N-Boc-(S)-3',5'-dimethylphenylalanine | 849440-33-1

• 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-Boc-(S)-3',5'-dimethylphenylalanine
• 英文别名: N^α-tert-butyloxycarbonyl-3',5'-dimethyl-L-phenylalanine；N-(tert-butoxycarbonyl)-3,5-dimethyl-L-phenylalanine；Boc-Phe(3,5-Me)-OH；(2S)-3-(3,5-dimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 849440-33-1
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: YTXNDRYCIWRWPG-ZDUSSCGKSA-N

物化性质

• 熔点：
  106-110 °C(Solv: hexane (110-54-3); ethyl acetate (141-78-6))
• 沸点：
  452.2±45.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-Boc-(S)-3',5'-dimethylphenylalanine 在 N-甲基吗啉 、 lithium aluminium tetrahydride 、 双氧水 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 二甲基亚砜 为溶剂， 反应 46.0h， 生成 tert-butyl N-[(2S)-4-amino-1-(3,5-dimethylphenyl)-3-hydroxy-4-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  [EN] CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
  [FR] MODULATEURS DE CALPAIN ET LEURS UTILISATIONS THÉRAPEUTIQUES

  摘要：

  公开号：

  WO2018064119A8
• 作为产物：
  描述：

  3',5'-dimethyl-L-phenylalanine 、 二碳酸二叔丁酯 在 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以96.5%的产率得到N-Boc-(S)-3',5'-dimethylphenylalanine
  参考文献：
  名称：

  Bifunctional [2‘,6‘-Dimethyl-l-tyrosine]endomorphin-2 Analogues Substituted at Position 3 with Alkylated Phenylalanine Derivatives Yield Potent Mixed μ-Agonist/δ-Antagonist and Dual μ-Agonist/δ-Agonist Opioid Ligands

  摘要：

  Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) and [Dmt(1)]EM-2 (Dmt = 2',6'-dimethyl-L-tyrosine) analogues, containing alkylated Phe(3) derivatives, 2'-monomethyl (2, 2'), 3',5'- and 2',6'-dimethyl (3, 3', and 4', respectively), 2',4',6'-trimethyl (6, 6'), 2'-ethyl-6'-methyl (7, 7'), and 2'-isopropyl-6'-methyl (8, 8') groups or Dmt (5, 5'), had the following characteristics: (i) [Xaa(3)]EM-2 analogues exhibited improved mu- and delta-opioid receptor affinities. The latter, however, were inconsequential (K-i(delta) = 491-3451 nM). (ii) [Dmt(1),Xaa(3)]EM-2 analogues enhanced mu- and delta-opioid receptor affinities (K-i(mu) = 0.069-0.32 nM; K-i(delta) = 1.83-99.8 nM) without kappa-opioid receptor interaction. (iii) There were elevated mu-bioactivity (IC50 = 0.12-14.4 nM) and abolished delta-agonism (IC50 > 10 mu M in 2', 3', 4', 5', 6'), although 4' and 6' demonstrated a potent mixed mu-agonism/delta-antagonism (for 4', IC50 mu = 0.12 and pA(2) = 8.15; for 6', IC50 mu = 0.21 nM and pA(2) = 9.05) and 7' was a dual mu-agonist/delta-agonist (IC50 mu = 0.17 nM; IC50 delta = 0.51 nM).

  DOI：

  10.1021/jm061238m

文献信息

• [EN] SUBSTITUTED UREA DEPSIPEPTIDE ANALOGS AS ACTIVATORS OF THE CLPP ENDOPEPTIDASE<br/>[FR] ANALOGUES DE DEPSIPEPTIDE D'URÉE SUBSTITUÉS À UTILISER EN TANT QU'ACTIVATEURS DE L'ENDOPEPTIDASE CLPP
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2018045313A1

  公开（公告）日：2018-03-08

  In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators the ClpP endopeptidease; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及替代脲depsipeptide类似物，其衍生物以及相关化合物，这些化合物可用作激活ClpP内肽酶的活化剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗传染病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不意味着对本发明的限制。
• [EN] CATHEPSIN CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF VARIOUS DISEASES<br/>[FR] INHIBITEURS DE LA CATHEPSINE CYSTÉINE PROTÉASE POUR TRAITER DES MALADIES VARIÉES
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2010148488A1

  公开（公告）日：2010-12-29

  The present invention relates to compounds capable of inhibiting and/or decreasing the activity of one or more cathepsins, thereby treating and/or preventing various disease states associated with one or more cysteine proteases including, but not limited to, cathepsins and papain-like cysteine proteases. Disease states treated and/or prevented by the compounds of the invention include, but are not limited to, mammalian parasitic diseases in which the parasite utilizes a critical cysteine protease from the papain family. Examples of parasitic diseases to be treated or prevented by the compounds of the invention include, but are not limited to, toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, coccidiosis, giardiosis, cryptosporidiosis or schistosomiasis.

