4-(3-bromo-4-fluorophenyl)-3-[4-(methylamino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5-(4H)-one | 914471-61-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-bromo-4-fluorophenyl)-3-[4-(methylamino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5-(4H)-one
• 英文别名: 4-(3-Bromo-4-fluorophenyl)-3-[4-(methylamino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5(4H)-one；4-(3-bromo-4-fluorophenyl)-3-[4-(methylamino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5-one
• CAS: 914471-61-7
• 化学式: C₁₁H₇BrFN₅O₃
• 分子量: 356.111
• InChiKey: BKVATGJGVDRJSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  92.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(3-bromo-4-fluorophenyl)-3-[4-(methylamino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5-(4H)-one 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 以70%的产率得到N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-(methylamino)-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：

  3-(4-氨基-1,2,5-恶二唑-3-基)-4-(3-溴-4-氟苯基)-1,2,4-恶二唑-5(4H)-酮 在 吡啶 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-(3-bromo-4-fluorophenyl)-3-[4-(methylamino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5-(4H)-one
  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

• Modulators of indoleamine 2,3-dioxygenase and methods of using the same
  申请人：Combs P. Andrew

  公开号：US20060258719A1

  公开（公告）日：2006-11-16

  The present invention is directed to modulators of indoleamine 2,3-dioxygenase (IDO), as well as compositions and pharmaceutical methods thereof.

  本发明涉及色氨酸2,3-二氧化酶（IDO）的调节剂，以及其组合物和药用方法。
• MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF USING THE SAME
  申请人：Combs Andrew P.

  公开号：US20110311479A1

  公开（公告）日：2011-12-22

  The present invention is directed to modulators of indoleamine 2,3-dioxygenase (IDO), as well as compositions and pharmaceutical methods thereof.

  本发明涉及吲哚胺2,3-二氧化酶(IDO)的调节剂，以及其组成物和制药方法。
• Modulators of indoleamine 2,3-dioxygenase and methods of using the same for treating cancer
  申请人：Combs Andrew P.

  公开号：US08372870B2

  公开（公告）日：2013-02-12

  The present invention is directed to modulators of indoleamine 2,3-dioxygenase (IDO), as well as compositions and pharmaceutical methods thereof.

  本发明涉及吲哚胺2,3-二氧化酶(IDO)的调节剂，以及其组成物和制药方法。
• EP1879573A4
  申请人：——

  公开号：EP1879573A4

  公开（公告）日：2009-07-08
• US8034953B2
  申请人：——

  公开号：US8034953B2

  公开（公告）日：2011-10-11