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【结 构 式】 
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【药物名称】L-054522 【化学名称】N-[4-(2-Oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-ylcarbonyl]-[3(S)-methyl]-D-tryptophyl-L-lysine tert-butyl ester 【CA登记号】214348-67-1 【 分 子 式 】C35H47N7O5 【 分 子 量 】645.80874 |
【开发单位】Merck & Co. (Originator) 【药理作用】ENDOCRINE DRUGS, Pituitary Disorder Therapy, Treatment of Growth Hormone Excess, Treatment of Growth Hormone Secretion Disorders, Somatostatin SRIF1A (sst2) Agonists |
合成路线1
Coupling of N-Boc-beta-methyltryptophan (I) with N-Cbz-lysine tert-butyl ester (II) using EDC and HOBt afforded dipeptide (III). Selective deprotection of the Boc group of (III) with methanesulfonic acid gave amine (IV). This was converted to urea (VI) upon treatment with benzimidazolylpiperidine (V) and N,N'-disuccinimidyl carbonate in the presence of diisopropyl ethylamine. The N-carbobenzoxy group of (VI) was finally deprotected by hydrogenolysis over Pd/C.
| 【1】 Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2. Proc Natl Acad Sci USA 1998, 95, 18, 10836. |
| 【2】 Berk, S.; Yang, L.; Chen, M.H.; Johnston, D.; Pasternak, A.; Chapman, K.; Guo, L.; Nargund, R.; Tata, J.R.; Patchett, A.A. (Merck & Co., Inc.); Somatostatin agonists. EP 0984779; US 6063796; WO 9844922 . |
| 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) | 28255 | (2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)butyric acid | C17H22N2O4 | 详情 | 详情 | |
| (II) | 21879 | tert-butyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate | C18H28N2O4 | 详情 | 详情 | |
| (III) | 28256 | tert-butyl (2S)-6-[[(benzyloxy)carbonyl]amino]-2-[[(2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)butanoyl]amino]hexanoate | C35H48N4O7 | 详情 | 详情 | |
| (IV) | 28257 | tert-butyl (2S)-2-[[(2R,3S)-2-amino-3-(1H-indol-3-yl)butanoyl]amino]-6-[[(benzyloxy)carbonyl]amino]hexanoate | C30H40N4O5 | 详情 | 详情 | |
| (V) | 12138 | 1-(4-Piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one; 4-(2-Keto-1-benzimidazolinyl)piperidine | 20662-53-7 | C12H15N3O | 详情 | 详情 |
| (VI) | 28258 | tert-butyl (2S)-6-[[(benzyloxy)carbonyl]amino]-2-[[(2R,3S)-3-(1H-indol-3-yl)-2-([[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinyl]carbonyl]amino)butanoyl]amino]hexanoate | C43H53N7O7 | 详情 | 详情 |