(4-Isopropyl-phenyl)-[2-(3-nitro-benzylamino)-5-propargyloxy-phenyl]-methanone | 478965-59-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-Isopropyl-phenyl)-[2-(3-nitro-benzylamino)-5-propargyloxy-phenyl]-methanone
• 英文别名: [2-[(3-nitrophenyl)methylamino]-5-prop-2-ynoxyphenyl]-(4-propan-2-ylphenyl)methanone
• CAS: 478965-59-2
• 化学式: C₂₆H₂₄N₂O₄
• 分子量: 428.488
• InChiKey: KJNKNVKZUBRSIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-Isopropyl-phenyl)-[2-(3-nitro-benzylamino)-5-propargyloxy-phenyl]-methanone 、 Sodium cyanate 在 乙酸乙酯 、 羟基甲酸酯 作用下， 以 溶剂黄146 、 水 为溶剂， 反应 16.0h， 生成 4-(4-isopropyl-phenyl)-1-(3-nitro-benzyl)-6-propargyloxy-1H-quinazolin-2-one
  参考文献：
  名称：

  Quinazoline derivatives

  摘要：

  使用公式（I）的化合物，其中，是，或，其中符号的定义如上所述，或其药学上可接受的可水解酯或酸盐，用于制备促进甲状旁腺激素释放的药物，例如用于预防或治疗与增加的钙耗竭或吸收有关的骨病或需要刺激骨形成和钙固定于骨中的情况。

  公开号：

  US20040180912A1
• 作为产物：
  描述：

  (2-amino-5-propargyloxy-phenyl)-(4-isopropylphenyl)methanone 、 3-硝基溴苄 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 (4-Isopropyl-phenyl)-[2-(3-nitro-benzylamino)-5-propargyloxy-phenyl]-methanone
  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

• Quinazoline derivatives which promote the release of parathyroid hormone
  申请人：Beerli René

  公开号：US08476286B2

  公开（公告）日：2013-07-02

  Use of compound of formula (I), wherein, is, or, and wherein the symbols are as defined, or a pharmaceutically-acceptable and -cleavable ester, or acid addition salt thereof, for the preparation of a medicament 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.

  使用公式（I）的化合物，其中，是，或，其中符号的定义如下，或其药学上可接受和可水解的酯，或酸加成盐，用于制备促进甲状旁腺激素释放的药物，例如用于预防或治疗与增加的钙耗竭或吸收有关的骨病或骨形成和钙固定在骨中受到欢迎的情况。
• 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
• PHARMACEUTICAL COMPOSITIONS COMPRISING A CALCILYTIC AGENT
  申请人：Novartis AG

  公开号：EP2124893A1

  公开（公告）日：2009-12-02
• PHARMACEUTICAL COMPOSITIONS
  申请人：Buhl Thomas

  公开号：US20100022565A1

  公开（公告）日：2010-01-28

  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.