ethyl (5-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl}-2H-tetrazol-2-yl)acetate | 1030613-22-9

• 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: ethyl (5-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl}-2H-tetrazol-2-yl)acetate
• 英文别名: ethyl (5-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-[1,3,4]-thiadiazol-2-yl}-2H-tetrazol-2-yl)acetate；Ethyl 2-[5-[5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl]tetrazol-2-yl]acetate
• CAS: 1030613-22-9
• 化学式: C₁₈H₁₉BrFN₇O₃S
• 分子量: 512.362
• InChiKey: NWTGBLVGXZMXPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  136
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  ethyl (5-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl}-2H-tetrazol-2-yl)acetate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以92%的产率得到5-[5-[4-(2-溴-5-氟苯氧基)-1-哌啶基]-1,3,4-噻二唑-2-基]-2H-四唑-2-乙酸
  参考文献：
  名称：

  Development of a Liver-Targeted Stearoyl-CoA Desaturase (SCD) Inhibitor (MK-8245) to Establish a Therapeutic Window for the Treatment of Diabetes and Dyslipidemia

  摘要：

  The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing so, we set out to target the SCD inhibitor to the organ believed to be responsible for the therapeutic efficacy (liver) while minimizing its exposure in the tissues associated with mechanism-based SCD depletion of essential lubricating lipids (skin and eye). These efforts led to the discovery of MK-8245 (7), a potent, liver-targeted SCD inhibitor with preclinical antidiabetic and antidyslipidemic efficacy with a significantly improved therapeutic window.

  DOI：

  10.1021/jm200319u
• 作为产物：
  描述：

  4-(2-溴-5-氟苯氧基)哌啶盐酸盐 在 sodium azide 、 吡啶盐酸盐 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.0h， 生成 ethyl (5-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl}-2H-tetrazol-2-yl)acetate 、 ethyl (5-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl}-1H-tetrazol-1-yl)acetate
  参考文献：
  名称：

  Development of a Liver-Targeted Stearoyl-CoA Desaturase (SCD) Inhibitor (MK-8245) to Establish a Therapeutic Window for the Treatment of Diabetes and Dyslipidemia

  摘要：

  The potential use of SCD inhibitors for the chronic treatment of diabetes and dyslipidemia has been limited by preclinical adverse events associated with inhibition of SCD in skin and eye tissues. To establish a therapeutic window, we embarked on designing liver-targeted SCD inhibitors by utilizing molecular recognition by liver-specific organic anion transporting polypeptides (OATPs). In doing so, we set out to target the SCD inhibitor to the organ believed to be responsible for the therapeutic efficacy (liver) while minimizing its exposure in the tissues associated with mechanism-based SCD depletion of essential lubricating lipids (skin and eye). These efforts led to the discovery of MK-8245 (7), a potent, liver-targeted SCD inhibitor with preclinical antidiabetic and antidyslipidemic efficacy with a significantly improved therapeutic window.

  DOI：

  10.1021/jm200319u