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【结 构 式】 
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【药物名称】AC-178335 【化学名称】N-Acetyl-D-histidyl-D-phenylalanyl-D-isoleucyl-D-arginyl-D-tryptophyl-D-phenylalaninamide 【CA登记号】212966-15-9 【 分 子 式 】C49H63N13O7 【 分 子 量 】946.13136 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】ENDOCRINE DRUGS, PHARMACOLOGICAL TOOLS, Pituitary Disorder Therapy, Treatment of Growth Hormone Deficiency, Treatment of Growth Hormone Secretion Disorders, Somatostatin SRIF1A (sst2) Antagonists |
合成路线1
This peptide has been obtained by by the usual method of solid phase resin starting from N-Boc-protected D-phenylalanine coupled to a methylbenzhydryl amine polystyrene resin (I) by successive cycles of Boc deprotection and coupling. The amino acid used were successively, N-Boc-D-tryptophan (II), N-Boc-D-arginine (IV), N-Boc-D-isoleucine (VI), N-Boc-D-phenylalanine (VIII) and N-Boc-D-histidine (X), yielding the intermediate peptide-resins (III), (V), (VII), (IX), and (XI). Finally, this last intermediate was deprotected and cleaved from the resin with HF, acetylated at the N-terminus and amidated at the C-terminus using standard methods.
| 【1】 Baumbach, W.R.; Carrick, T.A.; Pausch, M.H.; Bingham, B.; Carmignac, D.; Robinson, I.C.A.F.; Houghten, R.; Eppler, C.M.; Price, L.A.; Zysk, J.R.; A linear hexapeptide somatostatin antagonist blocks somatostatin activity in vitro and influences growth hormone release in rats. Mol Pharmacol 1998, 54, 5, 864. |
| 【2】 Houghten, R.A.; Baumbach, W.R. (American Cyanamid Co.); Peptides useful as somatostatin antagonists. EP 0863156 . |
| 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) | 28336 | tert-butyl (1R)-2-amino-1-benzyl-2-oxoethylcarbamate | C14H20N2O3 | 详情 | 详情 | |
| (II) | 16114 | N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid | 13139-14-5 | C16H20N2O4 | 详情 | 详情 |
| (III) | 28337 | tert-butyl (1R)-2-[[(1R)-2-amino-1-benzyl-2-oxoethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamate | C25H30N4O4 | 详情 | 详情 | |
| (IV) | 28344 | (2R)-5-[[amino(imino)methyl]amino]-2-[(tert-butoxycarbonyl)amino]pentanoic acid | C11H22N4O4 | 详情 | 详情 | |
| (V) | 28338 | tert-butyl (1R)-1-([[(1R)-2-[[(1R)-2-amino-1-benzyl-2-oxoethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]amino]carbonyl)-4-[[amino(imino)methyl]amino]butylcarbamate | C31H42N8O5 | 详情 | 详情 | |
| (VI) | 28339 | (2R,3R)-2-[(tert-butoxycarbonyl)amino]-3-methylpentanoic acid | C11H21NO4 | 详情 | 详情 | |
| (VII) | 28340 | tert-butyl (1R,2R)-1-[[((1R)-1-([[(1R)-2-[[(1R)-2-amino-1-benzyl-2-oxoethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]amino]carbonyl)-4-[[amino(imino)methyl]amino]butyl)amino]carbonyl]-2-methylbutylcarbamate | C37H53N9O6 | 详情 | 详情 | |
| (VIII) | 22184 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid | C14H19NO4 | 详情 | 详情 | |
| (IX) | 28341 | tert-butyl (1R,4R,7R,10R,13R)-14-amino-7-(3-[[amino(imino)methyl]amino]propyl)-1,13-dibenzyl-10-(1H-indol-3-ylmethyl)-4-[(1R)-1-methylpropyl]-2,5,8,11,14-pentaoxo-3,6,9,12-tetraazatetradec-1-ylcarbamate | C46H62N10O7 | 详情 | 详情 | |
| (X) | 28342 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(1H-imidazol-5-yl)propionic acid | 50654-94-9 | C11H17N3O4 | 详情 | 详情 |
| (XI) | 28343 | tert-butyl (1R,4R,7R,10R,13R,16R)-17-amino-10-(3-[[amino(imino)methyl]amino]propyl)-4,16-dibenzyl-1-(1H-imidazol-5-ylmethyl)-13-(1H-indol-3-ylmethyl)-7-[(1R)-1-methylpropyl]-2,5,8,11,14,17-hexaoxo-3,6,9,12,15-pentaazaheptadec-1-ylcarbamate | C52H69N13O8 | 详情 | 详情 |