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【结 构 式】 
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【药物名称】Indium In 111 pentetreotide, 111In-Pentetreotide, 111In-DTPA-octreotide, MP-1727, DTPA-SMS(noncomplexed), SDZ-215811s(noncomplexed), SDZ-215-811(noncomplexed), Somatother, OctreoScan 【化学名称】Hydrogen [N-[2-[[2-[bis(carboxymethyl)amino]ethyl](carboxymethyl)amino]ethyl]-N-(carboxymethyl)glycyl-D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N1-[2(R)-hydroxy-1(R)-(hydroxymethyl)propyl]-L-cysteinamide cyclic (3--8)-disulfidato(4-)]indate(1-)-111In 【CA登记号】139096-04-1, 138661-02-6 (non-complexed) 【 分 子 式 】C63H84InN13O19S2 【 分 子 量 】1506.39563 |
【开发单位】Mallinckrodt (Originator), Novartis (Originator), Altana Pharma (Licensee) 【药理作用】Diagnostic Agents, Diagnostic for Cancer, Somatostatin Analogs |
合成路线1
The selective protection of D-Phe1-octreotide peptide (I) with Boc2O gives the monoprotected peptide (II), which is condensed with diethylenetriaminopentaacetic acid (DTPA) dianhydride (III) by means of NaHCO3 in dioxane/water to yield the adduct (IV). The treatment of (IV) with TFA affords the desired DTPA-octreotide derivative (V), which is finally labeled with 111InCl3 in acetic acid or in ammonium citrate to afford the target indium derivative. The starting D-Phe1-octreotide peptide (I) has been obtained by the conventional methods of peptide synthesis using a peptide synthesizer.
| 【1】 Wu, Y.-T.; et al.; Direct solid phase synthesis of biologically active peptide alcohols. J Chin Chem Soc (Taipei) 1999, 46, 2, 135. |
| 【2】 Edwards, W.B.; et al.; Generally applicable, convenient solid-phase synthesis and receptor affinities of octreotide analogs. J Med Chem 1994, 37, 22, 3749. |
| 【3】 Hsieh, H.-P.; et al.; Direct solid-phase synthesis of octreotide conjugates: Precursors for use as tumor-targeted radiopharmaceuticals. Bioorg Med Chem 1999, 7, 9, 1797. |
| 【4】 Arano, Y.; et al.; Conventional and high-yield synthesis of DTPA-conjugated peptides: Application of a monoreactive DTPA to DTPA-D-Phe1-octreotide synthesis. Bioconjugate Chem 1997, 8, 3, 442. |
| 【5】 Bakker, W.H.; et al.; [111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: Synthesis, radiolabeling and in vitro validation. Life Sci 1991, 49, 22, 1583. |
| 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) | 62878 | (4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-19-{[(2R)-2-amino-3-phenylpropanoyl]amino}-16-benzyl-7-[(1R)-1-hydroxyethyl]-N-[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacyclo | C49H66N10O10S2 | 详情 | 详情 | |
| (II) | 62879 | tert-butyl 4-[(4R,7S,10S,13R,16S,19R)-19-{[(2R)-2-amino-3-phenylpropanoyl]amino}-16-benzyl-7-[(1R)-1-hydroxyethyl]-4-({[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]amino}carbonyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17- | C54H74N10O12S2 | 详情 | 详情 | |
| (III) | 49150 | Diethylenetriaminepentaacetic acid; N,N-Bis[2-(2,6-dioxomorpholino)ethyl]glycine | 23911-26-4 | C14H19N3O8 | 详情 | 详情 |
| (IV) | 62880 | 2-[{2-[((1R)-1-benzyl-2-{[(4R,7S,10S,13R,16S,19R)-16-benzyl-10-{4-[(tert-butoxycarbonyl)amino]butyl}-7-[(1R)-1-hydroxyethyl]-4-({[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]amino}carbonyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8 | C68H93N13O20S2 | 详情 | 详情 | |
| (V) | 62881 | (13R)-14-{[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-16-benzyl-7-[(1R)-1-hydroxyethyl]-4-({[(1R,2R)-2-hydroxy-1-(hydroxymethyl)propyl]amino}carbonyl)-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-19-yl]am | C63H87N13O19S2 | 详情 | 详情 |