2-bromo-5-isobutyl-4-[(5-phosphono)furan-2-yl]thiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-bromo-5-isobutyl-4-[(5-phosphono)furan-2-yl]thiazole
• 英文别名: 2-bromo-5-isobutyl-4-[2-(5-phosphono)furanyl]thiazole；[5-[2-bromo-5-(2-methylpropyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid
• 化学式: C₁₁H₁₃BrNO₄PS
• 分子量: 366.172
• InChiKey: NQCCBLZEGQMRKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-甲基戊酸 在 盐酸 、 正丁基锂 、 三甲基溴硅烷 、 三氟化硼乙醚 、 对甲苯磺酸 、 三氟乙酸酐 、 copper(ll) bromide 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 氯仿 、 水 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 20.0h， 生成 2-bromo-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

文献信息

• Heteroaromatic compounds containing a phosphonate group that are inhibitors of fructose-1,6-bisphosphatase
  申请人：Metabasis Therapeutics, Inc.

  公开号：US06489476B1

  公开（公告）日：2002-12-03

  FBPase inhibitors of the formula I and X are useful in the treatment of diabetes and other conditions associated with elevated blood glucose or excess glycogen storage.

  公式I和X的FBPase抑制剂在治疗糖尿病和其他与血糖升高或多余糖原贮存有关的疾病中很有用。
• Novel bisamidate phosphonate prodrugs
  申请人：METABASIS THERAPEUTICS, INC.

  公开号：US20020173490A1

  公开（公告）日：2002-11-21

  Novel bisamidate phosphonate prodrugs of FBPase inhibitors of the Formula IA: 1 and their use in the treatment of diabetes and other conditions associated with elevated blood glucose.

  新颖的双酰胺磷酸酯前药，用于治疗糖尿病和其他与血糖升高相关的疾病的Formula IA:1中的FBPase抑制剂及其用途。