Boc-Phe-His-Sta-Leu-4-amido-1-benzylpiperidide | 87691-51-8

• 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: Boc-Phe-His-Sta-Leu-4-amido-1-benzylpiperidide
• 英文别名: Boc-Phe-His-(S,S)Sta-Leu-ABP；{1-[1-(1-{2-[1-(1-Benzyl-piperidin-4-ylcarbamoyl)-3-methyl-butylcarbamoyl]-1-hydroxy-ethyl}-3-methyl-butylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-1-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-[(1-benzylpiperidin-4-yl)amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 87691-51-8
• 化学式: C₄₆H₆₈N₈O₇
• 分子量: 845.095
• InChiKey: HSZKRMBOKKRAQJ-HECCNADXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  61
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  207
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-Boc-1-(2,4-二硝基苯基)-L-组氨酸 在 盐酸 、 polystyrene-vinylbenzene resin 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 肼 、 亚硝酸异戊酯 作用下， 以 甲醇 为溶剂， 反应 15.25h， 生成 Boc-Phe-His-Sta-Leu-4-amido-1-benzylpiperidide
  参考文献：
  名称：

  Renin inhibitors. Statine-containing tetrapeptides with varied hydrophobic carboxy termini

  摘要：

  A series of statine-containing tetrapeptides, systematically modified at the carboxy terminus with various hydrophobic aromatic groups, is described. These compounds were tested in vitro for their ability to inhibit porcine, human plasma, and purified human kidney renins. These analogues help to define optimal binding aspects in a region of the enzyme that appears to be specific for spatial arrangement of aromatic groups. Replacement of the metabolically labile Phe amide with nonpeptidal groups proved possible while achieving inhibitory potency in the nanomolar range vs. porcine kidney renin. For the compounds 6i, 6m, and 6o, a large discrepancy in potency between the human plasma and the purified human kidney renin assays was observed. This disparity does not appear to be a consequence of a previously proposed plasma binding component.

  DOI：

  10.1021/jm00393a029

文献信息

• Novel renin inhibitors: synthesis of aminostatine and comparison with statine-containing analogues
  作者：Richard J. Arrowsmith、Keith Carter、John G. Dann、David E. Davies、C. John Harris、Judith A. Morton、Philip Lister、John A. Robinson、David J. Williams

  DOI：10.1039/c39860000755

  日期：——

  The synthesis of renin inhibitors containing a novel amino-analogue of statine is described and inhibitory potencies are compared with those of statine congeners; the crystal structure of the aminostatine derivative (6) is reported.

  描述了含有一种新的他汀类氨基酸类似物的肾素抑制剂的合成，并将其抑制能力与他汀类同系物进行了比较。报告了氨基他汀衍生物（6）的晶体结构。
• Renin inhibitors and methods for using same
  申请人：SCHERING CORPORATION

  公开号：EP0246381A1

  公开（公告）日：1987-11-25

  The rise in intraocular pressure associated with the use of steroidal anti-inflammatory drugs is controlled by use of a renin inhibitor.

  使用类固醇抗炎药会导致眼压升高，而使用肾素抑制剂则可控制眼压升高。
• Combination of an angiotensin II antagonist or renin inhibitor with a neutral endopeptidase inhibitor
  申请人：SCHERING CORPORATION

  公开号：EP0498361A2

  公开（公告）日：1992-08-12

  Treatment of hypertension or congestive heart failure with a combination of an angiotensin II antagonist or a renin inhibitor with a neutral endopeptidase inhibitor, pharmaceutical compositions comprising said combinations and kits for administering separate pharmaceutical compositions in combination are disclosed, wherein the angiotensin II antagonists include saralasin, sar 1, ile 8 angiotensin II, Dup 753, EXP 6155, EXP 6803 and PD 123319, the renin inhibitors include enalkrein, RO 42-5892, A 65317, CP 80794, ES 1005, ES 8891, SQ 34017, CGP 29287, CGP 38560, SR 43845, U-71038, A 62198, and A 64662, and the neutral endopeptidase inhibitors include N-[N-[1(S)-carboxyl-3-phenylpropyl]-(S)-phenylalanyl]-(S)-isoserine, N-[N-[((1S)-carboxy-2-phenyl)ethyl]-(S)-phenylalanyl]-β-alanine; N-[2(S)-mercaptomethyl-3-(2-methylphenyl)-propionyl]methionine, SQ 28603, UK 69578, SQ 29072, thiorphan, retro-thiorphan and phosphoramidon.

  本发明公开了用血管紧张素II拮抗剂或肾素抑制剂与中性内肽酶抑制剂的组合物治疗高血压或充血性心力衰竭的方法、包含所述组合物的药物组合物以及用于联合施用单独药物组合物的试剂盒，其中血管紧张素II拮抗剂包括saralasin、sar 1、ile 8 angiotensin II、Dup 753、EXP 6155、EXP 6803和PD 123319，肾素抑制剂包括enalkrein、RO 42-5892、A 65317、CP 80794和PD 123319、Dup 753、EXP 6155、EXP 6803 和 PD 123319，肾素抑制剂包括 enalkrein、RO 42-5892、A 65317、CP 80794、ES 1005、ES 8891、SQ 34017、CGP 29287、CGP 38560、SR 43845、U-71038、A 62198、和 A 64662，中性内肽酶抑制剂包括 N-[N-[1(S)-羧基-3-苯基丙基]-(S)-苯丙氨酰]-(S)-异丝氨酸、N-[N-[((1S)-羧基-2-苯基)乙基]-(S)-苯丙氨酰]-β-丙氨酸；N-[2(S)-巯甲基-3-(2-甲基苯基)-丙酰基]蛋氨酸、SQ 28603、UK 69578、SQ 29072、thiorphan、retro-thiorphan 和 phosphoramidon。
• Renin inhibitory peptides having Phe 13 deletion
  申请人：Merck & Co., Inc.

  公开号：EP0081783B1

  公开（公告）日：1985-06-19
• RENIN INHIBITORS AND METHODS FOR USING SAME
  申请人：SCHERING CORPORATION

  公开号：EP0243477A1

  公开（公告）日：1987-11-04