N-{(5-carboxy-X-rhodaminyl)but-4-yl}-2-{1-(4-chlorobenzoyl)-5-methoxy-2′-trifluoromethyl-1H-indol-3-yl}-acetamide | 1537876-09-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-{(5-carboxy-X-rhodaminyl)but-4-yl}-2-{1-(4-chlorobenzoyl)-5-methoxy-2′-trifluoromethyl-1H-indol-3-yl}-acetamide
• 英文别名: CF3-fluorocoxib A
• CAS: 1537876-09-7
• 化学式: C₅₆H₅₁ClF₃N₅O₇
• 分子量: 998.498
• InChiKey: JFTQYARXPVMYLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.68
• 重原子数：
  72.0
• 可旋转键数：
  12.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  145.04
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  CF3-indomethacin 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.08h， 生成 N-{(5-carboxy-X-rhodaminyl)but-4-yl}-2-{1-(4-chlorobenzoyl)-5-methoxy-2′-trifluoromethyl-1H-indol-3-yl}-acetamide
  参考文献：
  名称：

  Trifluoromethyl Fluorocoxib A Detects Cyclooxygenase-2 Expression in Inflammatory Tissues and Human Tumor Xenografts

  摘要：

  Fluorocoxib A is an effective COX-2-targeted optical imaging agent, used for in vivo detection of inflammatory tissues and premalignant and malignant tumors that express elevated levels of COX-2 (Uddin et al. Cancer Res. 2010, 70, 3618-3627). In an effort to discover novel optical probes for COX-2, a trifluoromethyl analogue of fluorocoxib A (CF3-fluorocoidb A) was synthesized and evaluated for its ability to inhibit COX-2 in vitro purified enzyme and human cancer cell lines. Kinetic analysis revealed that CF3-fluorocoxib A is a slow, tight binding inhibitor of COX-2 that exhibits low nanomolar inhibitory potency. While CF3-fluorocoxib A and fluorocoxib A are similar in structure, CF3-fluorocoxib A shows improved potency in inhibition of wtC0X-2 and with a series of site-directed COX-2 mutants. After intraperitoneal injection, selective uptake of CF3-fluorocoxib A is detected in inflamed mouse paws compared to noninflamed contralateral paws by optical imaging, and uptake is blocked by pretreatment with the COX-2 inhibitor, celecoxib. Selective uptake is also detected in the COX-2-positive human tumor xenografts (1483 HNSCC) as compared with the COX-2-negative tumor xenografts (HCT116) in an in vivo nude mouse tumor model. These in vitro and in vivo studies suggest that binding to COX-2 is the major determinant of uptake of CF3-fluorocoxib A into the inflamed tissues and tumor xenografts. Thus, this new COX-2-targeted imaging probe should find utility in the detection and evaluation of COX-2 status in naturally occurring malignancies.

  DOI：

  10.1021/ml400485g