4-[(Z)-4-(dimethylamino)benzylidene]-2-[(E)-styryl]oxazol-5(4H)-one

• 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: 4-[(Z)-4-(dimethylamino)benzylidene]-2-[(E)-styryl]oxazol-5(4H)-one
• 英文别名: (4Z)-4-[[4-(dimethylamino)phenyl]methylidene]-2-[(E)-2-phenylethenyl]-1,3-oxazol-5-one
• 化学式: C₂₀H₁₈N₂O₂
• 分子量: 318.375
• InChiKey: OFYWCLPPONVQKJ-LQZBDKQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  正丙胺 、 4-[(Z)-4-(dimethylamino)benzylidene]-2-[(E)-styryl]oxazol-5(4H)-one 以 乙醇 为溶剂， 反应 2.0h， 以87%的产率得到(Z)-2-cinnamamido-3-[4-(dimethylamino)phenyl]-N-propylacrylamide
  参考文献：
  名称：

  Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress

  摘要：

  Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 mu M), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido) propenamide] 45 killed colon cancer cells at IC50 = 0.89 mu M (Caco-2), 2.85 mu M (HCT-116) and 1.65 mu M (HT -29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 mu M and 77.6 mu M, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with prominent selectivity profile over non-cancerous cell lines.

  DOI：

  10.1016/j.bioorg.2020.103953
• 作为产物：
  描述：

  肉桂酰甘氨酸 、 对二甲氨基苯甲醛 在 乙酸酐 作用下， 生成 4-[(Z)-4-(dimethylamino)benzylidene]-2-[(E)-styryl]oxazol-5(4H)-one
  参考文献：
  名称：

  Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress

  摘要：

  Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 mu M), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido) propenamide] 45 killed colon cancer cells at IC50 = 0.89 mu M (Caco-2), 2.85 mu M (HCT-116) and 1.65 mu M (HT -29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 mu M and 77.6 mu M, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with prominent selectivity profile over non-cancerous cell lines.

  DOI：

  10.1016/j.bioorg.2020.103953

文献信息

• Pharmaceutical composition with cytotoxic activity on colorectal cancer cells
  申请人：King Abdulaziz University

  公开号：US10836736B1

  公开（公告）日：2020-11-17

  A compound of formula (I), wherein R1 is an optionally substituted aryl or an optionally substituted heteroaryl, R2 is an optionally substituted aryl or an optionally substituted heteroaryl, and R3 is an optionally substituted alkylamino, an optionally substituted cycloalkylamino, an optionally substituted arylamino, an optionally substituted heterocyclylamino, an optionally substituted heterocyclyl, and an optionally substituted dialkylamino. A pharmaceutical composition which includes the compound of formula (I) and a pharmaceutically acceptable carrier and/or excipient. A method of treating colorectal cancer in a subject, whereby a therapeutically effective amount of the compound of formula (I) is administered to the subject.

  化合物的化学式为（I），其中R1是可选取代的芳基或可选取代的杂环基，R2是可选取代的芳基或可选取代的杂环基，R3是可选取代的烷基氨基，可选取代的环烷基氨基，可选取代的芳基氨基，可选取代的杂环基氨基，可选取代的杂环基和可选取代的二烷基氨基。一种制备方法包括化合物（I）和药学上可接受的载体和/或赋形剂的制药组合物。一种治疗结直肠癌的方法，通过向患者施用化合物（I）的治疗有效量。
• Bis-propenamide compounds and methods of treating cancer
  申请人：King Abdulaziz University

  公开号：US11155528B2

  公开（公告）日：2021-10-26

  A compound of formula (I), wherein R1 is an optionally substituted aryl or an optionally substituted heteroaryl, R2 is an optionally substituted aryl or an optionally substituted heteroaryl, and R3 is an optionally substituted alkylamino, an optionally substituted cycloalkylamino, an optionally substituted arylamino, an optionally substituted heterocyclylamino, an optionally substituted heterocyclyl, and an optionally substituted dialkylamino. A pharmaceutical composition which includes the compound of formula (I) and a pharmaceutically acceptable carrier and/or excipient. A method of treating colorectal cancer in a subject, whereby a therapeutically effective amount of the compound of formula (I) is administered to the subject.

