N-[4-(5-diethoxyphosphorylfuran-2-yl)-5-(2-methylpropyl)-1,3-thiazol-2-yl]acetamide | 1259092-91-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[4-(5-diethoxyphosphorylfuran-2-yl)-5-(2-methylpropyl)-1,3-thiazol-2-yl]acetamide
• CAS: 1259092-91-5
• 化学式: C₁₇H₂₅N₂O₅PS
• 分子量: 400.436
• InChiKey: GAGRSZBQHIVGAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[4-(5-diethoxyphosphorylfuran-2-yl)-5-(2-methylpropyl)-1,3-thiazol-2-yl]acetamide 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 生成 2-acetamido-5-isobutyl-4-[(5-phosphono)furan-2-yl]thiazole
  参考文献：
  名称：

  Discovery of a Series of Phosphonic Acid-Containing Thiazoles and Orally Bioavailable Diamide Prodrugs That Lower Glucose in Diabetic Animals Through Inhibition of Fructose-1,6-Bisphosphatase

  摘要：

  Oral delivery of previously disclosed purine and benzimidazole fructose-1,6 bisphosphatase (FBPase) inhibitors via prodrugs failed, which was likely due to their high molecular wright (> 600) Therefore, a smaller scaffold was desired, and a series of phosphonic acid-containing thiazoles, which exhibited high potency against human liver FBPase (IC(50) of 10-30 nM) and high selectivity relative to other 5'-adenosinemonophosphate (AMP)-binding enzymes, were discovered using a structure-guided drug design approach The initial lead compound (30j) produced profound glucose lowering in rodent models of type 2 diabetes mellitus (T2DM) after parenteral administration Various phosphonate prodrugs were explored without success, until a novel phosphonic diamide prodrug approach was Implemented, which delivered compound 30j with good oral bioavailability (OBAV) (22-47%) Extensive lead optimization of both the thiazole FBPase inhibitors and their prodrugs culminated in the discovery of compound 35n (MB06322) as the first oral FBPase inhibitor advancing to human clinical trials as a potential treatment for T2DM

  DOI：

  10.1021/jm101035x
• 作为产物：
  描述：

  4-甲基戊酸 在 盐酸 、 正丁基锂 、 三氟化硼乙醚 、 对甲苯磺酸 、 三氟乙酸酐 、 copper(ll) bromide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 氯仿 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 20.0h， 生成 N-[4-(5-diethoxyphosphorylfuran-2-yl)-5-(2-methylpropyl)-1,3-thiazol-2-yl]acetamide
  参考文献：
  名称：

  Discovery of a Series of Phosphonic Acid-Containing Thiazoles and Orally Bioavailable Diamide Prodrugs That Lower Glucose in Diabetic Animals Through Inhibition of Fructose-1,6-Bisphosphatase

  摘要：

  Oral delivery of previously disclosed purine and benzimidazole fructose-1,6 bisphosphatase (FBPase) inhibitors via prodrugs failed, which was likely due to their high molecular wright (> 600) Therefore, a smaller scaffold was desired, and a series of phosphonic acid-containing thiazoles, which exhibited high potency against human liver FBPase (IC(50) of 10-30 nM) and high selectivity relative to other 5'-adenosinemonophosphate (AMP)-binding enzymes, were discovered using a structure-guided drug design approach The initial lead compound (30j) produced profound glucose lowering in rodent models of type 2 diabetes mellitus (T2DM) after parenteral administration Various phosphonate prodrugs were explored without success, until a novel phosphonic diamide prodrug approach was Implemented, which delivered compound 30j with good oral bioavailability (OBAV) (22-47%) Extensive lead optimization of both the thiazole FBPase inhibitors and their prodrugs culminated in the discovery of compound 35n (MB06322) as the first oral FBPase inhibitor advancing to human clinical trials as a potential treatment for T2DM

  DOI：

  10.1021/jm101035x

文献信息

• Discovery of a Series of Phosphonic Acid-Containing Thiazoles and Orally Bioavailable Diamide Prodrugs That Lower Glucose in Diabetic Animals Through Inhibition of Fructose-1,6-Bisphosphatase
  作者：Qun Dang、Yan Liu、Daniel K. Cashion、Srinivas Rao Kasibhatla、Tao Jiang、Frank Taplin、Jason D. Jacintho、Haiqing Li、Zhili Sun、Yi Fan、Jay DaRe、Feng Tian、Wenyu Li、Tony Gibson、Robert Lemus、Paul D. van Poelje、Scott C. Potter、Mark D. Erion

  DOI：10.1021/jm101035x

  日期：2011.1.13

  Oral delivery of previously disclosed purine and benzimidazole fructose-1,6 bisphosphatase (FBPase) inhibitors via prodrugs failed, which was likely due to their high molecular wright (> 600) Therefore, a smaller scaffold was desired, and a series of phosphonic acid-containing thiazoles, which exhibited high potency against human liver FBPase (IC(50) of 10-30 nM) and high selectivity relative to other 5'-adenosinemonophosphate (AMP)-binding enzymes, were discovered using a structure-guided drug design approach The initial lead compound (30j) produced profound glucose lowering in rodent models of type 2 diabetes mellitus (T2DM) after parenteral administration Various phosphonate prodrugs were explored without success, until a novel phosphonic diamide prodrug approach was Implemented, which delivered compound 30j with good oral bioavailability (OBAV) (22-47%) Extensive lead optimization of both the thiazole FBPase inhibitors and their prodrugs culminated in the discovery of compound 35n (MB06322) as the first oral FBPase inhibitor advancing to human clinical trials as a potential treatment for T2DM