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【结 构 式】 
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【药物名称】Technetim (99mTc) tiatide, Technetium (99mTc) mertiatide, MAG3-[99mTc], [99mTc]-MAG3, MAGscinti, Technescan MAG3 【化学名称】99mTc-Mercaptoacetylglycylglycylglycine disodium salt 【CA登记号】125224-05-7, 104348-91-6 (anion), 104758-54-5 (free acid), 66516-09-4 (ligand), 104318-29-8 (unlabeled;free acid) 【 分 子 式 】C8H8N3Na2O6STc 【 分 子 量 】419.21306 |
【开发单位】Mallinckrodt (Originator), Nihon Medi-Physics (Originator), Daiichi Radioisotope (Licensee), Nippon Isotope Assoc. (Licensee) 【药理作用】DIAGNOSTIC AGENTS, Radiopharmaceuticals, Radiopharmaceuticals for Renal Function, Technetium Complexes |
合成路线1
The benzoyl-protected ligand (IV) was prepared as follows. Acylation of triglycine (I) with chloroacetyl chloride (II) produced the chloroacetamide (III). Subsequent treatment of chloride (III) with sodium thiobenzoate yielded thioester (IV). The title 99technetium complex was prepared by in situ hydrolysis of the thiobenzoate ester (IV) to mercaptoacetyl triglycine (V) in the presence of a solution of [99mTc]pertechnetate, SnCl2 as the technetium reducing species, and gluconate or tartrate as intermediate Tc complexing agents.
| 【1】 Hung, J.C.; et al.; Rapid preparation and quality control of technetium-99m MAG3(TM). J Nucl Med Technol 1991, 19, 3, 176. |
| 【2】 Reyes-Herrera, L.; et al.; An alkaline kit formulation to obtain [99mTc]MAG3 in high radiochemical yields. J Radioanal Nucl Chem 1995, 199, 6, 507. |
| 【3】 Grummon, G.; et al.; Synthesis, characterization and crystal structures of technetium(V)-oxo complexes useful in nuclear medicine. 1. Complexes of mercaptoacetylglycylglycylglycine (MAG3) and its methyl ester derivative (MAG3OMe). Inorg Chem 1995, 34, 7, 1764. |
| 【4】 Fritzburg, A. (University of Utah); Radiolabeled technetium chelates for use in renal function determinations. EP 0173424 . |
| 【5】 Fritzberg, A.R.; Kasina, S.; Eshima, D.; Johnson, D.L.; Synthesis and biological evaluation of technetium-99m MAG3 as a hippuran replacement. J Nucl Med 1986, 27, 1, 111. |
| 【6】 Brandau, W.; et al.; Technetium-99m labeled renal function and imaging agents. 3. Synthesis of Tc-99m-MAG3 and biodistribution of by-products. Int J Radiat Appl Instrum Part A - Appl Radiat Isotop 1988, 39, 2, 121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 56518 | 2-({2-[(2-aminoacetyl)amino]acetyl}amino)acetic acid | C6H11N3O4 | 详情 | 详情 | |
| (II) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (III) | 56519 | 2-{[2-({2-[(2-chloroacetyl)amino]acetyl}amino)acetyl]amino}acetic acid | C8H12ClN3O5 | 详情 | 详情 | |
| (IV) | 56520 | 1,4,7,10-tetraoxo-1-phenyl-2-thia-5,8,11-triazatridecan-13-oic acid | C15H17N3O6S | 详情 | 详情 | |
| (V) | 56521 | 2-{[2-({2-[(2-sulfanylacetyl)amino]acetyl}amino)acetyl]amino}acetic acid | C8H13N3O5S | 详情 | 详情 |
合成路线2
The protected ligand (IV) was also prepared by a related method. The acylation of thioglycolic acid (V) with benzoyl chloride (VI) under Schotten-Baumann conditions afforded S-benzoyl thioglycolic acid (VII). After activation of (VII) as the corresponding succinimidyl ester (VIII) with N-hydroxysuccinimide and DCC, coupling with triglycine (I) furnished compound (IV).
| 【1】 Grummon, G.; et al.; Synthesis, characterization and crystal structures of technetium(V)-oxo complexes useful in nuclear medicine. 1. Complexes of mercaptoacetylglycylglycylglycine (MAG3) and its methyl ester derivative (MAG3OMe). Inorg Chem 1995, 34, 7, 1764. |
| 【2】 Brandau, W.; et al.; Technetium-99m labeled renal function and imaging agents. 3. Synthesis of Tc-99m-MAG3 and biodistribution of by-products. Int J Radiat Appl Instrum Part A - Appl Radiat Isotop 1988, 39, 2, 121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 56518 | 2-({2-[(2-aminoacetyl)amino]acetyl}amino)acetic acid | C6H11N3O4 | 详情 | 详情 | |
| (IV) | 56520 | 1,4,7,10-tetraoxo-1-phenyl-2-thia-5,8,11-triazatridecan-13-oic acid | C15H17N3O6S | 详情 | 详情 | |
| (V) | 18524 | 2-sulfanylacetic acid | 68-11-1 | C2H4O2S | 详情 | 详情 |
| (VI) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (VII) | 56522 | 2-(benzoylsulfanyl)acetic acid | C9H8O3S | 详情 | 详情 | |
| (VIII) | 56523 | S-{2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-2-oxoethyl} benzenecarbothioate | C13H11NO5S | 详情 | 详情 |
合成路线3
Other S-protecting groups for mercaptoacetyl triglycine have been reported. The S-benzyl derivative (X) was prepared by condensation of triglycine (I) with (benzylthio)acetyl chloride (IX). Alternatively, the S-benzamidomethyl compound (XII) was prepared as follows. Thioglycolic acid (V) was condensed with benzamidomethanol under acidic conditions to give S-(benzamidomethyl)thioglycolic acid (XI), which was then coupled to triglycine (I) using DCC/HOBt. Deprotection in the presence of 99Tc pertechnetate under the same conditions as above furnished the title Tc complex.
| 【1】 Okarvi, S.M.; et al.; Comparison of the labelling characteristics of mercaptoacetyltriglycine (MAG3) with different S-protective groups. J Label Compd Radiopharm 1997, 39, 10, 853. |
| 【2】 Bormans, G.; et al.; Investigation of the labelling characteristics of 99mTc-mercaptoacetyltriglycine. Nucl Med Biol 1995, 22, 3, 339. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 56518 | 2-({2-[(2-aminoacetyl)amino]acetyl}amino)acetic acid | C6H11N3O4 | 详情 | 详情 | |
| (V) | 18524 | 2-sulfanylacetic acid | 68-11-1 | C2H4O2S | 详情 | 详情 |
| (IX) | 56524 | 2-(benzylsulfanyl)acetyl chloride | C9H9ClOS | 详情 | 详情 | |
| (X) | 56525 | 4,7,10-trioxo-1-phenyl-2-thia-5,8,11-triazatridecan-13-oic acid | C15H19N3O5S | 详情 | 详情 | |
| (XI) | 56526 | 2-{[(benzoylamino)methyl]sulfanyl}acetic acid | C10H11NO3S | 详情 | 详情 | |
| (XII) | 56527 | 1,6,9,12-tetraoxo-1-phenyl-4-thia-2,7,10,13-tetraazapentadecan-15-oic acid | C16H20N4O6S | 详情 | 详情 |