{1-[1-[1-(1-Hydroxy-2-{2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester | 97920-11-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: {1-[1-[1-(1-Hydroxy-2-{2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-1-[[(3S,4S)-3-hydroxy-6-methyl-1-[[(2S,3S)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]amino]-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 97920-11-1
• 化学式: C₄₀H₅₈N₈O₇
• 分子量: 762.95
• InChiKey: IKTWAJYRQBBRIB-QTCSXKEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  55
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  217
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  BOC-L-脯氨酸 、 {1-[1-[1-(1-Hydroxy-2-{2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester 在 氰基磷酸二乙酯 、 三乙胺 、 三氟乙酸 作用下， 生成 tert-butyl (2S)-2-[[(2S)-1-[[(2S)-1-[[(3S,4S)-3-hydroxy-6-methyl-1-[[(2S,3S)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]amino]-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Renin inhibitors containing .psi.[CH2O] pseudopeptide inserts

  摘要：

  Renin inhibitors 2-4 with the D-Lys renin inhibitory peptide (RIP) sequence, but containing Leu psi[CH2O]Ala (2), Leu psi[CH2O]Val (3), and Leu psi[CH2O]Leu (4) at the P1-P1' site, were of a comparable potency to RIP. N-Terminal Boc-protected inhibitors containing Pro psi[CH2O]Phe in positions P4-P3 were potent inhibitors of renin, with Boc-Phe-Pro psi[CH2O]Phe-His-Leu psi[CH(OH)CH2]Val-Ile-(2-aminomethyl) pyridine (17) having an IC50 of 1.6 X 10(-9) M.

  DOI：

  10.1021/jm00398a029
• 作为产物：
  描述：

  N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 {1-[1-[1-(1-Hydroxy-2-{2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butylcarbamoyl]-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Renin inhibitors containing .psi.[CH2O] pseudopeptide inserts

  摘要：

  Renin inhibitors 2-4 with the D-Lys renin inhibitory peptide (RIP) sequence, but containing Leu psi[CH2O]Ala (2), Leu psi[CH2O]Val (3), and Leu psi[CH2O]Leu (4) at the P1-P1' site, were of a comparable potency to RIP. N-Terminal Boc-protected inhibitors containing Pro psi[CH2O]Phe in positions P4-P3 were potent inhibitors of renin, with Boc-Phe-Pro psi[CH2O]Phe-His-Leu psi[CH(OH)CH2]Val-Ile-(2-aminomethyl) pyridine (17) having an IC50 of 1.6 X 10(-9) M.

  DOI：

  10.1021/jm00398a029

文献信息

• Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone, and related analogs
  作者：Suvit Thaisrivongs、Donald T. Pals、Warren M. Kati、Steve R. Turner、Lisa M. Thomasco、William Watt

  DOI：10.1021/jm00160a048

  日期：1986.10

  Peptides that contain difluorostatine and difluorostatone residues have been shown to be potent inhibitors of the aspartyl protease renin. The readily hydrated fluoro ketone is proposed to mimic the tetrahedral intermediate that forms during the enzyme-catalyzed hydrolysis of a peptidic bond. It is suggested that the sp3-hybridized ketal acts as a transition-state analogue renin inhibitor. The fluoro

  已显示含有二氟他汀和二氟他酮残基的肽是天冬氨酰蛋白酶肾素的有效抑制剂。提议将易水合的氟代酮模拟在肽催化的酶催化水解过程中形成的四面体中间体。建议将sp3杂化的缩酮用作过渡态类似物肾素抑制剂。氟代酮显示出比相应的非氟代酮更有效的抑制剂，后者是伪底物。P1位点上更多的亲脂性侧链可以增强二氟他汀类似物的抑制能力，但这在二氟他酮系列中无法得到证实。另外，对于含二氟他酮的肽已经显示出高的肾素特异性。
• TENBRINK, RUTH E.;PALS, DONALD T.;HARRIS, DOUGLAS W.;JOHNSON, GARLAND A., J. MED. CHEM., 31,(1988) N 3, 671-677
  作者：TENBRINK, RUTH E.、PALS, DONALD T.、HARRIS, DOUGLAS W.、JOHNSON, GARLAND A.

  DOI：——

  日期：——