<1(R)-<(benzyloxycarbonyl)amino>-3-methylbutyl>phosphinic acid | 120707-56-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: <1(R)-<(benzyloxycarbonyl)amino>-3-methylbutyl>phosphinic acid
• 英文别名: (R)-{1-[(benzyloxycarbonyl)amino]-3-methylbutyl}phosphinic acid；[(1R)-3-methyl-1-(phenylmethoxycarbonylamino)butyl]phosphinic acid
• CAS: 120707-56-4
• 化学式: C₁₃H₂₀NO₄P
• 分子量: 285.28
• InChiKey: NHNCLFLVBPVRHX-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  <1(R)-<(benzyloxycarbonyl)amino>-3-methylbutyl>phosphinic acid 在 palladium on activated charcoal 三甲基氯硅烷 、 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 8.0h， 生成 methyl 2-phosphinyl>acetate
  参考文献：
  名称：

  Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bond

  摘要：

  The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Replacement of the scissile bond with the phosphinic analogue of Leu10-Val11 (1b) gave the most potent inhibitors, having IC50 = 7.5 x 10(-8) M for H-Pro-His-Pro-Phe-His-(1b)-Ile-His-Lys-OH and IC50 = 1.0 x 10(-7) M for Z-Arg-Arg-Pro-Phe-His-(1b)-Ile-His-NH2. The shorter phosphonic acid sequence Z-Pro-Phe-His-(1d) retained biological activity with an IC50 = 6.4 x 10(-6) M.

  DOI：

  10.1021/jm00127a041
• 作为产物：
  描述：

  [1-(N-benzyloxycarbonylamino)-3-methylbutyl]phosphinic acid 在 disodium hydrogenphosphate 、 Chiral AX QD-2 stationary phase 作用下， 以 甲醇 、 水 为溶剂， 生成 <1(R)-<(benzyloxycarbonyl)amino>-3-methylbutyl>phosphinic acid 、 ((S)-1-Benzyloxycarbonylamino-3-methyl-butyl)-phosphinic acid
  参考文献：
  名称：

  High-performance liquid chromatographic enantiomer separation and determination of absolute configurations of phosphinic acid analogues of dipeptides and their α-aminophosphinic acid precursors

  摘要：

  The enantiomers of N-benzyloxycarbonyl-phospinic pseudodipeptides and their N-benzyloxycarbonyl-alpha-aminophosphinic acid precursors as well as various other structural analogues were separated oil a set of cinchona alkaloid-derived chiral anion-exchangers by HPLC in the reversed-phase mode. Semi-preparative scale chromatography provided single enantiomers in 100 mg quantities. The configurations of the enantiomers were assigned indirectly by enantioselective chromatography on the basis of the elution order and was confirmed by enantiomeric reference compounds. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(03)00537-8

文献信息

• The Most Potent Organophosphorus Inhibitors of Leucine Aminopeptidase. Structure-Based Design, Chemistry, and Activity
  作者：Jolanta Grembecka、Artur Mucha、Tomasz Cierpicki、Paweł Kafarski

  DOI：10.1021/jm030795v

  日期：2003.6.1

  phosphinate dipeptide analogues, which were synthesized and evaluated as inhibitors of the enzyme. The in vitro kinetic studies for the phosphinate dipeptide analogues revealed that these compounds belong to the group of the most effective LAP inhibitors found so far. Their further modification at the P1 position resulted in more active inhibitors, hPheP[CH(2)]Phe and hPheP[CH(2)]Tyr (K(i) values 66 nM and

  描述了一类新型的非常有效的细胞溶质亮氨酸氨基肽酶（LAP）抑制剂，该酶是金属蛋白酶家族的成员。牛晶状亮氨酸氨肽酶与亮氨酸的膦酸类似物（LeuP）配合的X射线结构用于新型LAP抑制剂的基于结构的设计，并用于分析其与酶结合位点的相互作用。通过修饰LeuP结构中的膦酸基团以寻找结合在酶S'侧的取代基来设计抑制剂。这产生了两类化合物，膦酰胺和次膦酸酯二肽类似物，它们被合成并被评估为酶的抑制剂。次膦酸酯二肽类似物的体外动力学研究表明，这些化合物属于迄今为止发现的最有效的LAP抑制剂。它们在P1位置的进一步修饰产生了更具活性的抑制剂hPheP [CH（2）] Phe和hPheP [CH（2）] Tyr（四种非对映异构体的混合物的K（i）值分别为66 nM和67 nM ）。如果考虑所有包含模拟LAP催化的反应过渡态的磷原子的化合物，则这些抑制剂对酶的结合亲和力最高。为了评估设计的LAP抑制剂的选择性，对
• Berlicki; Mucha; Kafarski, Polish Journal of Chemistry, 2007, vol. 81, # 11, p. 1959 - 1962
  作者：Berlicki、Mucha、Kafarski

  DOI：——

  日期：——
• ALLEN, MARK C.;FUHRER, WALTER;TUCK, BRIAN;WADE, ROY;WOOD, JEANETTE M., J. MED. CHEM., 32,(1989) N, C. 1652-1661
  作者：ALLEN, MARK C.、FUHRER, WALTER、TUCK, BRIAN、WADE, ROY、WOOD, JEANETTE M.

  DOI：——

  日期：——