O-benzyl-PhTX-343 | 130203-14-4

• 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: O-benzyl-PhTX-343
• 英文别名: N-Butyryl-O-benzyl-L-tyrosine-spermineamide；N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]butanamide
• CAS: 130203-14-4
• 化学式: C₃₀H₄₇N₅O₃
• 分子量: 525.735
• InChiKey: FXFSATURWLJOST-NDEPHWFRSA-N

物化性质

• 沸点：
  768.3±60.0 °C(Predicted)
• 密度：
  1.077±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  38
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O-benzyl-PhTX-343 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以99%的产率得到蜂毒毒素343三-三氟乙酸盐
  参考文献：
  名称：

  Synthesis of glutamate receptor antagonist philanthotoxin-433 (PhTX-433) and its analogs

  摘要：

  DOI：

  10.1016/s0040-4020(01)85463-6
• 作为产物：
  描述：

  Boc-O-苄基-L-酪氨酸 在 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 8.0h， 生成 O-benzyl-PhTX-343
  参考文献：
  名称：

  Synthesis of glutamate receptor antagonist philanthotoxin-433 (PhTX-433) and its analogs

  摘要：

  DOI：

  10.1016/s0040-4020(01)85463-6

文献信息

• Design, Synthesis, and Biological Evaluation of Symmetrically and Unsymmetrically Substituted Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists
  作者：Michela Rosini、Roberta Budriesi、M. Gabriele Bixel、Maria L. Bolognesi、Alberto Chiarini、Ferdinand Hucho、Povl Krogsgaard-Larsen、Ian R. Mellor、Anna Minarini、Vincenzo Tumiatti、Peter N. R. Usherwood、Carlo Melchiorre

  DOI：10.1021/jm991110n

  日期：1999.12.1

  The universal template approach to drug design foresees that a polyamine can be modified in such a way to recognize any neurotransmitter receptor. Thus, hybrids of polymethylene tetraamines and philanthotoxins, exemplified by methoctramine (1) and PhTX-343 (2), respectively, were synthesized to produce novel inhibitors of muscular nicotinic acetylcholine receptors. Polyamines 3-25 were synthesized and their biological profiles were evaluated at frog rectus abdominis muscle nicotinic receptors and guinea pig left atria (M-2) and ileum longitudinal muscle (M-3) muscarinic acetylcholine receptors. All of the compounds, like prototypes 1 and 2, were noncompetitive antagonists of nicotinic receptors while being, like 1, competitive antagonists at,muscarinic M-2 and M-3 receptor subtypes. interestingly, polyamines bearing a low number of methylenes between the nitrogen atoms, as in 3, 6, and 7, displayed a biological profile similar to that of 2: a noncompetitive antagonism at nicotinic receptors in the 7-25 mu M range while not showing any antagonism for muscarinic receptors up to 10 mu M. increasing the number of methylenes separating these nitrogen atoms in methoctramine related tetraamines resulted in a significant improvement; in potency at nicotinic receptors. The most potent tetraamine was 19, bearing a 12 methylene spacer between the nitrogen atoms, which was 12-fold and 250-fold more potent than prototypes 1 and 2, respectively. Tetraamines 9-11, bearing a rather rigid spacer between the nitrogen atoms instead of the very flexible polymethylene chain, displayed a profile similar to that of 1 at nicotinic receptors, whereas a significant decrease in potency was observed at muscarinic M-2 receptors. This finding may have relevance in understanding the mode of interaction with these receptors. Similarly, the constrained analogue 12 of methoctramine showed a decrease in potency at nicotinic and muscarinic M-2 receptors, revealing that the tricyclic system, which incorporates the 2-methoxybenzylamine moiety of 1, does not represent a good pharmacophore for activity at these sites. A most intriguing finding was the observation that the photolabile tetraamine 22 was more potent than methoctramine at nicotinic receptors and, what is more important, it inhibited a closed stale of the receptor.
• Synthesis and binding of [125I2]philanthotoxin-343, [125I2]philanthotoxin-343-lysine, and [125I2]philanthotoxin-343-arginine to rat brain membranes
  作者：R. A. Goodnow、R. Bukownik、K. Nakanishi、P. N. R. Usherwood、A. T. Eldefrawi、N. A. Anis、M. E. Eldefrawi

  DOI：10.1021/jm00112a012

  日期：1991.8

  I-125(2)-iodinated philanthotoxin-343 (PhTX-343) (10), [I-125(2)]PhTX-343-arginine (11), and [I-125(2)]PhTX-343-lysine (12) were synthesized and evaluated as probes for glutamate receptors in rat brain synaptic membranes. It was found that these probes were not specific for the glutamate receptors but may be useful for investigating the polyamine binding site. Filtration assays with Whatman GF/B fiber glass filters were unsuitable because the iodinated PhTX-343 analogues exhibited high nonspecific binding to the filters, thus hindering detection of specific binding to membranes. When binding was measured by a centrifugal assay, [I-125(2)]PhTX-343-lysine (12) bound with low affinity (K(D) = 11.4 +/- 2-mu-M) to a large number of sites (37.2 +/- 9.1 nmol/mg of protein). The binding of [I-125(2)]PhTX-343-lysine was sensitive only to the polyamines spermine and spermidine, which displaced [I-125(2)]PhTX-343-lysine (12) with K(i) values of (3.77 +/- 1.4) X 10(-5) M and (7.51 +/- 0.77) X 10(-5) M, respectively. The binding was insensitive to glutamate receptor agonists and antagonists. Binding results with [I-125(2)]PhTX-343-arginine (11) were similar to those of [I-125(2)]PhTX-343-lysine. Considering the high number of toxin binding sites (10000-fold more than glutamate) in these membranes and the insensitivity of the binding to almost all drugs that bind to glutamate receptors, it is evident that most of the binding observed is not to glutamate receptors. On the other hand, PhTX analogues with photoaffinity labels may be useful in the isolation/purification of various glutamate and nicotinic acetylcholine receptors; they could also be useful in structural studies of receptors and their binding sites.
• GOODNOW, R. (JR);KONNO, K.;NIWA, M.;KALLIMOPOULOS, T.;BUKOWNIK, R.;LENARE+, TETRAHEDRON, 46,(1990) N, C. 3267-3286
  作者：GOODNOW, R. (JR)、KONNO, K.、NIWA, M.、KALLIMOPOULOS, T.、BUKOWNIK, R.、LENARE+

  DOI：——

  日期：——
• NAKANISHI, KOJI;GOODNOW, R.;KONNO, K.;NIWA, M.;BUKOWNIK, RUDOLPH;KALLIMOP+, PURE AND APPL. CHEM., 62,(1990) N, C. 1223-1230
  作者：NAKANISHI, KOJI、GOODNOW, R.、KONNO, K.、NIWA, M.、BUKOWNIK, RUDOLPH、KALLIMOP+

  DOI：——

  日期：——
• GOODNOW, R. A. (JR);BUKOWNIK, R.;NAKANISHI, K.;USHERWOOD, P. N. R.;ELDEFR+, J. MED. CHEM., 34,(1991) N, C. 2389-2394
  作者：GOODNOW, R. A. (JR)、BUKOWNIK, R.、NAKANISHI, K.、USHERWOOD, P. N. R.、ELDEFR+

  DOI：——

  日期：——