3-(Dimethylamino)oximinomethyl-4-aminofurazan | 129206-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 亚胺内酰胺
• 英文名称: 3-(Dimethylamino)oximinomethyl-4-aminofurazan
• 英文别名: 4-amino-N'-hydroxy-N,N-dimethyl-1,2,5-oxadiazole-3-carboximidamide
• CAS: 129206-45-7
• 化学式: C₅H₉N₅O₂
• 分子量: 171.159
• InChiKey: CEOCAUMQZJIHCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(Dimethylamino)oximinomethyl-4-aminofurazan 在 盐酸 、 三乙胺 、 sodium chloride 、 potassium hydroxide 、 sodium nitrite 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 15.0h， 生成 N-(3-bromo-4-fluorophenyl)-4-(dimethylamino)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide
  参考文献：
  名称：

  INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology

  摘要：

  A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 41, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested. The extensive intramolecular hydrogen bonding observed in the small molecule crystal structure of 4f is believed to significantly contribute to the observed permeability and PK Epacadostat in combination with anti-PD1 mAb pembrolizumab is currently being studied in a phase 3 clinical trial in patients with unresectable or metastatic melanoma.

  DOI：

  10.1021/acsmedchemlett.6b00391
• 作为产物：
  描述：

  二甲胺 、 4-氨基-1,2,5-恶二唑-3-氯化甲醛肟 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 3-(Dimethylamino)oximinomethyl-4-aminofurazan
  参考文献：
  名称：

  INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology

  摘要：

  A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 41, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested. The extensive intramolecular hydrogen bonding observed in the small molecule crystal structure of 4f is believed to significantly contribute to the observed permeability and PK Epacadostat in combination with anti-PD1 mAb pembrolizumab is currently being studied in a phase 3 clinical trial in patients with unresectable or metastatic melanoma.

  DOI：

  10.1021/acsmedchemlett.6b00391

文献信息

• New synthesis of 1,2,4-oxadiazoles
  作者：V.N. Yarovenko、V.K. Taralashvili、I.V. Zavarzin、M.M. Krayushkin

  DOI：10.1016/s0040-4020(01)90529-0

  日期：1990.1
• INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology
  作者：Eddy W. Yue、Richard Sparks、Padmaja Polam、Dilip Modi、Brent Douty、Brian Wayland、Brian Glass、Amy Takvorian、Joseph Glenn、Wenyu Zhu、Michael Bower、Xiangdong Liu、Lynn Leffet、Qian Wang、Kevin J. Bowman、Michael J. Hansbury、Min Wei、Yanlong Li、Richard Wynn、Timothy C. Burn、Holly K. Koblish、Jordan S. Fridman、Tom Emm、Peggy A. Scherle、Brian Metcalf、Andrew P. Combs

  DOI：10.1021/acsmedchemlett.6b00391

  日期：2017.5.11

  A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 41, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested. The extensive intramolecular hydrogen bonding observed in the small molecule crystal structure of 4f is believed to significantly contribute to the observed permeability and PK Epacadostat in combination with anti-PD1 mAb pembrolizumab is currently being studied in a phase 3 clinical trial in patients with unresectable or metastatic melanoma.