(Z)-4-(pyridin-3-ylmethylene)-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: (Z)-4-(pyridin-3-ylmethylene)-2-[(E)-styryl]oxazol-5(4H)-one
• 英文别名: 2-(2-Phenylethenyl)-4-(pyridin-3-ylmethylidene)-4,5-dihydro-1,3-oxazol-5-one；(4Z)-2-[(E)-2-phenylethenyl]-4-(pyridin-3-ylmethylidene)-1,3-oxazol-5-one
• 化学式: C₁₇H₁₂N₂O₂
• 分子量: 276.294
• InChiKey: GFGMISOSPOPSHN-NOCYUORASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  正丙胺 、 (Z)-4-(pyridin-3-ylmethylene)-2-[(E)-styryl]oxazol-5(4H)-one 以 乙醇 为溶剂， 反应 2.0h， 以74%的产率得到(Z)-2-cinnamamido-N-propyl-3-(pyridin-3-yl)acrylamide
  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：

  3-吡啶甲醛 、 肉桂酰甘氨酸 在 乙酸酐 作用下， 生成 (Z)-4-(pyridin-3-ylmethylene)-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

• INHIBITOR OF CASEIN KINASE 1DELTA AND CASEIN KINASE 1EPSILON
  申请人：Okamoto Masako

  公开号：US20110294857A1

  公开（公告）日：2011-12-01

  There is provided an inhibitor that inhibits casein kinase 1δ and casein kinase 1ε, and thus, there is also provided a pharmaceutical agent useful for the treatment and/or prevention of a disease, with the pathological condition of which the mechanism of activation of casein kinase 1δ or casein kinase 1ε is associated. Particularly, the above-described inhibitor is used to provide a pharmaceutical agent useful for the treatment of circadian rhythm disorder (including sleep disorder), central neurodegenerative disease, and cancer. An inhibitor of casein kinase 1δ and casein kinase 1ε, which comprises, as an active ingredient, an oxazolone derivative represented by the following general formula (1), a salt thereof, a solvate thereof, or a hydrate thereof: [wherein, in the formula (1), each of R 1 and R 2 independently represents any one of a substituted or unsubstituted 6-membered or 5-membered heterocyclic group optionally having a condensed ring, a substituted or unsubstituted aromatic hydrocarbon group optionally having a condensed ring, and a substituted or unsubstituted aromatic hydrocarbon lower alkyl group or aromatic hydrocarbon lower alkenyl group optionally having a condensed ring.]

  提供了一种抑制剂，可抑制酪蛋白激酶1δ和酪蛋白激酶1ε，因此还提供了一种用于治疗和/或预防疾病的药物，该疾病的病理条件与酪蛋白激酶1δ或酪蛋白激酶1ε的激活机制相关。特别地，上述描述的抑制剂用于提供一种用于治疗昼夜节律紊乱（包括睡眠障碍）、中枢神经退行性疾病和癌症的药物。一种酪蛋白激酶1δ和酪蛋白激酶1ε的抑制剂，包括以下一般式（1）所表示的噁唑酮衍生物作为活性成分，其盐、溶剂化合物或水合物：[在式（1）中，R1和R2中的每一个独立地表示取代或未取代的6元或5元杂环基，可选择具有缩合环的取代或未取代的芳香烃基，以及取代或未取代的芳香烃基低烷基基团或芳香烃基低烯基基团，可选择具有缩合环。]
• 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。
• Culture medium and method for inducing differentiation of pluripotent stem cells to hepatoblasts
  申请人：National University Corporation Chiba University

  公开号：US10006005B2

  公开（公告）日：2018-06-26

  Provided are a method of inducing differentiation of pluripotent stem cells, such as induced pluripotent stem cells (hereinafter abbreviated as iPS cells), to hepatocytes in a short period of time, and a substance to be used in the method. Specifically, provided are a method of producing a cell culture formed substantially of hepatoblasts, the method including culturing pluripotent stem cells, such as iPS cells, in a culture medium having a composition shown in Table 1 below, and a culture medium for inducing differentiation of pluripotent stem cells into hepatoblasts, which has a composition shown in Table 1 below.

  本发明提供了一种在短时间内诱导多能干细胞（如诱导多能干细胞，以下简称iPS细胞）分化为肝细胞的方法，以及一种用于该方法的物质。具体地说，提供了一种生产基本上由肝母细胞形成的细胞培养物的方法，该方法包括在具有下表1所示成分的培养基中培养多能干细胞，例如iPS细胞，以及一种用于诱导多能干细胞分化成肝母细胞的培养基，该培养基具有下表1所示的成分。
• 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。