【结 构 式】 |
【药物名称】99mTc-EC-AMDP 【化学名称】[1-[N-[2-[1(R)-Carboxy-2-sulfanylethylamino]ethyl]-L-cysteinylamino]methyl-1,1-diphosphonic acid]oxo[99mTc]technetium(V) complex 【CA登记号】 【 分 子 式 】C9H18N3O10P2S2Tc 【 分 子 量 】553.33351 |
【开发单位】Katholieke Universiteit Leuven (Originator), Rega Institute for Medical Research (Originator) 【药理作用】DIAGNOSTIC AGENTS, Radiopharmaceuticals, Technetium Complexes |
合成路线1
Alkylation of the sodium derivative of 1,2-ethylene dicysteine (I) with benzyl chloride in liquid ammonia affords the S,S'-dibenzyl compound (II). Subsequent protection of the amino groups of (II) with benzyl chloroformate provides the bis-carbamate (III). Esterification of diacid (III) with one equivalent of MeOH in the presence of DCC and DMAP furnishes the mono-methyl ester (IV). This is then coupled with 1-aminomethylenediphosphonic acid tetraethyl ester (V) to yield amide (VI). The ethyl phosphonate ester groups of (VI) are selectively cleaved by means of trimethylsilyl bromide, producing diphosphonic acid (VII). Further hydrolysis of the methyl carboxylate ester group of (VII) under basic conditions leads to acid (VIII). Then, simultaneous removal of the S-benzyl and N-Cbz protecting groups of (VIII) is accomplished by means of Na in liquid ammonia to furnish dithiol (IX). This is finally complexed with [99mTc] sodium pertechnetate in the presence of SnCl2 to produce the target technetium conjugate.
【1】 Verbeke, K.; et al.; Development of a conjugate of 99mTc-EC with aminomethylenediphosphonate in the search for a bone tracer with fast clearance from soft tissue. Bioconjugate Chem 2002, 13, 1, 16. |
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) | 12945 | (2R)-2-[(2-[[(1R)-1-Carboxy-2-sulfanylethyl]amino]ethyl)amino]-3-sulfanylpropionic acid | C8H16N2O4S2 | 详情 | 详情 | |
(II) | 61689 | (2R)-3-(benzylsulfanyl)-2-[(2-{[(1R)-2-(benzylsulfanyl)-1-carboxyethyl]amino}ethyl)amino]propanoic acid | C22H28N2O4S2 | 详情 | 详情 | |
(III) | 61690 | (2R)-2-[[(benzyloxy)carbonyl](2-{[(benzyloxy)carbonyl][(1R)-2-(benzylsulfanyl)-1-carboxyethyl]amino}ethyl)amino]-3-(benzylsulfanyl)propanoic acid | C38H40N2O8S2 | 详情 | 详情 | |
(IV) | 61691 | (2R)-2-{[(benzyloxy)carbonyl][2-([(benzyloxy)carbonyl]{(1R)-1-[(benzylsulfanyl)methyl]-2-methoxy-2-oxoethyl}amino)ethyl]amino}-3-(benzylsulfanyl)propanoic acid | C39H42N2O8S2 | 详情 | 详情 | |
(V) | 23933 | 2-Propanamine; Isopropylamine | 75-31-0 | C3H9N | 详情 | 详情 |
(VI) | 61692 | methyl (8R,13R)-9,12-bis[(benzyloxy)carbonyl]-8,13-bis[(benzylsulfanyl)methyl]-5-(diethoxyphosphoryl)-4-ethoxy-4,7-dioxo-3-oxa-6,9,12-triaza-4lambda~5~-phosphatetradecan-14-oate | C48H63N3O13P2S2 | 详情 | 详情 | |
(VII) | 61693 | (4R,9R)-5,8-bis[(benzyloxy)carbonyl]-4,9-bis[(benzylsulfanyl)methyl]-3,10-dioxo-1-phosphono-11-oxa-2,5,8-triazadodec-1-ylphosphonic acid | C40H47N3O13P2S2 | 详情 | 详情 | |
(VIII) | 61694 | (5R,10R)-6,9-bis[(benzyloxy)carbonyl]-5,10-bis[(benzylsulfanyl)methyl]-1,1-dihydroxy-1,4-dioxo-2-phosphono-3,6,9-triaza-1lambda~5~-phosphaundecan-11-oic acid | C39H45N3O13P2S2 | 详情 | 详情 | |
(IX) | 61695 | (5R,10R)-1,1-dioxido-1,4-dioxo-2-phosphonato-5,10-bis(sulfidomethyl)-3,6,9-triaza-1lambda~5~-phosphaundecan-11-oate | C9H14N3O9P2S2 | 详情 | 详情 |