5-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-1H-pyrazole-3-carboxylic acid | 1417577-17-3

• 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: 5-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-1H-pyrazole-3-carboxylic acid
• CAS: 1417577-17-3
• 化学式: C₁₅H₁₂N₄O₃S
• 分子量: 328.351
• InChiKey: OYOCYCDDKHDVMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Fmoc-L-丙氨酸 、 5-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-1H-pyrazole-3-carboxylic acid 在 哌啶 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 (2S)-2-[[5-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-1H-pyrazole-3-carbonyl]amino]propanoic acid
  参考文献：
  名称：

  Identification of inhibitors against interaction between pro-inflammatory sPLA2-IIA protein and integrin αvβ3

  摘要：

  Increased concentrations of secreted phospholipase A2 type IIA (sPLA2-IIA), have been found in the synovial fluid of patients with rheumatoid arthritis. It has been shown that sPLA2-IIA specifically binds to integrin alpha v beta 3, and initiates a signaling pathway that leads to cell proliferation and inflammation. Therefore, the interaction between integrin and sPLA2-IIA could be a potential therapeutic target for the treatment of proliferation or inflammation-related diseases. Two one-bead-one-compound peptide libraries were constructed and screened, and seven target hits were identified. Herein we report the identification, synthesis, and biological testing of two pyrazolylthiazole-tethered peptide hits and their analogs. Biological assays showed that these compounds were able to suppress the sPLA2-IIA-integrin interaction and sPLA2-IIA-induced migration of monocytic cells and that the blockade of the sPLA2-IIA-integrin binding was specific to sPLA2-IIA and not to the integrin. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.10.080
• 作为产物：
  描述：

  5-乙酰基-2-氨基-4-甲基噻唑 在 4-二甲氨基吡啶 、 三乙胺 、 N,N'-羰基二咪唑 、 sodium hydroxide 、 lithium hexamethyldisilazane 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 83.75h， 生成 5-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Efficient synthesis and cell migration inhibitory effect of substituted benzamidothiazolylpyrazole-capped AWD*I-NH2

  摘要：

  Substituted (2-benzamidothiazol-5-yl)pyrazole-capped AWD*I-NH2 were synthesized and their antimigration activity was studied. The improved efficiency and scalability of the analog synthesis was achieved via a late-stage diversification of the benzoyl group and a convergent route in which the bisazole capping agents and off-resin peptide AWD*I-NH2 were prepared in parallel and coupled together in solution at the last step. Bioassay results indicate that all the peptidomimetics can significantly inhibit the migration of breast cancer cells MDA-MB-231 but possess no apparent cytotoxicity. In general, the antimigration potency of the peptidomimetics is correlated to the electron-withdrawing capacity of the substituents on the terminal phenyl ring. The inhibitory effect shows dose-dependent and holds also against lung and cervical cancer cells. The level of f-actin was reduced dramatically in cells treated with the inhibitor, suggesting that the migration inhibitory effect is related to the disruption of cell locomotive protrusions.

  DOI：

  10.1016/j.bmcl.2019.126914

文献信息

• 一种酯基吡唑联噻唑胺化合物及其制备方法和应用
  申请人：武汉科技大学

  公开号：CN111606902A

  公开（公告）日：2020-09-01

  本发明公开了一种酯基吡唑联噻唑胺化合物及其制备方法和应用，其结构通式为：。该化合物是一种双五元氮杂环双官能团化合物，便于实现噻唑胺和吡唑的高通量合成和多样化衍生，可广泛应用于噻唑联吡唑类药物研发和生产中。
• Identification of inhibitors against interaction between pro-inflammatory sPLA2-IIA protein and integrin αvβ3
  作者：Long Ye、Tiffany Dickerson、Handeep Kaur、Yoko K. Takada、Masaaki Fujita、Ruiwu Liu、John M. Knapp、Kit S. Lam、Neil E. Schore、Mark J. Kurth、Yoshikazu Takada

  DOI：10.1016/j.bmcl.2012.10.080

  日期：2013.1

  Increased concentrations of secreted phospholipase A2 type IIA (sPLA2-IIA), have been found in the synovial fluid of patients with rheumatoid arthritis. It has been shown that sPLA2-IIA specifically binds to integrin alpha v beta 3, and initiates a signaling pathway that leads to cell proliferation and inflammation. Therefore, the interaction between integrin and sPLA2-IIA could be a potential therapeutic target for the treatment of proliferation or inflammation-related diseases. Two one-bead-one-compound peptide libraries were constructed and screened, and seven target hits were identified. Herein we report the identification, synthesis, and biological testing of two pyrazolylthiazole-tethered peptide hits and their analogs. Biological assays showed that these compounds were able to suppress the sPLA2-IIA-integrin interaction and sPLA2-IIA-induced migration of monocytic cells and that the blockade of the sPLA2-IIA-integrin binding was specific to sPLA2-IIA and not to the integrin. (C) 2012 Published by Elsevier Ltd.
• Efficient synthesis and cell migration inhibitory effect of substituted benzamidothiazolylpyrazole-capped AWD*I-NH2
  作者：Mian Yang、Jun Chen、Wancai Peng、Qiqi Li、Hui Shao、Guanping Tang、Tong-Cun Zhang、Yoshikazhu Takada、Long Ye、Xing-Hua Liao

  DOI：10.1016/j.bmcl.2019.126914

  日期：2020.2

  Substituted (2-benzamidothiazol-5-yl)pyrazole-capped AWD*I-NH2 were synthesized and their antimigration activity was studied. The improved efficiency and scalability of the analog synthesis was achieved via a late-stage diversification of the benzoyl group and a convergent route in which the bisazole capping agents and off-resin peptide AWD*I-NH2 were prepared in parallel and coupled together in solution at the last step. Bioassay results indicate that all the peptidomimetics can significantly inhibit the migration of breast cancer cells MDA-MB-231 but possess no apparent cytotoxicity. In general, the antimigration potency of the peptidomimetics is correlated to the electron-withdrawing capacity of the substituents on the terminal phenyl ring. The inhibitory effect shows dose-dependent and holds also against lung and cervical cancer cells. The level of f-actin was reduced dramatically in cells treated with the inhibitor, suggesting that the migration inhibitory effect is related to the disruption of cell locomotive protrusions.