1-(1-甲基乙基)-4-[4-(1-甲基乙基)苯基]-6-(2-丙炔-1-基氧基)-2(1H)-喹唑啉酮 | 478963-79-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1-(1-甲基乙基)-4-[4-(1-甲基乙基)苯基]-6-(2-丙炔-1-基氧基)-2(1H)-喹唑啉酮
• 中文别名: 1-(1-甲基乙基)-4-[4-(1-甲基乙基)苯基]-6-(2-丙炔-1-氧基)-2(1H)-喹唑啉
• 英文名称: 1-isopropyl-4-(4-isopropylphenyl)-6-propargyloxy-1H-quinazolin-2-one
• 英文别名: 1-isopropyl-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazoline-2-one；Calcium-Sensing Receptor Antagonists I；1-propan-2-yl-4-(4-propan-2-ylphenyl)-6-prop-2-ynoxyquinazolin-2-one
• CAS: 478963-79-0
• 化学式: C₂₃H₂₄N₂O₂
• 分子量: 360.456
• InChiKey: RXVZJHDMMKTKDR-UHFFFAOYSA-N

物化性质

• 沸点：
  510.1±60.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  2

制备方法与用途

生物活性

Calcium-Sensing Receptor Antagonists I 是一种针对钙离子敏感的甲状旁腺激素受体的拮抗剂。

反应信息

• 作为反应物：
  描述：

  1-(1-甲基乙基)-4-[4-(1-甲基乙基)苯基]-6-(2-丙炔-1-基氧基)-2(1H)-喹唑啉酮 在 劳森试剂 作用下， 以 苯 为溶剂， 生成 1-isopropyl-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazoline 2-thione
  参考文献：
  名称：

  [EN] DERIVATIVES OF ARYL-QUINAZOLINE/ARYL-2AMINO-PHENYL METHANONE WHICH PROMOTE THE RELEASE OF PARATHYROID HORMONE
  [FR] DERIVES D'ARYL-QUINAZOLINE/ARYL-2AMINO-PHENYL METHANONE

  摘要：

  公开号：

  WO2004056365A3
• 作为产物：
  描述：

  6-羟基-1-异丙基-4-(4-异丙基苯基)-1H-喹唑啉-2-酮 、 3-溴丙炔 在 caesium carbonate 作用下， 以 1,3-二甲基-2-咪唑啉酮 为溶剂， 反应 18.0h， 以90%的产率得到1-(1-甲基乙基)-4-[4-(1-甲基乙基)苯基]-6-(2-丙炔-1-基氧基)-2(1H)-喹唑啉酮
  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

文献信息

• Aryl-quinazoline/aryl-2amino-phenyl methanone derivatives
  申请人：Altmann Eva

  公开号：US20060079685A1

  公开（公告）日：2006-04-13

  A compound of formula (I): wherein R1, R2, R3 and Y are as defined herein, or a pharmaceutically-acceptable and -cleavable ester, or acid addition salt thereof, useful for promoting the release of parathyroid hormone, e.g. for preventing or treating bone conditions which are associated with increased calcium depletion or resorption or in which stimulation of bone formation and calcium fixation in the bone is desirable.

  化合物的化学式为(I): 其中R1，R2，R3和Y的定义如下，或其药学上可接受和可水解酯或酸盐，用于促进甲状旁腺激素的释放，例如预防或治疗与钙流失或吸收增加或骨形成和钙固定在骨中有关的骨病情况。
• Aryl-quinazoline/aryl-2-amino-phenyl methanone derivatives
  申请人：Novartis AG

  公开号：US07696216B2

  公开（公告）日：2010-04-13

  A compound of formula (I): wherein R1, R2, R3 and Y are as defined herein, or a pharmaceutically-acceptable and -cleavable ester, or acid addition salt thereof, useful for promoting the release of parathyroid hormone, e.g. for preventing or treating bone conditions which are associated with increased calcium depletion or resorption or in which stimulation of bone formation and calcium fixation in the bone is desirable.

  化合物的公式（I）：其中R1，R2，R3和Y的定义如下，或其药学上可接受和可水解酯，或酸盐，有助于促进甲状旁腺激素的释放，例如用于预防或治疗与增加的钙耗竭或吸收有关的骨病状况，或者在其中骨形成和钙固定在骨中是可取的。
• Derivatives of aryl-quinazoline/aryl-2-amino-phenyl methanone which promote the release of parathyroid hormone
  申请人：Novartis Pharma AG

  公开号：EP1844780A2

  公开（公告）日：2007-10-17

  A compound of formula I wherein R1, R2, R3 and Y are as defined herein, or a pharmaceutically-acceptable and -cleavable ester, or acid addition salt thereof, useful for promoting the release of parathyroid hormone, e.g. for preventing or treating bone conditions which are associated with increased calcium depletion or resorption or in which stimulation of bone formation and calcium fixation in the bone is desirable.

  式 I 的化合物 其中 R1、R2、R3 和 Y 如本文所定义、 或其药学上可接受和可清除的酯或酸加成盐、 可用于促进甲状旁腺激素的释放，例如用于预防或治疗与钙消耗或吸收增加有关的骨病，或用于刺激骨形成和钙在骨中的固定。
• Pharmaceutical compositions comprising a calcilytic agent
  申请人：Novartis AG

  公开号：EP1964548A1

  公开（公告）日：2008-09-03

  Provided is a pharmaceutical composition comprising a calcilytic agent which, when administered orally to a subject induces a rapid and short-lasting absorption of the calcilytic agent and/or a rapid and short-lasting release of the parathyroid hormone.

  本发明提供了一种药物组合物，其中包含一种降钙剂，当口服给受试者服用时，该药物组合物能诱导降钙剂的快速、短暂吸收和/或甲状旁腺激素的快速、短暂释放。
• QUINAZOLINE DERIVATIVES WHICH PROMOTE THE RELEASE OF PARATHYROID HORMONE
  申请人：Novartis AG

  公开号：EP1401451B1

  公开（公告）日：2009-11-11