffer H, Zoellner G, Geich W (1972) Circulation-compatible 5-hydroxy (and alkoxy) acetamido-3-(acetamidomethyl)-2,4,6-triiodobenzoic acids for X-ray contrast media. German Offen 2,124,904, 7 Dec 1972
Klieger E, Schroeder E (1976) Preparation of new hexaiodated X-ray contrast materials. Eur J Med Chem Chim Ther 11/3:283–286
Klieger E, Speck U, Schroeder E (1976) Dicarboxylic acid derivatives of triiodoisoph-thalic acid monoamino acid amides and their use as X-ray contrast media. German Offen 2,505,320, 5 Aug 1976
Ekstrand TKIV, Ronlan A, Wickberg BV, Munksgaard AH (1973) X-ray contrast agent. German Offen 2,038,263, 22 Feb 1973
Bernstein J, Loese KA (1971) N,N′-Trimethylenebis(5-(3-methylureido)-2,4,6-triiodoisophthalamic acid as X-ray contrast medium. German Offen 2,038,263, 18 Feb 1971
Bernstein J, Losee KA (1971) N,N′-Bis 5-(3-methylureido)-3-carboxy-2,4,6-triiodophenyl adipamide. German Offen 2,130,369, 23 Dec 1971
Ekstrand TKI, Munksgaard A, Ronlan A, Wickberg BV (1971) N,N′-Bis(triiodophenyl) alkylenediamines as X-ray contrast media. German Offen 2,111,127, 21 Oct 1971
Bjork L, Erickson UE, Ingelman BGA (1973) Derivative of 3,5-dialkanoylamino-2,4,6-triiodobenzoic acid and its use as X-ray contrast medium. Swedish patent 354,853, 26 March 1973
Tilly G (1975) N,N′-Dimethyliocarmic acid derivatives useful as radiography opacifies. British patent 1,385,684, 26 Feb 1975
Ingelman BGA (1969) Radiopaque iodocompounds. German Offen 1,816,844, 24 July 1969
Klieger E, Speck U, Schroeder E (1977) Triiodoisophthalamic acids, useful as X-ray contrast agents. German Offen 2,554,148, 6 Aug 1977 (see also Belgian patent 856,095, 23 Dec 1977)
Gries H, Pfeiffer H (1977) Triiodized N-methyldicarboxylic acid anilides. US patent 4,001,298, 4 Jan 1977
Gries H, Pfeiffer H (1977) Dicarbopylic acid derivatives of triiodoisophthalic acid mono-amides. Methods for their preparation and their use as X-ray contrast media. German Offen 2,554,148, 6 Aug 1977
Felder E, Pitre D (1969) Alkanedioylbis(3-acylaminomethyl-5-carboxy-2,4,6-triiodoanilides). German Offen 1,922,606, 13 Nov 1969
Felder E, Pitre D (1969) New X-ray contrast media. German Offen 1,922,613, 2 May 1969
Gries H (1972) 3-(Methylamino)-2,4,6-triiodophenyl derivatives. German Offen 2,050,217, 6 April 1972
Felder E, Pitre D (1974) 3-(Acylamino)-5-(alpha-hydroxyalkyl)-2,4,6-triiodobenzoic acids as X-ray contrast media. German Offen 2,317,535, 30 May 1974
Bernstein J, Sowinski FA (1975) 3,5-Disubstituted-2,4,6-triiodobenzoic acids. US patent 3,914,294, 21 Oct 1975
Tilly G, Hardouin MJC, Lautrou J (1975) X-ray contrast media. German Offen 2,523,567, 11 Dec 1975
Klieger E, Schroeder E (1975) Synthesis of N-(3-acylamino-5-alkylcarbamoyl-2,4,6-triiodobenzoyl)amino acids as X-ray contrast agents. Eur J Med Chem Chim Ther 10/1:84–88
Murphy GP, Hoey GB, Wiegert PE, Smith KR, Lin Y, El-Antably SM, Friedman MD, Kneller MT, Reed RD, Hopkins RM, VanDeripe DR, Adams MD, Lau DHM, Valenti A (1979) Synthesis and toxicological evaluation of nonionic iodinated X-ray contrast media. 15th Midwest American Chemical Society Meeting, St Louis, 8 Nov 1979
