N-(tert-butoxycarbonyl)-D-γ-glutamyl-D-tryptophan | 186087-52-5

• 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-(tert-butoxycarbonyl)-D-γ-glutamyl-D-tryptophan
• 英文别名: Boc-D-Glu(D-Trp-OH)-OH；(2R)-5-[[(1R)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid
• CAS: 186087-52-5
• 化学式: C₂₁H₂₇N₃O₇
• 分子量: 433.461
• InChiKey: SOCSCSDEUCMLEB-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  158
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)-D-γ-glutamyl-D-tryptophan 在 盐酸 、 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.58h， 生成 H-D-Glu(D-Trp-OCH₂CF₃)-OCH₂CF₃ hydrochloride
  参考文献：
  名称：

  [EN] PRODRUGS OF D-ISOGLUTAMYL-[D/L]-TRYPTOPHAN
  [FR] PROMÉDICAMENTS DE D-ISOGLUTAMYL-[D/L]-TRYPTOPHANE

  摘要：

  提供了公式（I）的羧酸酯衍生物，其制备方法以及使用方法。这些化合物是D-异谷氨酰-[D/L]-色氨酸的前药。对一些前药在人类肝细胞和人类血液中转化为母药D-异谷氨酰-D-色氨酸（或胸腺抑制素）的体外生物转化进行了测试。还报告了将一些前药口服给大鼠后的体内药代动力学研究。

  公开号：

  WO2012129671A1

文献信息

• [EN] PRODRUGS OF D-GAMMA-GLUTAMYL-D-TRYPTOPHAN AND D-GAMMA- GLUTAMYL-L-TRYPTOPHAN<br/>[FR] PROMÉDICAMENTS DE D-GAMMA-GLUTAMYL-D-TRYPTOPHANE ET D-GAMMA-GLUTAMYL-L-TRYPTOPHANE
  申请人：APOTEX TECHNOLOGIES INC

  公开号：WO2012129680A1

  公开（公告）日：2012-10-04

  The present invention provides pro-drugs of D-gamma-glutamyl-[D/L] -tryptophan, said pro-drugs are compounds of Formula I or pharmaceutically acceptable salts thereof, wherein G is C1-C8 alkyl or benzyl, T is C1-C8 alkyl or benzyl, and * is a chiral carbon in a (R) or (S) configuration, provided that when * is in the (R) configuration, at least one of G and T is C5-C8 alkyl; and use of compounds of Formula I in a pharmaceutical composition.

  本发明提供D-γ-谷氨酰-[D/L]-色氨酸的前药，所述前药是化合物I的药用可接受盐，其中G为C1-C8烷基或苄基，T为C1-C8烷基或苄基，*为(R)或(S)构型的手性碳，但当*为(R)构型时，至少有一个G和T为C5-C8烷基；以及化合物I在制药组合物中的使用。
• CRYSTALLINE D-ISOGLUTAMYL-D-TRYPTOPHAN AND THE MONO AMMONIUM SALT OF D-ISOGLUTAMYL-D-TRYPTOPHAN
  申请人：Tam Tim Fat

  公开号：US20100016243A1

  公开（公告）日：2010-01-21

  A process for making pure crystalline D-isoglutamyl-D-tryptophan is provided which includes the step of deprotecting essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan or its diester to yield essentially pure D-isoglutamyl-D-tryptophan. A process is also provided for the preparation of pure mono ammonium salt of D-isoglutamyl-D-tryptophan from essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan. D-isoglutamyl-D-tryptophan, ammonium salt (1:1) is a stable pharmaceutical solid.

  提供了一种制备纯结晶D-异戊氨酰-D-色氨酸的过程，包括去保护基本纯的N-叔丁氧羰基-D-异戊氨酰-D-色氨酸或其二酯的步骤，以得到基本纯的D-异戊氨酰-D-色氨酸。还提供了一种从基本纯的N-叔丁氧羰基-D-异戊氨酰-D-色氨酸制备纯D-异戊氨酰-D-色氨酸单铵盐的过程。D-异戊氨酰-D-色氨酸，铵盐（1:1）是一种稳定的药用固体。
• ORALLY BIOAVAILABLE D-GAMMA-GLUTAMYL-D-TRYPTOPHAN
  申请人：TAM Tim Fat

  公开号：US20120157387A1

  公开（公告）日：2012-06-21

  Provided are compounds which are prodrugs of D-gamma-glutamyl-D-tryptophan, methods of making the compounds and methods for using the compounds.

  提供的是D-γ-谷氨酰-D-色氨酸的前药化合物，制备这些化合物的方法以及使用这些化合物的方法。
• CRYSTALLINE D-ISOGLUTAMYL-D-TRYPTOPHAN AND THE MONO AMMONIUM SLAT OF D-ISOGLUTAMYL-D-TRYPTOPHAN
  申请人：TAM Tim Fat

  公开号：US20130059791A1

  公开（公告）日：2013-03-07

  A process for making pure crystalline D-isoglutamyl-D-tryptophan is provided which includes the step of deprotecting essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan or its diester to yield essentially pure D-isoglutamyl-D-tryptophan. A process is also provided for the preparation of pure mono ammonium salt of D-isoglutamyl-D-tryptophan from essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan. D-isoglutamyl-D-tryptophan, ammonium salt (1:1) is a stable pharmaceutical solid.

  提供了一种制备纯结晶D-异谷氨酰-D-色氨酸的过程，包括去保护基的步骤，将基本上纯的N-叔丁氧羰基-D-异谷氨酰-D-色氨酸或其二酯去保护，得到基本上纯的D-异谷氨酰-D-色氨酸。还提供了一种从基本上纯的N-叔丁氧羰基-D-异谷氨酰-D-色氨酸制备纯D-异谷氨酰-D-色氨酸单酰胺盐的过程。D-异谷氨酰-D-色氨酸铵盐（1:1）是一种稳定的药物固体。
• PRODRUGS OF D-GAMMA-GLUTAMYL-D-TRYPTOPHAN AND D-GAMMA-GLUTAMYL-L-TRYPTOPHAN
  申请人：APOTEX TECHNOLOGIES, INC.

  公开号：US20150011484A1

  公开（公告）日：2015-01-08

  The present invention provides pro-drugs of D-gamma-glutamyl-[D/L]-tryptophan, said pro-drugs are compounds of Formula I or pharmaceutically acceptable salts thereof, wherein G is C 1 -C 8 alkyl or benzyl, T is C 1 -C 8 alkyl or benzyl, and * is a chiral carbon in a (R) or (S) configuration, provided that when * is in the (R) configuration, at least one of G and T is C 5 -C 8 alkyl; and use of compounds of Formula I in a pharmaceutical composition.

  本发明提供D-γ-谷氨酰-[D/L]-色氨酸的前药，所述前药是公式I的化合物或其药学上可接受的盐，其中G是C1-C8烷基或苄基，T是C1-C8烷基或苄基，而*是具有(R)或(S)构型的手性碳，前提是当*处于(R)构型时，G和T中至少有一个是C5-C8烷基；以及公式I化合物在制药组合物中的用途。