4-(1-isopropyl-6-methoxy-2-oxo-1,2-dihydro-quinazolin-4-yl)benzoic acid methyl ester | 1207345-17-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(1-isopropyl-6-methoxy-2-oxo-1,2-dihydro-quinazolin-4-yl)benzoic acid methyl ester
• 英文别名: 4-(1-Isopropyl-6-methoxy-2-oxo-1,2-dihydro-quinazolin-4-yl)-benzoic acid methyl ester；methyl 4-(6-methoxy-2-oxo-1-propan-2-ylquinazolin-4-yl)benzoate
• CAS: 1207345-17-2
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: IXKAKFWEQZXNCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(1-isopropyl-6-methoxy-2-oxo-1,2-dihydro-quinazolin-4-yl)benzoic acid methyl ester 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以44%的产率得到4-(1-isopropyl-6-methoxy-2-oxo-tetrahydro-quinazolin-4-yl)benzoic acid
  参考文献：
  名称：

  1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: A Novel Series of Potent Calcium-Sensing Receptor Antagonists

  摘要：

  Parathyroid hormone (PTH) is an effective bone anabolic agent. However, only when administered by daily sc injections exposure of short duration is achieved, a prerequisite for an anabolic response. Instead of applying exogenous PTH, mobilization of endogenous stores of the hormone can be envisaged. The secretion of PTH stored in the parathyroid glands is mediated by a calcium Sensing receptor (CaSR) a GPCR localized at the cell surface. Antagonists of CaSR (calcilytics) mimic a state of hypocalcaemia and stimulate PTH release to the bloodstream. Screening of the internal compound collection for inhibition of CaSR signaling function afforded 2a. In vitro potency Could be improved > 1000 fold by optimization of its chemical structure. The binding mode of our compounds was predicted based oil molecular modeling and confirmed by testing with Mutated receptors. While the Compounds readily induced PTH release after iv application a special formulation was needed for oral activity. The required profile was achieved by using microemulsions. Excellent PK/PD correlation was found in rats and dogs. High levels of PTH were reached in plasma within Minutes which reverted to baseline in about 1-2 h in both species.

  DOI：

  10.1021/jm901811v
• 作为产物：
  描述：

  4-(1-isopropyl-6-methoxy-2-oxo-1,2,3,4-tetrahydro-quinazolin-4-yl)benzoic acid methyl ester 在 ruthenium trichloride 、 sodium periodate 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 72.0h， 以75%的产率得到4-(1-isopropyl-6-methoxy-2-oxo-1,2-dihydro-quinazolin-4-yl)benzoic acid methyl ester
  参考文献：
  名称：

  1-Alkyl-4-phenyl-6-alkoxy-1H-quinazolin-2-ones: A Novel Series of Potent Calcium-Sensing Receptor Antagonists

  摘要：

  Parathyroid hormone (PTH) is an effective bone anabolic agent. However, only when administered by daily sc injections exposure of short duration is achieved, a prerequisite for an anabolic response. Instead of applying exogenous PTH, mobilization of endogenous stores of the hormone can be envisaged. The secretion of PTH stored in the parathyroid glands is mediated by a calcium Sensing receptor (CaSR) a GPCR localized at the cell surface. Antagonists of CaSR (calcilytics) mimic a state of hypocalcaemia and stimulate PTH release to the bloodstream. Screening of the internal compound collection for inhibition of CaSR signaling function afforded 2a. In vitro potency Could be improved > 1000 fold by optimization of its chemical structure. The binding mode of our compounds was predicted based oil molecular modeling and confirmed by testing with Mutated receptors. While the Compounds readily induced PTH release after iv application a special formulation was needed for oral activity. The required profile was achieved by using microemulsions. Excellent PK/PD correlation was found in rats and dogs. High levels of PTH were reached in plasma within Minutes which reverted to baseline in about 1-2 h in both species.

  DOI：

  10.1021/jm901811v