Sovak M, Nahlovsky B, Lang J, Lasser ES (1975) Preliminary evaluation of di-iodotriglucosyl benzene. An approach to the design of nonionic water-soluble radiographic contrast media. Radiology 117:717–719
Sovak M, Johnson M, Ranganathan R (1979) Improved screening of acute toxicity of novel contrast media. Invest Radiol 14:378
Sovak M, Ranganathan R (1980) Stability of nonionic water-soluble contrast media. Invest Radiol [Suppl], p 3327
Nordal V, Holterman H (1977) Iodine-containing isophthalamide derivates. German Offen 2,727,196, 22 Dec 1977 (cf Chem Abstr 88:152269z, 1978; see also US patent 4,250,113, 10 Feb 1981)
Tilly G (1968) 4-[2,4,6-Triiodo-3-morpholino carbonyl)phenoxy]-butyric acid. French CAM 202, 24 June 1968 (cf Chem Abstr 72:43699p, 1970)
Speck U, Blasskiewicz P, Seidelmann D, Kleiger E (1980) New nonionic X-ray contrast media. German Offen 2,909,439, 19 Sept 1980
Gries H, Pfeiffer H, Speck U, Mützel W (1981) Nonionic 5-C-substituted 2,4,6-triiodoisophthalic acid derivates. German Offen 3,001,292, 16 July 1981
Felder E, Pitre D (1972) 2-Alkyl-3-[2-(3-carbamoyl-2,4,6-triiodophenoxylethoxy] propionic acids as X-ray contrast media. German Offen 2,212,741, 28 Dec 1972 (cf Chem Abst 78:71710c, 1973)
Bernstein J, Sowinski FA (1972) 3-[4-(3-Hydroxy-2,4,6-triiodophenoxy)phennylalanine. French demande 2,182,161, 27 April 1972 (cf Chem Abstr 80:133827y, 1974)
Felder E, Pitre D (1969) Aminotriiodophenylpropionic acids as contrast agents. Swiss patent 480,071, 15 Dec 1969 (cf Chem Abstr 72:100292b, 1970)
Pfeiffer H, Kolb KH, Harwart A, Schulze PE (1971) 3-(2,4,6-Triiodo-3-amidino-phenyl) propionic acids as X-ray contrast media. German Offen 1,956,844, 19 May 1971 (cf Chem Abstr 75:35474b, 1971)
Ackerman JH (1972) 3-(Carboxyalkanoylamino)-2,4,6-triiodohydrocinnamic acids. US patent 3,637,825, 25 Jan 1972
Ackerman JH (1968) 3-Cyclic imides of 3-amino-2,4,6-triiodohydrocinnamic acids. US patent 3,655,669, 25 March 1968
Ackerman JH (1977) 3-Acylamino-2,4,6-triiodobenzoic acids. US patent 4,031,088, 21 June 1977
Felder E, Pitre D, Fumagalli L, Lorenzotte E (1970) Radiopaque contrast media. XVIII. Derivatives of 2-(3-amino-2,4,6-triiodophenyl)alkanoic acids. J Med Chem 13:559–561
Pitre D, Fumagalli L, Lorenzotti E (1972) Radiological contrast media. XXI. Iodo derivatives of aryl [3-(N-alkylacylamino)phenoxy]acetic acid. Formaco [Sci] 27:408–418
Skulan TW (1977) Diagnostic process using sodium tyropanoate. US patent 4,002,711, 11 Jan 1977
Hoppe JO, Ackerman JH, Larsen AA (1970) Sodium tyropanoate, a new oral cholecystographic agent. J Med Chem 13:997–999
Holtermann H (1969) N-(Hydroxyalkyl)-2′,4′,6′-triiodosuccinanilic acids, cholecystographic contrast media. German Offen 1,927,557, 18 Dec 1969 (cf Chem Abstr 72:66587q, 1970)
Cassebaum H, Dierbach K (1969) Alkyl substituted-N-(2,4,6-triiodo-3-aminophenyl)-glutaramidic acids. German (East) patent 67,209, 5 June 1969 (cf Chem Abstr 72:66654j, 1970)
Cassebaum H, Dierback K, Bekker H (1972) Iodinated N-aryldicarboxylic acid monoamides as orally applied bile contrast media. Pharmazie 27:391–395
