Boc-L-phenylalanyl-N^im-Boc-L-histidine | 105116-50-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc-L-phenylalanyl-N^im-Boc-L-histidine
• 英文别名: Boc-Phe-His(1-Boc)-OH；(2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-3-[1-[(2-methylpropan-2-yl)oxycarbonyl]imidazol-4-yl]propanoic acid
• CAS: 105116-50-5
• 化学式: C₂₅H₃₄N₄O₇
• 分子量: 502.568
• InChiKey: QPVYXNKFJMVTMI-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  149
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Boc-L-phenylalanyl-N^im-Boc-L-histidine 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 35.0h， 生成 {1-[1-{1-Cyclohexylmethyl-2-hydroxy-3-[(2-morpholin-4-yl-ethylcarbamoyl)-methanesulfonyl]-propylcarbamoyl}-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester; hydrate
  参考文献：
  名称：

  Inhibitors of human renin with C-termini derived from amides and esters of .alpha.-mercaptoalkanoic acids

  摘要：

  New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration.

  DOI：

  10.1021/jm00093a009

文献信息

• Renin inhibiting polypeptides and intermediates therefor
  申请人：PFIZER INC.

  公开号：EP0211580A2

  公开（公告）日：1987-02-25

  Polypeptides and derivatives thereof containing oxa- and azahomocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.

  含有oxa-和azahomocyclostatine的多肽及其衍生物可用于抑制肾素酶的血管紧张素原分解作用。
• Renin inhibitors containing C-termini derived from mercaptoheterocycles
  作者：Wallace T. Ashton、Christine L. Cantone、Laura C. Meurer、Richard L. Tolman、William J. Greenlee、Arthur A. Patchett、Robert J. Lynch、Terry W. Schorn、John F. Strouse、Peter K. S. Siegl

  DOI：10.1021/jm00089a023

  日期：1992.5

  A series of transition-state analogues having heterocyclylthio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.
• KLEINMAN, EDWARD F.;ROSATI, ROBERT L.;BINDRA, JASJIT S.
  作者：KLEINMAN, EDWARD F.、ROSATI, ROBERT L.、BINDRA, JASJIT S.

  DOI：——

  日期：——
• US4599198A
  申请人：——

  公开号：US4599198A

  公开（公告）日：1986-07-08
• US4668769A
  申请人：——

  公开号：US4668769A

  公开（公告）日：1987-05-26