methyl (2Z,4E)-2-methylthio-4-nitro-5-pyrrolidino-2,4-pentadienoate | 389838-08-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (2Z,4E)-2-methylthio-4-nitro-5-pyrrolidino-2,4-pentadienoate
• 英文别名: methyl (2Z,4E)-2-methylsulfanyl-4-nitro-5-pyrrolidin-1-ylpenta-2,4-dienoate
• CAS: 389838-08-8
• 化学式: C₁₁H₁₆N₂O₄S
• 分子量: 272.325
• InChiKey: BOEFYGWXKKEFIL-AZRUORMVSA-N

物化性质

• 沸点：
  365.0±42.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-萘基溴化镁, 0.5M IN METHF 、 methyl (2Z,4E)-2-methylthio-4-nitro-5-pyrrolidino-2,4-pentadienoate 以 四氢呋喃 为溶剂， 反应 0.75h， 以78%的产率得到Methyl (2z,4e)-2-methylsulphanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate
  参考文献：
  名称：

  Design, synthesis, and in vitro evaluation of new naphthylnitrobutadienes with potential antiproliferative activity: Toward a structure/activity correlation

  摘要：

  On the grounds of previous encouraging results on the antitumor activity of (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1, 3-butadiene (1), we have designed and synthesized two new molecules [(1E,3E)-1,4-bis(4-carboxy-1-naphthyl)-2,3-dinitro-1,3-butadiene (2) and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (3)] characterized by a common naphthyl-nitrobutadiene array but with different structural properties, with the aim of approaching to some structure-activity correlation. When 2 and 3 were analyzed in vitro for their inhibition of cell proliferation and pro-apoptotic properties, the carboxyderivative 2 did not furnish appreciable results. In contrast, 3 (which contains only one of the two naphthyinitroethenyl moieties of the original compound 1) showed remarkable activities in the range of micromolar concentrations (in six over eight cell lines its IC(50)s are in the 1-3 mu M range), with a significant improvement compared to 1. In particular, 3 proved able to bind to DNA, to upregulate p53, to block cells in the G2/M phase of their cycle, and to induce apoptosis. Thus, very interestingly, the performance of 3 with respect to 1 shows that a single 1-(1-naphthyl)-2-nitroethene moiety is able to ensure better (on four out of eight of the cell lines tested) or comparable levels of activity. This result suggests that the 'molecular-simplification strategy' could furnish a useful instrument for future design in our antitumor research. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.09.042
• 作为产物：
  描述：

  四氢吡咯 、 甲基4-硝基-2-噻吩羧酸酯 、 碘甲烷 在 silver nitrate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以48%的产率得到methyl (2Z,4E)-2-methylthio-4-nitro-5-pyrrolidino-2,4-pentadienoate
  参考文献：
  名称：

  Ring opening of 2-substituted 4-nitrothiophenes with pyrrolidine. Access to new functionalized nitro-unsaturated building blocks

  摘要：

  The reaction conditions of the ring-opening processes of 3-nitrothiophene 7a and of 3-nitrobenzo[b]thiophene 7b with pyrrolidine and silver nitrate were optimized as well as those of the subsequent S-methylation of the ensuing silver enethiolates 8a and 8b to 4-methylthio-2-nitro-1-pyrrolidino-1,3-butadiene 9a and 1-(2-methylthiophenyl)-1-nitro-2-pyrrolidinoethylene 9b. Under such conditions 2-X-substituted 4-nitrothiophenes 7c-i consistently gave good yields of the corresponding 4-methylthio-2-nitro-1-pyrrolidino-4-X-1,3-butadienes 9c-i. The nitroenamine derivatives 9a-i were then reacted with p-tolylmagnesium bromide to furnish moderate to good yields of 4-methylthio-2-nitro-1-(p-tolyl)-4-X-1,3-butadienes 10a,c-i and 1-(2-methylthiophenyl)-1-nitro-2-(p-tolyl)ethylene 10b. Stereochemistry of the interesting building blocks 9a-i and 10a-i was assigned on the grounds of H-1 NMR data and NOE experiments. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(01)00765-7

文献信息

• Ring opening of 2-substituted 4-nitrothiophenes with pyrrolidine. Access to new functionalized nitro-unsaturated building blocks
  作者：Carlo Dell'Erba、Antonella Gabellini、Marino Novi、Giovanni Petrillo、Cinzia Tavani、Barbara Cosimelli、Domenico Spinelli

  DOI：10.1016/s0040-4020(01)00765-7

  日期：2001.9

  The reaction conditions of the ring-opening processes of 3-nitrothiophene 7a and of 3-nitrobenzo[b]thiophene 7b with pyrrolidine and silver nitrate were optimized as well as those of the subsequent S-methylation of the ensuing silver enethiolates 8a and 8b to 4-methylthio-2-nitro-1-pyrrolidino-1,3-butadiene 9a and 1-(2-methylthiophenyl)-1-nitro-2-pyrrolidinoethylene 9b. Under such conditions 2-X-substituted 4-nitrothiophenes 7c-i consistently gave good yields of the corresponding 4-methylthio-2-nitro-1-pyrrolidino-4-X-1,3-butadienes 9c-i. The nitroenamine derivatives 9a-i were then reacted with p-tolylmagnesium bromide to furnish moderate to good yields of 4-methylthio-2-nitro-1-(p-tolyl)-4-X-1,3-butadienes 10a,c-i and 1-(2-methylthiophenyl)-1-nitro-2-(p-tolyl)ethylene 10b. Stereochemistry of the interesting building blocks 9a-i and 10a-i was assigned on the grounds of H-1 NMR data and NOE experiments. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Design, synthesis, and in vitro evaluation of new naphthylnitrobutadienes with potential antiproliferative activity: Toward a structure/activity correlation
  作者：Giovanni Petrillo、Maria A. Mariggiò、Cinzia Aiello、Cinzia Cordazzo、Carla Fenoglio、Stefano Morganti、Michela Croce、Egon Rizzato、Domenico Spinelli、Massimo Maccagno、Lara Bianchi、Claudia Prevosto、Cinzia Tavani、Maurizio Viale

  DOI：10.1016/j.bmc.2007.09.042

  日期：2008.1

  On the grounds of previous encouraging results on the antitumor activity of (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1, 3-butadiene (1), we have designed and synthesized two new molecules [(1E,3E)-1,4-bis(4-carboxy-1-naphthyl)-2,3-dinitro-1,3-butadiene (2) and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (3)] characterized by a common naphthyl-nitrobutadiene array but with different structural properties, with the aim of approaching to some structure-activity correlation. When 2 and 3 were analyzed in vitro for their inhibition of cell proliferation and pro-apoptotic properties, the carboxyderivative 2 did not furnish appreciable results. In contrast, 3 (which contains only one of the two naphthyinitroethenyl moieties of the original compound 1) showed remarkable activities in the range of micromolar concentrations (in six over eight cell lines its IC(50)s are in the 1-3 mu M range), with a significant improvement compared to 1. In particular, 3 proved able to bind to DNA, to upregulate p53, to block cells in the G2/M phase of their cycle, and to induce apoptosis. Thus, very interestingly, the performance of 3 with respect to 1 shows that a single 1-(1-naphthyl)-2-nitroethene moiety is able to ensure better (on four out of eight of the cell lines tested) or comparable levels of activity. This result suggests that the 'molecular-simplification strategy' could furnish a useful instrument for future design in our antitumor research. (C) 2007 Elsevier Ltd. All rights reserved.