benzyl N^α-(tert-butoxycarbonyl)-1-methyl-D-tryptophanate | 862403-33-6

• 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: benzyl N^α-(tert-butoxycarbonyl)-1-methyl-D-tryptophanate
• 英文别名: (R)-2-t-butoxycarbonylamino-3-(1-methyl-1H-indol-3-yl)propionic acid benzyl ester；benzyl (2R)-3-(1-methylindol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 862403-33-6
• 化学式: C₂₄H₂₈N₂O₄
• 分子量: 408.497
• InChiKey: NCFSRPHQTQLCAK-HXUWFJFHSA-N

物化性质

• 沸点：
  585.3±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl N^α-(tert-butoxycarbonyl)-1-methyl-D-tryptophanate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 2.75h， 以88%的产率得到benzyl 1-methyl-D-tryptophanate hydrochloride
  参考文献：
  名称：

  SALTS AND PRODRUGS OF 1-METHYL-D-TRYPTOPHAN

  摘要：

  目前提供的是吲哚氧化酶抑制剂前药和盐类化合物，以及包含吲哚氧化酶抑制剂前药和盐类的药物组合物，相比直接给予吲哚氧化酶抑制剂，这些组合物在需要治疗由吲哚胺-2,3-二氧化酶途径介导的免疫抑制的患者中，如癌症或慢性传染病患者，能够产生增强的血浆浓度和暴露于吲哚氧化酶抑制剂。

  公开号：

  US20170022157A1
• 作为产物：
  描述：

  1-甲基-D-色氨酸 在 caesium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl N^α-(tert-butoxycarbonyl)-1-methyl-D-tryptophanate
  参考文献：
  名称：

  SALTS AND PRODRUGS OF 1-METHYL-D-TRYPTOPHAN

  摘要：

  目前提供的是吲哚氧化酶抑制剂前药和盐类化合物，以及包含吲哚氧化酶抑制剂前药和盐类的药物组合物，相比直接给予吲哚氧化酶抑制剂，这些组合物在需要治疗由吲哚胺-2,3-二氧化酶途径介导的免疫抑制的患者中，如癌症或慢性传染病患者，能够产生增强的血浆浓度和暴露于吲哚氧化酶抑制剂。

  公开号：

  US20170022157A1

文献信息

• Hydroxamic Acid Derivative And Age Generation Inhibitor Containing The Derivative
  申请人：Kakuchi Junji

  公开号：US20080132539A1

  公开（公告）日：2008-06-05

  To provide a novel compound which inhibits the generation of AGE and an AGE generation inhibitor containing the compound. A compound represented by the following formula or a pharmaceutically acceptable salt thereof, a medicinal composition containing the compound or such a salt thereof, and an additive composition containing the compound.

  提供一种新化合物，可抑制AGE的生成，并含有该化合物的AGE生成抑制剂。该化合物由以下公式表示或其药学上可接受的盐，药物组合物包含该化合物或其盐，以及含有该化合物的添加剂组合物。
• HYDROXAMIC ACID DERIVATIVE AND AGE GENERATION INHIBITOR CONTAINING THE DERIVATIVE
  申请人：Kureha Corporation

  公开号：EP1707560A1

  公开（公告）日：2006-10-04

  To provide a novel compound which inhibits the generation of AGE and an AGE generation inhibitor containing the compound. A compound represented by the following formula or a pharmaceutically acceptable salt thereof, a medicinal composition containing the compound or such a salt thereof, and an additive composition containing the compound.

  提供一种抑制 AGE 生成的新型化合物和一种含有该化合物的 AGE 生成抑制剂。一种由下式代表的化合物或其药学上可接受的盐、一种含有该化合物或其盐的药物组合物，以及一种含有该化合物的添加剂组合物。
• Salts and prodrugs of 1-methyl-D-tryptophan
  申请人：NewLink Genetics, Corp.

  公开号：US10207990B2

  公开（公告）日：2019-02-19

  Presently provided are indoximod prodrug and salt compounds and pharmaceutical compositions comprising salts and prodrugs of indoximod, that produce enhanced plasma concentration and exposure to indoximod compared to direct administration of indoximod, in patients in need of treatment of immunosuppression mediated by the indoleamine-2,3-dioxygenase pathway, such as patients with cancer or chronic infectious diseases.

  目前提供的吲哚西莫德原药和盐类化合物以及包含吲哚西莫德盐类和原药的药物组合物，与直接服用吲哚西莫德相比，可提高需要治疗由吲哚胺-2,3-二氧酶途径介导的免疫抑制的患者（如癌症或慢性传染病患者）的血浆浓度和吲哚西莫德暴露量。
• Discovery of indoximod prodrugs and characterization of clinical candidate NLG802
  作者：Sanjeev Kumar、Firoz A. Jaipuri、Jesse P. Waldo、Hima Potturi、Agnieszka Marcinowicz、James Adams、Clarissa Van Allen、Hong Zhuang、Nicholas Vahanian、Charles Link、Erik L. Brincks、Mario R. Mautino

  DOI：10.1016/j.ejmech.2020.112373

  日期：2020.7

  A series of different prodrugs of indoximod, including estesrs and peptide amides were synthesized with the aim of improving its oral bioavailability in humans. The pharmacokinetics of prodrugs that were stable in buffers, plasma and simulated gastric and intestinal fluids was first assessed in rats after oral dosing in solution or in capsule formulation. Two prodrugs that produced the highest exposure to indoximod in rats were further tested in Cynomolgus monkeys, a species in which indoximod has oral bioavailability of 6-10% and an equivalent dose-dependent exposure profile as humans. NLG802 was selected as the clinical development candidate after increasing oral bioavailability (>5-fold), C-max (6.1 -3.6 fold) and AUC (2.9-5.2 fold) in monkeys, compared to equivalent molar oral doses of indoximod. NLG802 is extensively absorbed and rapidly metabolized to indoximod in all species tested and shows a safe toxicological profile at the anti-cipated therapeutic doses. NLG802 markedly enhanced the anti-tumor responses of tumor-specific pmel-1 T cells in a melanoma tumor model. In conclusion, NLG802 is a prodrug of indoximod expected to increase clinical drug exposure to indoximod above the current achievable levels, thus increasing the possibility of therapeutic effects in a larger fraction of the target patient population. (C) 2020 The Authors. Published by Elsevier Masson SAS.
• EP1707560
  申请人：——

  公开号：——

  公开（公告）日：——