(2-amino-5-methoxyphenyl)-(4-isopropylphenyl)methanone | 478964-53-3

• 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: (2-amino-5-methoxyphenyl)-(4-isopropylphenyl)methanone
• 英文别名: (2-Amino-5-methoxy-phenyl)-(4-isopropyl-phenyl)-methanone；(2-amino-5-methoxyphenyl)-(4-propan-2-ylphenyl)methanone
• CAS: 478964-53-3
• 化学式: C₁₇H₁₉NO₂
• 分子量: 269.343
• InChiKey: UOMQVFOQZBKTFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  potassium carbonate 、 2-(2-溴乙基)吡啶氢溴酸盐 、 (2-amino-5-methoxyphenyl)-(4-isopropylphenyl)methanone 在 Brine 、 ethyl acetate n-hexane 作用下， 以 丙酮 、 乙酸乙酯 为溶剂， 反应 48.0h， 生成 (4-Isopropyl-phenyl)-{5-methoxy-2-[(pyridin-2-ylmethyl)-amino]-phenyl}-methanone
  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：

  (4-isopropylphenyl)-(5-methoxy-2-nitro-phenyl)methanone 在 镍 乙醚 、 盐酸 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 (2-amino-5-methoxyphenyl)-(4-isopropylphenyl)methanone
  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

文献信息

• Quinazoline derivatives
  申请人：——

  公开号：US20040180912A1

  公开（公告）日：2004-09-16

  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. 1

  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。
• 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
• US8476286B2
  申请人：——

  公开号：US8476286B2

  公开（公告）日：2013-07-02
• [EN] QUINAZOLINE DERIVATIVES<br/>[FR] DERIVES DE LA QUINAZOLINE
  申请人：NOVARTIS AG

  公开号：WO2002102782A2

  公开（公告）日：2002-12-27

  Use of compound of formula (I), wherein (a) is (b) or (c) 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.
• 1-Alkyl-4-phenyl-6-alkoxy-1<i>H</i>-quinazolin-2-ones: A Novel Series of Potent Calcium-Sensing Receptor Antagonists
  作者：Leo Widler、Eva Altmann、René Beerli、Werner Breitenstein、Rochdi Bouhelal、Thomas Buhl、Rainer Gamse、Marc Gerspacher、Christine Halleux、Markus R. John、Hansjoerg Lehmann、Oskar Kalb、Michaela Kneissel、Martin Missbach、Irene R. Müller、Sibylle Reidemeister、Johanne Renaud、Agnes Taillardat、Ruben Tommasi、Sven Weiler、Romain M. Wolf、Klaus Seuwen

  DOI：10.1021/jm901811v

  日期：2010.3.11

  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.