N-butyryl-O-benzyl-L-tyrosine p-nitrophenyl ester | 125376-03-6

• 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: N-butyryl-O-benzyl-L-tyrosine p-nitrophenyl ester
• 英文别名: 3-(4-benzyloxy-phenyl)-2-butyrylamino-propionic acid 4-nitro-phenyl ester；N-butyryl-O-benzyl-L-tyrosine-p-nitrophenol ester；(4-nitrophenyl) (2S)-2-(butanoylamino)-3-(4-phenylmethoxyphenyl)propanoate
• CAS: 125376-03-6
• 化学式: C₂₆H₂₆N₂O₆
• 分子量: 462.502
• InChiKey: UFXJEKSUWCXZSR-DEOSSOPVSA-N

物化性质

• 沸点：
  692.0±55.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-butyryl-O-benzyl-L-tyrosine p-nitrophenyl ester 在 palladium dihydroxide 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 20.0~35.0 ℃ 、101.33 kPa 条件下， 反应 84.0h， 生成 (4-{7-[2-butyrylamino-3-(4-hydroxy-phenyl)-propionylamino]-heptylamino}-butyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  A Subtype-Selective, Use-Dependent Inhibitor of Native AMPA Receptors

  摘要：

  AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors (AMPARs) are glutamate-gated ion channels that play central roles in the mammalian brain, mediating fast excitatory synaptic transmission and underlying several forms of synaptic plasticity. Two subtypes of AMPARs are primarily coexpressed at excitatory synapses in adult animals (GluR1/2 and GluR2/3 receptors). Efforts to distinguish between the potentially distinct roles these receptor subtypes play at synapses have been hampered by the absence of a subtype-selective AMPAR antagonist. Here we show that the polyamine philanthotoxin-7,4 (PhTx-74) is a subtype-selective AMPAR antagonist, inhibiting GluR1/2, but not GluR2/3 receptors, use-dependently. The molecular basis for the observed selectivity and a highly efficient synthesis of this remarkable toxin are also presented. PhTx-74 provides the first a means of directly monitoring subtype-specific changes in the composition of AMPARs at native synapses, including during hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to share processes related to learning and memory.

  DOI：

  10.1021/ja0705801
• 作为产物：
  描述：

  methyl 2S-amino-3-(4-benzyloxyphenyl)propionate hydrochloride 在 lithium hydroxide 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 36.0h， 生成 N-butyryl-O-benzyl-L-tyrosine p-nitrophenyl ester
  参考文献：
  名称：

  A Subtype-Selective, Use-Dependent Inhibitor of Native AMPA Receptors

  摘要：

  AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors (AMPARs) are glutamate-gated ion channels that play central roles in the mammalian brain, mediating fast excitatory synaptic transmission and underlying several forms of synaptic plasticity. Two subtypes of AMPARs are primarily coexpressed at excitatory synapses in adult animals (GluR1/2 and GluR2/3 receptors). Efforts to distinguish between the potentially distinct roles these receptor subtypes play at synapses have been hampered by the absence of a subtype-selective AMPAR antagonist. Here we show that the polyamine philanthotoxin-7,4 (PhTx-74) is a subtype-selective AMPAR antagonist, inhibiting GluR1/2, but not GluR2/3 receptors, use-dependently. The molecular basis for the observed selectivity and a highly efficient synthesis of this remarkable toxin are also presented. PhTx-74 provides the first a means of directly monitoring subtype-specific changes in the composition of AMPARs at native synapses, including during hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to share processes related to learning and memory.

  DOI：

  10.1021/ja0705801

文献信息

• Butyryl-tyrosinyl spermine, analogs thereof and methods of preparing and
  申请人：The Trustees of Columbia University

  公开号：US06001824A1

  公开（公告）日：1999-12-14

  The present invention provides a compound having the structure: ##STR1## wherein R.sub.1 is a saturated or unsaturated linear or branched chain alkyl group, or a cholestanyl group; wherein R.sub.2 is a 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 4-hydroxyphenyl, 4-(arylalkyloxy)phenyl, 3,4-dihalophenyl, 4-hydroxy-3,5-dihalophenyl, 4-azidophenyl or 4-halophenyl group; wherein R.sub.3 is H, a linear or branched chain alkyl or alkenyl group, or a phenyl, 2-azidophenyl, 3-azidophenyl, 4-azidophenyl group, or an a alkenylacyl, 3-amino-3-butylpropyl, N-[N-(N-4-azidobenzoyl}aminopropyl) aminopropyl], cis- or trans-cinnamyl, 2-amino-2-[(4'-azidophenyl)acetyl, (trifluoromethyl)aminoacetyl or D- or L-arginyl group bonded through the .alpha.-carbonyl moiety thereof; R.sub.4 is H, or a linear or branched chain alkyl group; wherein R.sub.5, R.sub.6 and R.sub.7 are independently the same or different and are H, a linear or branched chain alkyl group, an aryl group or an arylalkyl group; wherein n, j and t are each 0 or 1; wherein m, o, p, q, r and s are independently the same or different and are 0, 1 or 2; wherein r+s and m+o are each equal to 2; wherein, if j is 0, p+q is 2; wherein, if j is 1, then p is 1, q is 0 and R.sub.6 is H; and wherein * denotes a D or L configuration. The invention also provides a method of synthesizing the compound. Another aspect of the invention concerns a method of treating a subject afflicted by a disorder associated with binding of an etiological agent to a glutamate receptor.

