• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【药物名称】CGP-64222

【化学名称】N-(6-Aminohexyl)glycyl-[N-(3-guanidinopropyl)]glycyl-[N-(3-guanidinopropyl)]glycyl-(N-benzyl)glycyl-[N-(3-guanidinopropyl)]glycyl-D-lysyl-D-lysyl-D-arginyl-D-prolinamide

【CA登记号】186380-62-1

【 分 子 式 】C58H107N25O9

【 分 子 量 】1298.66159

【开发单位】Novartis (Originator)

【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Tat Inhibitors

合成路线1

The title compound was prepared by solid-phase peptide synthesis starting from N-Fmoc-D-proline linked to Rink resin (I). Deprotection of the Fmoc group by means of piperidine in DMA afforded proline-resin (II). Coupling of N-alpha-Fmoc-NG-Pmc-D-arginine (III) to proline-resin (II) using diisopropyl carbodiimide (DIC) and HOBt, followed by Fmoc deprotection with piperidine in DMA, furnished dipeptide-resin (IV). Further coupling and deprotection cycles incorporating the amino acid N2-Fmoc-N6-Boc-D-lysine (V) (twice) and the peptoid residue N-Fmoc-N-[3-(3-Pmc-guanidino)propyl]glycine (VIII) yielded the peptide resins (VI), (VII) and (IX), respectively.

1 Hamy, F.; et al.; An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences of the United States of America 1997, 94, 8, 3548.
2 Felder, E.; Hamy, F.; Heizmann, G.; Klimkait, T.; Lazdins, J.K. (Novartis AG); Antiviral peptoid cpds.. EP 0832110; WO 9640759 .
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) 42841 9H-fluoren-9-ylmethyl (2R)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate C20H20N2O3 详情 详情
(II) 37077 (2R)-2-pyrrolidinecarboxamide C5H10N2O 详情 详情
(III) 19035 (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4-dihydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoic acid 119831-72-0 C35H42N4O7S 详情 详情
(IV) 42842 (2R)-1-[(2R)-2-amino-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoyl]-2-pyrrolidinecarboxamide C25H42N6O5S 详情 详情
(V) 42847 (2R)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid C26H32N2O6 详情 详情
(VI) 42843 tert-butyl (5R)-5-amino-6-([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)-6-oxohexylcarbamate C36H62N8O8S 详情 详情
(VII) 42844 tert-butyl (5R)-5-amino-6-([(1R)-1-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-5-[(tert-butoxycarbonyl)amino]pentyl C47H82N10O11S 详情 详情
(VIII) 42845 2-([(9H-fluoren-9-ylmethoxy)carbonyl][3-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]propyl]amino)acetic acid C35H44N4O7S 详情 详情
(IX) 42846 tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-8-[4-[(tert-butoxycarbonyl)amino]butyl]-17-imino-7 C67H114N14O15S2 详情 详情

合成路线2

Further coupling and deprotection cycles incorporating peptoid N-Fmoc-N-benzylglycine (X), and twice peptoid (VIII), yielded the peptoid-resins (XI) and (XII), respectively. Bromoacetic acid (XIII) was subsequently coupled to resin (XII) to afford the bromoacetamido peptoid-resin (XIV).

1 Hamy, F.; et al.; An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences of the United States of America 1997, 94, 8, 3548.
2 Felder, E.; Hamy, F.; Heizmann, G.; Klimkait, T.; Lazdins, J.K. (Novartis AG); Antiviral peptoid cpds.. EP 0832110; WO 9640759 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIII) 42845 2-([(9H-fluoren-9-ylmethoxy)carbonyl][3-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]propyl]amino)acetic acid C35H44N4O7S 详情 详情
(IX) 42846 tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-8-[4-[(tert-butoxycarbonyl)amino]butyl]-17-imino-7 C67H114N14O15S2 详情 详情
(X) 42848 2-[benzyl[(9H-fluoren-9-ylmethoxy)carbonyl]amino]acetic acid C24H21NO4 详情 详情
(XI) 42849 tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-12-[2-(benzylamino)acetyl]-8-[4-[(tert-butoxycarbo C76H123N15O16S2 详情 详情
(XII) 42850   C116H187N23O24S4 详情 详情
(XIII) 23660 2-Bromoacetic acid 79-08-3 C2H3BrO2 详情 详情
(XIV) 42851   C118H188BrN23O25S4 详情 详情

合成路线3

Displacement of the bromine of (XIV) with N-Boc-1,6-diaminohexane (XV) produced resin (XVI). Finally, the side-chain protecting groups of (XVI) were cleaved and the desired peptoid was liberated from the resin by treatment with trifluoroacetic acid.

1 Hamy, F.; et al.; An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences of the United States of America 1997, 94, 8, 3548.
2 Felder, E.; Hamy, F.; Heizmann, G.; Klimkait, T.; Lazdins, J.K. (Novartis AG); Antiviral peptoid cpds.. EP 0832110; WO 9640759 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIV) 42851   C118H188BrN23O25S4 详情 详情
(XV) 31638 tert-butyl 6-aminohexylcarbamate 51857-17-1 C11H24N2O2 详情 详情
(XVI) 42852 tert-butyl (23R,26R)-26-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-16-benzyl-23-[4-[(tert-butoxycarbonyl)amino]but C129H211N25O27S4 详情 详情
Extended Information