4-(1,3-benzothiazol-2-yl)-3-(2,3-dimethylphenyl)-N-[[3-[(4-phenylphenyl)methyl]imidazol-4-yl]methyl]aniline

• 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: 4-(1,3-benzothiazol-2-yl)-3-(2,3-dimethylphenyl)-N-[[3-[(4-phenylphenyl)methyl]imidazol-4-yl]methyl]aniline
• 化学式: C₅H₈NO₃PolS
• 分子量: 576.8
• InChiKey: CQYCHFJGQAYMQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(1,3-benzothiazol-2-yl)-3-(2,3-dimethylphenyl)-N-[[3-[(4-phenylphenyl)methyl]imidazol-4-yl]methyl]aniline 在 tris-(tetra-n-butylammonium)thiolodiphosphate 、 碳酸氢铵 作用下， 以 四氢呋喃 、 乙腈 、 异丙醇 、 水 为溶剂， 反应 24.0h， 生成 trisodium S-(4-cyanobutyl) thiodiphosphate
  参考文献：
  名称：

  Thiopyrophosphoantigens: Solid-phase Synthesis and in Vitro Characterization of a New Class of Vγ9 Vδ2 T Cells Activators

  摘要：

  The V gamma 9 V delta 2 T cells mediate rapid, innate-like immune responses to pathogens and are important in several key immunoregulatory pathways, including those involved in infections and tumor development. V gamma 9 V delta 2 T cells respond to low molecular weight isoprenoid phosphoantigens; the prototypic stimulatory compound is isopentenylpyrophosphate (IPP), an alkylphosphate intermediate of mevalonate metabolism that elicits proliferative, cytotoxic, and cytokine secretion responses. We studied the replacement of the pyrophosphate moiety with the thiopyrophosphate bioisostere, synthesizing thioanalogues of IPP and 4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP, the most potent natural antigen known to date). Once their in vitro efficacy and stability had been demonstrated, we synthesized a small library of compounds through the development of an innovative solid-phase strategy. Biological results confirmed thioHMBPP to be the best compound of this first series. Future aims are (i) the exploitation of the parallel solid-phase strategy to further explore structure-activity relationships of this new class of synthetic antigens and (ii) the determination of the PK/PD profile of thioHMBPP.

  DOI：

  10.1021/jm900054u
• 作为产物：
  描述：

  PEG 4000-sulfonyl chloride 、 5-羟基-戊腈 在 吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 4-(1,3-benzothiazol-2-yl)-3-(2,3-dimethylphenyl)-N-[[3-[(4-phenylphenyl)methyl]imidazol-4-yl]methyl]aniline
  参考文献：
  名称：

  Thiopyrophosphoantigens: Solid-phase Synthesis and in Vitro Characterization of a New Class of Vγ9 Vδ2 T Cells Activators

  摘要：

  The V gamma 9 V delta 2 T cells mediate rapid, innate-like immune responses to pathogens and are important in several key immunoregulatory pathways, including those involved in infections and tumor development. V gamma 9 V delta 2 T cells respond to low molecular weight isoprenoid phosphoantigens; the prototypic stimulatory compound is isopentenylpyrophosphate (IPP), an alkylphosphate intermediate of mevalonate metabolism that elicits proliferative, cytotoxic, and cytokine secretion responses. We studied the replacement of the pyrophosphate moiety with the thiopyrophosphate bioisostere, synthesizing thioanalogues of IPP and 4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP, the most potent natural antigen known to date). Once their in vitro efficacy and stability had been demonstrated, we synthesized a small library of compounds through the development of an innovative solid-phase strategy. Biological results confirmed thioHMBPP to be the best compound of this first series. Future aims are (i) the exploitation of the parallel solid-phase strategy to further explore structure-activity relationships of this new class of synthetic antigens and (ii) the determination of the PK/PD profile of thioHMBPP.

  DOI：

  10.1021/jm900054u

文献信息

• Structurally Simple Inhibitors of Lanosterol 14α-Demethylase Are Efficacious In a Rodent Model of Acute Chagas Disease
  作者：Praveen Kumar Suryadevara、Srinivas Olepu、Jeffrey W. Lockman、Junko Ohkanda、Mandana Karimi、Christophe L. M. J. Verlinde、James M. Kraus、Jan Schoepe、Wesley C. Van Voorhis、Andrew D. Hamilton、Frederick S. Buckner、Michael H. Gelb

  DOI：10.1021/jm900030h

  日期：2009.6.25

  We report structure-activity studies of a large number of dialkyl imidazoles as inhibitors of Trypanosoma cruzi lanosterol-14 alpha-demethylase (L14DM). The compounds have a simple structure compared to posaconazole, another L14DM inhibitor that is an anti-Chagas drug candidate. Several compounds display potency for killing T cruzi amastigotes in vitro with values of EC50 in the 0.4-10 nM range. Two compounds were selected for efficacy studies in a mouse model of acute Chagas disease. At oral doses of 20-50 mg/kg given after establishment of parasite infection, the compounds reduced parasitemia in the blood to undetectable levels, and analysis of remaining parasites by PCR revealed a lack of parasites in the majority of animals. These dialkyl imidazoles are substantially less expensive to produce than posaconazole and are appropriate for further development toward an anti-Chagas disease clinical candidate.