methyl (2R)-2-amino-3-(2-naphthyl)propanoate | 109063-69-6

• 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: methyl (2R)-2-amino-3-(2-naphthyl)propanoate
• 英文别名: D-3-(2-naphthyl)alanine methyl ester；D-2-naphthylalanine methyl ester；(R)-3-(2-naphthyl)alanine methyl ester；(R)-Methyl 2-amino-3-(naphthalen-2-yl)propanoate；methyl (2R)-2-amino-3-naphthalen-2-ylpropanoate
• CAS: 109063-69-6；136282-47-8；87900-21-8
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: NJPNWMZBNBROPE-CYBMUJFWSA-N

物化性质

• 沸点：
  367.7±22.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-amino-3-(2-naphthyl)propanoate 在 3 A molecular sieve 、 sodium cyanoborohydride 、 碳酸氢钠 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 (3R)-3-((2-naphthyl)methyl)piperazin-2-one
  参考文献：
  名称：

  New highly potent dipeptidic growth hormone secretagogues with low molecular weight

  摘要：

  Based on NN703, low molecular weight growth hormone secretagouges (GHSs) with a reduced number of hydrogen binding sites were designed by removal of the C-terminal amide group. The compounds were highly potent in combination with high efficacy in a rat pituitary cell assay, being characterized with EC50 values down to 0.8 nM. Selected compounds were tested in in vivo animal models. The oral bioavailability in dogs was 16-44%. Also, the ED50 values of the compounds were determined both in dog and swine. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00160-4
• 作为产物：
  描述：

  methyl (R)-2-tert-butoxycarbonylamino-3-(naphth-2-yl)propanoate 在 三氟乙酸 作用下， 生成 methyl (2R)-2-amino-3-(2-naphthyl)propanoate
  参考文献：
  名称：

  Structure-guided design of α-amino acid-derived Pin1 inhibitors

  摘要：

  The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC50 < 100 nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.090

文献信息

• Enantioselective synthesis of non-proteinogenic amino acids via metallated bis-lactim ethers of 2,5-diketopiperazines
  作者：Ulrich Schöllkopf

  DOI：10.1016/s0040-4020(01)91926-x

  日期：1983.1

  excess = asymmetric induction) of the adduct exceeds 95%. On hydrolysis the adducts are cleaved liberating the chiral auxiliary (used to build up the bis-lactim ether 1) and the target molecules, the optically active amino acid methyl esters of type 8,19,25 or 36. The two amino acid esters are separable either by fractional distillation or (eventually after further hydrolysis to amino acids) by chromatography

  2,5-二酮哌嗪的双-内酯醚1包含一个手性诱导中心，一个酸性CH键和两个易于水解的位点。他们用BuLi反应以得到类型的锂化合物4，15，19或32，其具有前手性的C原子。他们很容易添加亲电试剂（例如烷基化剂或羰基化合物），具有非同寻常的非对映异构性。在许多情况下，加合物的减值（de =非对映异构体过量=不对称诱导）超过95％。水解时，加合物被裂解释放出手性助剂（用于构建双内酰胺醚1）和目标分子，即8型旋光氨基酸甲基酯，19，25或36。两种氨基酸酯可通过分馏或（最终在进一步水解成氨基酸后）通过色谱法分离。讨论了过渡状态模型，该模型可以解释异常高的不对称诱导和诱导构型的可预测性。
• Compounds with growth hormone releasing properties
  申请人：Novo Nordisk A/S

  公开号：US06350767B1

  公开（公告）日：2002-02-26

  The present invention relates to compounds, compositions containing them, and their use for treating medical disorders resulting from a deficiency in growth hormone.

