(R)-phosphotryptophan diethyl ester | 219922-15-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (R)-phosphotryptophan diethyl ester
• 英文别名: L-phosphotryptophan diethyl ester；(R)-H-Trp^p(OEt)2；(1R)-1-diethoxyphosphoryl-2-(1H-indol-3-yl)ethanamine
• CAS: 219922-15-3
• 化学式: C₁₄H₂₁N₂O₃P
• 分子量: 296.306
• InChiKey: UWBAVKPWFCHBPQ-CQSZACIVSA-N

物化性质

• 沸点：
  478.3±40.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  77.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-phosphotryptophan diethyl ester 在 palladium on activated charcoal ammonium formate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 N-[N-(N-tert-butoxycarbonyl-D-prolyl)-L-leucyl]-L-phosphotryptophan diethyl ester
  参考文献：
  名称：

  Synthesis and evaluation of new tripeptide phosphonate inhibitors of MMP-8 and MMP-2

  摘要：

  The phosphotryptophan derivative L-Pro-L-LeU-L-(P)Trp(OH)(2) (2b) was reported as the first example of left-hand-side(1) phosphonate inhibitor of MMP-8. Its uncommon mode of binding to MMP-8 was mainly ascribed to the presence of the proline residue in P, Ten new analogues of 2b were obtained by replacement of the aminoterminal L-Pro with aminoacid residues bearing small side chains. Most of the new analogues show an increase of affinity for MMP-2 and MMP-8, and different profiles of selectivity. Computer simulations were performed to explain the effects of substitutions on the preferred mode of binding. They reveal that most of the new analogues are probably accommodated in the right. rather than left-hand side of MMP-8 active site. (c) 2005 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.10.013
• 作为产物：
  描述：

  diethyl 1-amino-2-(3-indolyl)ethanephosphonate 生成 (R)-phosphotryptophan diethyl ester
  参考文献：
  名称：

  长春碱的新的α-氨基膦酸衍生物：化学和抗肿瘤活性。

  摘要：

  合成了长春碱的一系列新的氨基膦酸衍生物（1，VLB），并在体内和体外测试了其抗肿瘤活性。该化合物获自O4-脱乙酰基-VLB叠氮化物。研究的所有新产品均具有体外抑制微管蛋白聚合的能力。最有效的抗肿瘤化合物在膦酸酯上带有烷基取代基。在这些化合物中，抗肿瘤活性强烈取决于膦酸酯的立体化学。膦酸酯（1S）-[1-[（O4-脱乙酰基-3-脱（甲氧基羰基）vincaleukoblastin-3-基]羰基]氨基] -2-甲基丙基]膦酸二乙酯对癌细胞系均表现出显着活性。体外和体内。

  DOI：

  10.1021/jm00111a012

文献信息

• Two Crystal Structures of Human Neutrophil Collagenase, One Complexed with a Primed- and the Other with an Unprimed-Side Inhibitor:  Implications for Drug Design
  作者：Enrico Gavuzzo、Giorgio Pochetti、Fernando Mazza、Carlo Gallina、Barbara Gorini、Silvana D'Alessio、Michael Pieper、Harald Tschesche、Paul A. Tucker

  DOI：10.1021/jm9909589

  日期：2000.9.1

  Two crystal structures of human neutrophil collagenase (HNC, MMP-8), one complexed with a primed- and the other with an unprimed-side inhibitor, were determined using synchrotron radiation at 100 K. Both inhibitors contain non-hydroxamate zinc-binding functions. The Pro-Leu-L-Trp(P)(OH)(2) occupies the unprimed region of the active site, furnishes new structural information regarding interaction between the catalytic zinc ion and the phosphonate group, and is the only example of occupation of the S-1 subsite of MMP-8 by the bulky tryptophan side chain. The (R)-2-(biphenyl-4-ylsulfonyl)-1,2,3,4-tetrahydroisochinolin-3-carboxylic acid, a conformationally constrained D-Tic derivative, accommodates its biphenyl substituent into the deep primary specificity S-1' subsite, inducing a widening of the entrance to this pocket; this modification of the protein, mainly consisting in a shift of the segment centered at Pro217, is observed for the first time in MMP-8 complexes. Cation-aromatic interactions can stabilize the formation of both complexes, and the beneficial effect of aromatic substituents in proximity of the catalytic zinc ion is discussed. The phosphonate group bound to either a primed- or unprimed-side inhibitor maintains the same relative position with respect to the catalytic zinc ion, suggesting that this binding function can be exploited for the design of combined inhibitors assembled to interact with both primed and unprimed regions of the active cleft.
• LAVIELLE, GILBERT;HAUTEFAYE, PATRICK;SCHAEFFER, CORINNE;BOUTIN, JEAN A.;C+, J. MED. CHEM., 34,(1991) N, C. 1998-2003
  作者：LAVIELLE, GILBERT、HAUTEFAYE, PATRICK、SCHAEFFER, CORINNE、BOUTIN, JEAN A.、C+

  DOI：——

  日期：——