2-[5-(3-Methoxypropyl)-1,1-dioxo-1,2,5-thiadiazolidin-2-yl]ethanamine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫酸及其衍生物
• 英文名称: 2-[5-(3-Methoxypropyl)-1,1-dioxo-1,2,5-thiadiazolidin-2-yl]ethanamine
• 英文别名: 2-[5-(3-methoxypropyl)-1,1-dioxo-1,2,5-thiadiazolidin-2-yl]ethanamine
• 化学式: C₈H₁₉N₃O₃S
• 分子量: 237.323
• InChiKey: MPIKXXOMQRAFEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-bromo-4-fluorophenyl)-3-(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,4-oxadiazol-5(4H)-one 、 2-[5-(3-Methoxypropyl)-1,1-dioxo-1,2,5-thiadiazolidin-2-yl]ethanamine 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 N-(3-bromo-4-fluorophenyl)-N′-hydroxy-4-((2-(5-(3-methoxypropyl)-1,1-dioxido-1,2,5-thiadiazolidin-2-yl)ethyl)amino)-1,2,5-oxadiazole-3-carboximidamide
  参考文献：
  名称：

  Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors

  摘要：

  Indoleamine 2, 3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism which is an important mechanism in immune tolerance. The small molecule epacadostat is the most advanced IDO1 inhibitor, but its phase III trials as a single agent or in combinations with PD-1 antibody failed to show appreciable objective responses. To gain more insight on the antitumor efficacy of IDO1 inhibitors, we have designed a series of analogues of epacadostat by incorporating a cyclic aminosulfonamide moiety as the sidechain capping functionality. Compound 5a was found to display significant potency against recombinant hIDO1 and hIDO1 expressed HEK293 cancer cells. This compound has improved physico-chemical properties, acceptable PK parameters as well as optimal cardiac safety. Similar to epacadostat, 5a is ineffective as single agent in the CT-26 syngeneic xenograft model, however, the combination of 5a with PD-1 antibody showed both elevated tumor growth inhibition and prolonged median life span. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.037
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 2-[5-(3-Methoxypropyl)-1,1-dioxo-1,2,5-thiadiazolidin-2-yl]ethanamine
  参考文献：
  名称：

  Design, synthesis and antitumor study of a series of N-Cyclic sulfamoylaminoethyl substituted 1,2,5-oxadiazol-3-amines as new indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors

  摘要：

  Indoleamine 2, 3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism which is an important mechanism in immune tolerance. The small molecule epacadostat is the most advanced IDO1 inhibitor, but its phase III trials as a single agent or in combinations with PD-1 antibody failed to show appreciable objective responses. To gain more insight on the antitumor efficacy of IDO1 inhibitors, we have designed a series of analogues of epacadostat by incorporating a cyclic aminosulfonamide moiety as the sidechain capping functionality. Compound 5a was found to display significant potency against recombinant hIDO1 and hIDO1 expressed HEK293 cancer cells. This compound has improved physico-chemical properties, acceptable PK parameters as well as optimal cardiac safety. Similar to epacadostat, 5a is ineffective as single agent in the CT-26 syngeneic xenograft model, however, the combination of 5a with PD-1 antibody showed both elevated tumor growth inhibition and prolonged median life span. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.06.037