  本发明涉及化合物、含有这些化合物的组合物，以及它们用于治疗由生长激素缺乏引起的医学疾病的用途。
• Novel amide derivatives as growth hormone secretagogues
  申请人：Ishiyama Nobuo

  公开号：US20060014701A1

  公开（公告）日：2006-01-19

  Disclosed are the novel compounds as growth hormone secretagogues represented by the structural Formula I: wherein R 1 is, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted amino, X is —CO— or —SO 2 —, Y is: wherein n is an integer from 0-4, R 4 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, R 5 and R 6 are independently selected from hydrogen, substituted or unsubstituted alkyl, or R 5 and R 6 or R 4 and R 5 are taken together to form substituted or unsubstituted alkylene, R 2 is hydrogen, or substituted or unsubstituted alkyl, R 3 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, D is substituted or unsubstituted amino, substituted or unsubstituted alkoxy, or substituted or unsubstituted alkylthio, * represents an asymmetric center, and pharmaceutically acceptable salts and individual isomers thereof, which have growth hormone releasing activity in humans or animals.

  本发明揭示了一种作为生长激素分泌素的新化合物，其结构式为I：其中R1是取代或未取代的烷基、取代或未取代的环烷基、取代或未取代的烷氧基、取代或未取代的芳基、或取代或未取代的氨基，X为—CO—或—SO2—，Y为：其中n为0-4的整数，R4为氢、取代或未取代的烷基、取代或未取代的环烷基、取代或未取代的芳基，R5和R6独立地选自氢、取代或未取代的烷基，或R5和R6或R4和R5一起形成取代或未取代的烷基烯，R2为氢或取代或未取代的烷基，R3为取代或未取代的烷基、取代或未取代的环烷基、取代或未取代的芳基，D为取代或未取代的氨基、取代或未取代的烷氧基，或取代或未取代的烷硫基，*代表一个不对称中心，以及在人类或动物体内具有生长激素释放活性的药用可接受的盐和各个异构体。
• Molecular interaction sites of vimentin RNA and methods of modulating the same
  申请人：——

  公开号：US20030083483A1

  公开（公告）日：2003-05-01

  Methods for the identification of compounds which modulate, either inhibit or stimulate, biomolecules are provided. Nucleic acids, especially RNAs are preferred substrates for such modulation. The present methods are particularly powerful in that they provide novel combinations of techniques which give rise to compounds, usually “small” organic compounds, which are highly potent modulators of RNA and other biomolecular activity. In accordance with preferred aspects of the invention, very large numbers of compounds may be tested essentially simultaneously to determine whether they are likely to interact with a molecular interaction site and modulate the activity of the biomolecule. Pharmaceuticals, veterinary drugs, agricultural chemicals, industrial chemicals, research chemicals and many other beneficial compounds may be identified in accordance with embodiments of this invention.

  提供了用于识别调节生物分子的化合物的方法，可以抑制或刺激生物分子的活性。核酸，特别是RNA是这种调节的首选底物。这些方法特别强大，因为它们提供了新的技术组合，产生了通常是“小”有机化合物的高效调节剂，这些化合物高度调节RNA和其他生物分子的活性。根据发明的首选方面，可以同时测试大量的化合物，以确定它们是否可能与分子相互作用位点相互作用，并调节生物分子的活性。制药、兽药、农业化学品、工业化学品、研究化学品和许多其他有益的化合物可以根据本发明的实施方案进行识别。
• Nickel/Copper‐Cocatalyzed Asymmetric Benzylation of Aldimine Esters for the Enantioselective Synthesis of α‐Quaternary Amino Acids
  作者：Youbin Peng、Chongyu Han、Yicong Luo、Guanlin Li、Xiaohong Huo、Wanbin Zhang

  DOI：10.1002/anie.202203448

  日期：2022.6.7

  The first Ni/Cu cocatalyzed asymmetric benzylation of aldimine esters has been developed. DFT calculations revealed that the strong electrophilicity of the η3-benzylnickel intermediate enabled the reaction to proceed smoothly under base-free conditions. The method was applied to the synthesis of BIRT-377 analogues, the key intermediate of PD154075 and CI-988.

  已经开发了第一个 Ni/Cu 共催化的醛亚胺酯的不对称苄基化。DFT计算表明，η 3 -苄基镍中间体的强亲电性使反应在无碱条件下顺利进行。该方法应用于PD154075和CI-988的关键中间体BIRT-377类似物的合成。