  本发明涉及一种能够抑制和/或减少一种或多种半胱氨酸蛋白酶活性的化合物，从而治疗和/或预防与一种或多种半胱氨酸蛋白酶相关的各种疾病状态，包括但不限于cathepsins和木瓜蛋白酶样半胱氨酸蛋白酶。本发明的化合物治疗和/或预防的疾病状态包括但不限于寄生于哺乳动物的寄生病，其中寄生虫利用木瓜家族的关键半胱氨酸蛋白酶。本发明的化合物可用于治疗或预防的寄生病例包括但不限于弓形虫病、疟疾、非洲锥虫病、查加斯病、利什曼病、球虫病、贾第虫病、隐孢子虫病或血吸虫病。
• [EN] CATHEPSIN B INHIBITORS<br/>[FR] INHIBITEURS DE CATHEPSINE B
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2010069069A1

  公开（公告）日：2010-06-24

  Compounds of formula I, including individual diastereomers thereof and pharmaceutically acceptable salts and hydrates thereof, are selective inhibitors of cathepsin B, and are useful in treating pathological conditions that are treated by inhibiting cathepsin B.

  公式I的化合物，包括其个别的对映体和药学上可接受的盐和水合物，是选择性的cathepsin B抑制剂，可用于治疗通过抑制cathepsin B治疗的病理性状况。
• Synthesis, evaluation and molecular modeling of cyclic tetrapeptide histone deacetylase inhibitors as anticancer agents
  作者：Dawei Huang、Xiaohui Li、Lei Sun、Zhilong Xiu、Norikazu Nishino

  DOI：10.1002/psc.2392

  日期：2012.4

  Histone deacetylase inhibitors (HDACIs) are a promising class of anticancer agents. To examine whether a slight change in the recognition domain could alter their inhibitory activity, we synthesized a series of cyclo(−l‐Am7(S2Py)‐Aib‐l‐Phe(n‐Me)‐d‐Pro)derivatives and evaluated their HDAC inhibitory and anticancer activities. The peptides exhibited potent HDAC inhibitory activity and inhibited three

  组蛋白脱乙酰基酶抑制剂（HDACIs）是一类有前途的抗癌药。为了检查识别域的轻微变化是否会改变其抑制活性，我们合成了一系列环（− l‐ Am7（S2Py）‐Aib‐ l‐ Phe（n‐ Me）‐d‐ Pro）衍生物并对其进行了评估HDAC的抑制和抗癌活性。该肽表现出有效的HDAC抑制活性，并用IC 50抑制了三种人类癌细胞系在微摩尔范围内。进行了对接和分子动力学模拟，以探索I类和II类HDAC与这些抑制剂的相互作用机理。结果表明，活性部位的锌离子配位了HDACs的五个原子和抑制剂的硫原子。这些化合物的金属结合域与HDAC2相互作用，并且这些化合物的表面识别域通过氢键与HDAC4相互作用。疏水相互作用也为稳定复合物提供了有利的贡献。从这项研究中获得的结果将有助于我们设计一些可能有效的HDACI的新型环状四肽。版权所有©2012欧洲肽协会和John Wiley＆Sons，Ltd.
• CATHEPSIN CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF VARIOUS DISEASES
  申请人：Black Cameron

  公开号：US20120101053A1

  公开（公告）日：2012-04-26

  The present invention relates to compounds capable of inhibiting and/or decreasing the activity of one or more cathepsins, thereby treating and/or preventing various disease states associated with one or more cysteine proteases including, but not limited to, cathepsins and papain-like cysteine proteases. Disease states treated and/or prevented by the compounds of the invention include, but are not limited to, mammalian parasitic diseases in which the parasite utilizes a critical cysteine protease from the papain family. Examples of parasitic diseases to be treated or prevented by the compounds of the invention include, but are not limited to, toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, coccidiosis, giardiosis, cryptosporidiosis or schistosomiasis.

  本发明涉及一种能够抑制和/或减少一种或多种蛋白酶（包括但不限于cathepsins和木瓜样半胱氨酸蛋白酶）活性的化合物，从而治疗和/或预防与一种或多种半胱氨酸蛋白酶相关的各种疾病状态。本发明的化合物治疗和/或预防的疾病状态包括但不限于寄生虫病，其中寄生虫利用来自木瓜家族的关键半胱氨酸蛋白酶。本发明的化合物可用于治疗或预防的寄生虫疾病的例子包括但不限于弓形虫病、疟疾、非洲锥虫病、恙虫病、利什曼病、球虫病、贾第鞭毛虫病、隐孢子虫病或血吸虫病。