2-methyl-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-methyl-5-isobutyl-4-[(5-phosphono)furan-2-yl]thiazole
• 英文别名: 5-isobutyl-2-methyl-4-(2-(5-phosphono)furanyl)thiazole；2-methyl-5-isobutyl-4-[2-(5-phosphono)furanyl]thiazole；2-Methyl-5-isobutyl-4-[2-(5-phosphono)furanyl]-thiazole；[5-[2-methyl-5-(2-methylpropyl)-1,3-thiazol-4-yl]furan-2-yl]phosphonic acid
• 化学式: C₁₂H₁₆NO₄PS
• 分子量: 301.303
• InChiKey: DCDMCCKVTDICCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methyl-5-isobutyl-4-[(5-phosphono)furan-2-yl]thiazole 、 3-氨基-3-苯基-1-丙醇 在 吡啶 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 2-methyl-5-isobutyl-4-{2-[5-(1-phenyl-1,3-propyl)phosphonamido]furanyl}thiazole
  参考文献：
  名称：

  Novel phosphorus-containing prodrug

  摘要：

  新型循环磷酰胺酯前药，其父药物MH的化学式I 描述了它们在药物输送到肝脏中的应用，它们在增强口服生物利用度中的应用，以及它们的制备方法。

  公开号：

  EP1634886A3
• 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 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 为溶剂， 反应 36.0h， 生成 2-methyl-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

• Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes
  申请人：Metabasis Therapeutics, Inc.

  公开号：US06756360B1

  公开（公告）日：2004-06-29

  Pharmaceutical compositions containing an FBPase inhibitor and an insulin sensitizer are provided as well as methods for treating diabetes and diseases responding to increased glycemic control, an improvement in insulin sensitivity, a reduction in insulin levels, or an enhancement of insulin secretion.

  提供含有FBPase抑制剂和胰岛素增敏剂的药物组合物，以及治疗糖尿病和对增加糖代谢控制、改善胰岛素敏感性、降低胰岛素水平或增强胰岛素分泌有响应的疾病的方法。