  本发明提供一种具有以下结构的化合物：##STR1## 其中 R.sub.1 是饱和或不饱和的直链或支链烷基基团，或者是胆固醇基团；其中 R.sub.2 是2-吲哚基、3-吲哚基、4-吲哚基、5-吲哚基、4-羟基苯基、4-(芳基烷氧基)苯基、3,4-二卤苯基、4-羟基-3,5-二卤苯基、4-偶氮苯基或4-卤苯基基团；其中 R.sub.3 是 H、直链或支链烷基或烯基基团，或苯基、2-偶氮苯基、3-偶氮苯基、4-偶氮苯基基团，或烯基酰基、3-氨基-3-丁基丙基、N-[N-(N-4-偶氮苯甲酰基}氨丙基)氨丙基]、顺式或反式肉桂基、2-氨基-2-[(4'-偶氮苯基)乙酰基、(三氟甲基)氨基乙酰基或 D- 或 L-精氨酰基通过其 α-羰基结合的；R.sub.4 是 H，或者是直链或支链烷基基团；其中 R.sub.5、R.sub.6 和 R.sub.7 独立地相同或不同且为 H、直链或支链烷基基团、芳基或芳基烷基基团；其中 n、j 和 t 每个都是 0 或 1；其中 m、o、p、q、r 和 s 独立地相同或不同且为 0、1 或 2；其中 r+s 和 m+o 每个都等于 2；其中，如果 j 是 0，则 p+q 是 2；其中，如果 j 是 1，则 p 是 1，q 是 0，且 R.sub.6 是 H；其中 * 表示 D 或 L 构型。该发明还提供一种合成该化合物的方法。该发明的另一个方面涉及一种治疗患有与疾病相关的病因体结合到谷氨酸受体的主体的方法。
• Structure−Activity Relationships of Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists. 2. Role of Polymethylene Chain Lengths Separating Amine Functions and of Substituents on the Terminal Nitrogen Atoms
  作者：Michela Rosini、M. Gabriele Bixel、Gabriella Marucci、Roberta Budriesi、Michael Krauss、Maria L. Bolognesi、Anna Minarini、Vincenzo Tumiatti、Ferdinand Hucho、Carlo Melchiorre

  DOI：10.1021/jm011067f

  日期：2002.4.1

  compounds, like prototype 1, were noncompetitive antagonists of nicotinic receptors while being competitive antagonists at M(2) and M(3) mAChRs. The biological profile of polyamines 4-7 revealed that increasing the number of amine functions and the chain length separating these nitrogen atoms led to a significant improvement in potency at nAChRs. Moreover, the role of the number and type of amine functions

  聚亚甲基四胺甲辛胺（1）是一种典型的抗毒蕈碱配体，对肌肉nAChR具有显着的亲和力。因此，根据通用模板方法，对1进行结构修饰以提高对肌肉型nAChR的亲和力和选择性。合成的多胺衍生物分别在蛙直肌和鱼雷nAChRs和豚鼠左心房（M（2））和回肠纵肌（M（3））mAChRs上进行测试。所有化合物，如原型1，都是烟碱样受体的非竞争性拮抗剂，同时是M（2）和M（3）mAChRs的竞争性拮抗剂。多胺4-7的生物学特性表明，增加胺官能团的数量和分隔这些氮原子的链长导致nAChRs的效力显着提高。此外，通过合成化合物9和10，进一步研究了胺官能团的数量和类型在与nAChRs相互作用中的作用，显示了四胺8和11，在氮原子之间带有相当刚性的间隔基，而不是非常柔软的聚亚甲基链，在nAChRs处的分布类似于1，而在mAChRs处观察到效力显着降低。带有2-甲氧基苯乙基的四胺12的效力比1低，而带有二苯乙基部分的
• Synthesis of glutamate receptor antagonist philanthotoxin-433 (PhTX-433) and its analogs
  作者：R. Goodnow、K. Konno、M. Niwa、T. Kallimopoulos、R. Bukownik、Deborah Lenares、K. Nakanishi

  DOI：10.1016/s0040-4020(01)85463-6

  日期：——
• Synthesis of philanthotoxin analogs with a branched polyamine moiety
  作者：Aristotle G. Kalivretenos、Koji Nakanishi

  DOI：10.1021/jo00076a017

  日期：1993.11

  Philanthotoxin (PhTX-433), a potent noncompetitive inhibitor of the L-glutamate receptors and the nicotinic acetylcholine receptors of vertebrates and invertebrates, has a butyryl-tyrosyl-thermo-spermine structure. Several synthetic analogs of PhTX with hydrophobic alkyl branches in the polyamine chain exhibit 6- to 10-fold enhanced activities to various receptors. Because the branched analogs exhibit such unique activities and because of their importance in tertiary structural studies of ligand/receptor binding, methods for preparing branched PhTX analogs, including photolabile analogs, are presented.
• Structure-binding relation of philanthotoxins from nicotinic acetylcholine receptor binding assay
  作者：Koji Nakanishi、Xuefei Huang、Hong Jiang、Ying Liu、Kan Fang、Danwen Huang、Seok-Ki Choi、Elizabeth Katz、Mohyee Eldefrawi

  DOI：10.1016/s0968-0896(97)00137-5

  日期：1997.10

  Philanthotoxins are noncompetitive inhibitors of the nicotinic acetylcholine receptor and the Various glutamate receptors. Analogues carrying photoaffinity labels, fluorine atoms for solid-state NMR studies of ligand/receptor interaction, and large head groups such as porphyrins and planar bulky aromatic rings (BIG analogues) for clarifying mode of entry and orientation of analogues in receptors have been synthesized, assayed against the nicotinic acetylcholine receptor, and brief comments are given for the assay results. (C) 1997 Elsevier Science Ltd.