(2S,3R)-3-(BOC-氨基)-2-羟基-5-甲基己酸 | 73397-25-8

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (2S,3R)-3-(BOC-氨基)-2-羟基-5-甲基己酸
• 中文别名: Boc-(2S,3R)-3-氨基-2-羟基-5-甲基己酸
• 英文名称: (2S,3R)-3-<<(tert-Butyloxy)carbonyl>amino>-2-hydroxy-5-methylhexanoic Acid
• 英文别名: (2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-5-methylhexanoic acid；N-t-Boc-(2S,3R)-3-amino-2-hydroxy-5-methylhexanoic acid；(2S,3R)-3-{[(tert-Butyloxy)carbonyl]amino}-2-hydroxy-5-methylhexanoic Acid；(2S,3R)-2-hydroxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid
• CAS: 73397-25-8
• 化学式: C₁₂H₂₃NO₅
• mdl: MFCD00070262
• 分子量: 261.318
• InChiKey: DJZCWTDKDFJARG-BDAKNGLRSA-N

物化性质

• 沸点：
  419.7±35.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924199090

反应信息

• 作为反应物：
  描述：

  (2S,3R)-3-(BOC-氨基)-2-羟基-5-甲基己酸 在 sodium hydroxide 、 水 、 三氟乙酸 作用下， 生成 (2R,3S)-3-amino-2-hydroxy-5-methylhexanoic acid
  参考文献：
  名称：

  Synthesis of (2S,3R)-3-amino-2-hydroxy-5-methylhexanoic acid derivatives. Application to the synthesis of amastatin, an inhibitor of aminopeptidases

  摘要：

  DOI：

  10.1021/jo01300a004
• 作为产物：
  描述：

  benzyl ((1S,2S)-1-cyano-1-hydroxy-4-methylpentan-2-yl)carbamate 在 盐酸 、 sodium hydroxide 、 水 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醚 、 水 为溶剂， 反应 13.0h， 生成 (2S,3R)-3-(BOC-氨基)-2-羟基-5-甲基己酸
  参考文献：
  名称：

  Synthesis of (2S,3R)-3-amino-2-hydroxy-5-methylhexanoic acid derivatives. Application to the synthesis of amastatin, an inhibitor of aminopeptidases

  摘要：

  DOI：

  10.1021/jo01300a004

文献信息

• A two-step chemical/chiroptical method for determining absolute configurations of α-hydroxy acids
  作者：Barry H. Rickman、Stefan Matile、Koji Nakanishi、Nina Berova

  DOI：10.1016/s0040-4020(98)00221-x

  日期：1998.5

  A general, chemical/chiroptical approach based on the CD exciton chirality method has been developed to determine the absolute configuration of α-hydroxy acids. This approach consists of amidation of the carboxyl group with ethanolamine followed by derivatization with the hydrophobic 10,15,20-triphenylporphyrinyl-5-benzoyl chromophore to form π,π-bisporphyrin derivatives which undergo intramolecular

  已经开发了一种基于CD激子手性方法的常规化学/手性方法来确定α-羟基酸的绝对构型。该方法包括用乙醇胺酰胺化羧基，然后用疏水的10,15,20-三苯基卟啉基-5-苯甲酰基生色团衍生化，形成π，π-双卟啉衍生物，然后进行分子内堆积。由这种堆叠（在甲基环己烷中）产生的观察到的双键对偶的符号由优选的较低能构象体决定，并反映了立体中心的绝对构型。
• PYRIDINE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP3150581A1

  公开（公告）日：2017-04-05

  The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically a pharmaceutically composition for treating nocturia. The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-[4-(substituted pyridine)-2-yl]methyl}-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.

  本发明要解决的问题是提供一种适用于药物组合物的化合物，特别是一种用于治疗夜尿症的药物组合物。 本发明者假定，抑制胎盘亮氨酸氨肽酶（P-LAP）（即裂解 AVP 的氨肽酶）的夜间活性将维持和/或增加内源性 AVP 水平，从而增强抗利尿作用，这将有助于减少夜间排尿次数，并对抑制 P-LAP 的化合物进行了广泛研究。 结果，本发明人发现(2R)-3-氨基-2-[4-（取代的吡啶）-2-基]甲基}-2-羟基丙酸衍生物具有极佳的 P-LAP 抑制活性。本发明者评估了水负荷大鼠的抗利尿作用，发现这些化合物通过抑制 P-LAP 增加了内源性 AVP 水平，从而减少了尿量。因此，本发明提供的化合物有望用作基于 P-LAP 抑制作用的夜尿症治疗剂。
• Pyridine derivative
  申请人：Astellas Pharma Inc.

  公开号：US10059720B2

  公开（公告）日：2018-08-28

  The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically a pharmaceutically composition for treating nocturia. The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-[4-(substituted pyridine)-2-yl]methyl}-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.

  本发明要解决的问题是提供一种适用于药物组合物的化合物，特别是一种用于治疗夜尿症的药物组合物。 本发明者假定，抑制胎盘亮氨酸氨肽酶（P-LAP）（即能裂解 AVP 的氨肽酶）的夜间活性将维持和/或增加内源性 AVP 水平，从而增强抗利尿作用，这将有助于减少夜间排尿次数，并对抑制 P-LAP 的化合物进行了广泛研究。 结果，本发明人发现(2R)-3-氨基-2-[4-（取代的吡啶）-2-基]甲基}-2-羟基丙酸衍生物具有极佳的 P-LAP 抑制活性。本发明者评估了水负荷大鼠的抗利尿作用，发现这些化合物通过抑制 P-LAP 增加了内源性 AVP 水平，从而减少了尿量。因此，本发明提供的化合物有望用作基于 P-LAP 抑制作用的夜尿症治疗剂。
• Synthesis of New (−)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase
  作者：Geetha Velmourougane、Michael B. Harbut、Seema Dalal、Sheena McGowan、Christine A. Oellig、Nataline Meinhardt、James C. Whisstock、Michael Klemba、Doron C. Greenbaum

  DOI：10.1021/jm101227t

  日期：2011.3.24

  The malarial PfA-M1 metalloaminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-D-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural a-amino add (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBz1) 16 at the 131 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PEA-M1 pocket that interacts with the PI side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.
• TW2016/9654
  申请人：——

  公开号：——

  公开（公告）日：——