  式 (I) 的化合物、 其中 R1 是任选取代的芳基或任选取代的杂芳基，R2 是任选取代的芳基或任选取代的杂芳基，R3 是任选取代的烷基氨基、任选取代的环烷基氨基、任选取代的芳基氨基、任选取代的杂环基氨基、任选取代的杂环基和任选取代的二烷基氨基。一种药物组合物，它包括式（I）化合物和一种药学上可接受的载体和/或赋形剂。一种治疗受试者结直肠癌的方法，其中向受试者施用治疗有效量的式(I)化合物。
• Method of treating colorectal cancer
  申请人：King Abdulaziz University

  公开号：US11214556B1

  公开（公告）日：2022-01-04

  A compound of formula (I), wherein R1 is an optionally substituted aryl or an optionally substituted heteroaryl, R2 is an optionally substituted aryl or an optionally substituted heteroaryl, and R3 is an optionally substituted alkylamino, an optionally substituted cycloalkylamino, an optionally substituted arylamino, an optionally substituted heterocyclylamino, an optionally substituted heterocyclyl, and an optionally substituted dialkylamino. A pharmaceutical composition which includes the compound of formula (I) and a pharmaceutically acceptable carrier and/or excipient. A method of treating colorectal cancer in a subject, whereby a therapeutically effective amount of the compound of formula (I) is administered to the subject.

  式 (I) 的化合物、 其中 R1 是任选取代的芳基或任选取代的杂芳基，R2 是任选取代的芳基或任选取代的杂芳基，R3 是任选取代的烷基氨基、任选取代的环烷基氨基、任选取代的芳基氨基、任选取代的杂环基氨基、任选取代的杂环基和任选取代的二烷基氨基。一种药物组合物，它包括式（I）化合物和一种药学上可接受的载体和/或赋形剂。一种治疗受试者结直肠癌的方法，其中向受试者施用治疗有效量的式(I)化合物。
• Method for making propenamide compound
  申请人：King Abdulaziz University

  公开号：US11312694B2

  公开（公告）日：2022-04-26

  A compound of formula (I), wherein R1 is an optionally substituted aryl or an optionally substituted heteroaryl, R2 is an optionally substituted aryl or an optionally substituted heteroaryl, and R3 is an optionally substituted alkylamino, an optionally substituted cycloalkylamino, an optionally substituted arylamino, an optionally substituted heterocyclylamino, an optionally substituted heterocyclyl, and an optionally substituted dialkylamino. A pharmaceutical composition which includes the compound of formula (I) and a pharmaceutically acceptable carrier and/or excipient. A method of treating colorectal cancer in a subject, whereby a therapeutically effective amount of the compound of formula (I) is administered to the subject.

  式 (I) 的化合物、 其中 R1 是任选取代的芳基或任选取代的杂芳基，R2 是任选取代的芳基或任选取代的杂芳基，R3 是任选取代的烷基氨基、任选取代的环烷基氨基、任选取代的芳基氨基、任选取代的杂环基氨基、任选取代的杂环基和任选取代的二烷基氨基。一种药物组合物，它包括式（I）化合物和一种药学上可接受的载体和/或赋形剂。一种治疗受试者结直肠癌的方法，其中向受试者施用治疗有效量的式(I)化合物。
• BIS-PROPENAMIDE COMPOUNDS AND METHODS OF TREATING CANCER
  申请人：King Abdulaziz University

  公开号：US20210122721A1

  公开（公告）日：2021-04-29

  A compound of formula (I), wherein R 1 is an optionally substituted aryl or an optionally substituted heteroaryl, R 2 is an optionally substituted aryl or an optionally substituted heteroaryl, and R 3 is an optionally substituted alkylamino, an optionally substituted cycloalkylamino, an optionally substituted arylamino, an optionally substituted heterocyclylamino, an optionally substituted heterocyclyl, and an optionally substituted dialkylamino. A pharmaceutical composition which includes the compound of formula (I) and a pharmaceutically acceptable carrier and/or excipient. A method of treating colorectal cancer in a subject, whereby a therapeutically effective amount of the compound of formula (I) is administered to the subject.