Obendorf W, Lindner I (1969) 3-Amino-2,4,6-triiodobenzamide derivatives as X-ray contrast agents. Austrain patent 275,025, 10 Oct 1969 (cf Chem Abstr 72:78726x, 1970)
Clauss W, Speck U, Jentsch D (1976) Oral X-ray contrast medium. German Offen 2,505,218, 19 Aug 1976 (cf Chem Abstr 85:166652u, 1976)
Korver JA (1977) Radiographic contrast agents containing N-acetyl-N-(3,5-diamino-2,4,6-triiodophenyl)aminopropionic acid derivatives. French demande 2,313,917, 7 Jan 1977 (cf Chem Abstr 88:16159m, 1978)
Dagra NV (1979) Triiodophenylaminopropionic acids and their use in X-ray contrast media. Belgian patent 874,988, 16 July 1979 (cf Chem Abstr 91:175027v, 1979)
Suter H, Pitre D, Fumagalli L (1969) Amino-triiodobenzamidophenylalkanoic acids as contrast media. Swiss patent 480,070, 15 Dec 1969 (cf Chem Abstr 72:100300c, 1970)
Suter H, Pitre D, Fumagalli L (1970) Roentgen contrast media containing [(3-amino-2,4,6-triiodobenzoyl)aminophenyl]alkanoic acid as shadow imaging component. Swiss patent 490,090, 30 June 1970 (cf Chem Abstr 73:112947c, 1970)
Obendorf W, Lindner I, Schwarzinger E, Krieger J (1974) Cyclic amidines for X-ray contrast medium. German Offen 2,235,915, 7 Feb 1974 (cf Chem Abstr 80:108538p, 1974)
Obendorf W, Lindner I, Schwarzinger E, Krieger J (1974) [(Aminoalkylidene)-amino]triiodobenzamide derivatives for X-ray contrast media. German Offen 2,235,935, 7 Feb 1974 (cf Chem Abstr 80:108545x, 1974)
Obendorf W, Schwarzinger E, Krieger J, Lindner I (1974) X-ray contrast medium. Austrian patent 319,463, 27 Dec 1974 (cf Chem Abstr 82:160245e, 1975)
Obendorf W, Schwarzinger E, Krieger J, Lindner I (1974) Iodine-substituted cyclic amidines as X-ray contrast agents. Austrian patent 319,226, 10 Dec 1974 (cf Chem Abstr 83:9777e, 1975)
Obendorf W, Schwarzinger E, Krieger J, Lindner I (1975) X-ray contrast material. Austrian patent 320,139, 27 Jan 1975 (cf Chem Abstr 83:654998b, 1975)
Obendorf W, Lindner I, Schwarzinger E (1978) N-Acyl derivatives of 3-amino-2,4,6-triiodobenzoic acid. German Offen 2,732,599, 20 April 1978 (cf Chem Abstr 89:42838x, 1978)
Obendorf W, Schwarzinger E (1979) N-Acyl derivatives of 3-amino-2,4,6-triiodobenzoic acid. US patent 4,152,526, 1 May 1979
Ackerman JH (Sterling Drug Inc.) (1969) 3,3′-[Alkylenebis(carbonylimino)]bis[2,4,6-triiodobenzoic acids]. British patent 1,164,526, 17 Sept 1969 (cf Chem Abstr 71:123989c, 1969; see also US patent 3,542,861 and/or German Offen 1,618,001)
Rosenberg FJ, Ackerman JH, Nickel AR (1980) Iosulamide: A new intravenous cholangiocholecystographic medium. Invest Radiol [Suppl] S142
Sovak M, Ranganathan R, Douglass I, Gallagher I, Nagavajan G (1983) New concepts in CM synthesis: development of a new nonionic contrast medium. Invest Rad (Suppl) 19
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Hoey, G.B., Smith, K.R. (1984). Chemistry of X-Ray Contrast Media. In: Sovak, M. (eds) Radiocontrast Agents. Handbook of Experimental Pharmacology, vol 73. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69515-5_2
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