(R)-2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-1-cyclopropylethyl bis(2-(trimethylsilyl)ethyl)phosphate | 1197420-26-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: (R)-2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-1-cyclopropylethyl bis(2-(trimethylsilyl)ethyl)phosphate
• 英文别名: (R)-2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-1-cyclopropyl-ethyl bis(2-(trimethylsilyl)ethyl) phosphate；[(1R)-2-[4-[6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3-yl]-2-methoxyphenoxy]-1-cyclopropylethyl] bis(2-trimethylsilylethyl) phosphate
• CAS: 1197420-26-0
• 化学式: C₃₄H₄₆ClN₂O₇PSSi₂
• 分子量: 749.412
• InChiKey: KSEKHNHMIHRJSC-HKBQPEDESA-N

物化性质

• 沸点：
  778.4±70.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.77
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (R)-2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-1-cyclopropylethyl bis(2-(trimethylsilyl)ethyl)phosphate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.58h， 以73.4%的产率得到BMS830216
  参考文献：
  名称：

  Identification of a Nonbasic Melanin Hormone Receptor 1 Antagonist as an Antiobesity Clinical Candidate

  摘要：

  Identification of MCHR1 antagonists with a preclinical safety profile to support clinical evaluation as antiobesity agents has been a challenge. Our finding that a basic moiety is not required for MCHR1 antagonists to achieve high affinity allowed us to explore structures less prone to off-target activities such as hERG inhibition. We report the SAR evolution of hydroxylated thienopyrimidinone ethers culminating in the identification of 27 (BMS-819881), which entered obesity clinical trials as the phosphate ester prodrug 35 (BMS-830216).

  DOI：

  10.1021/jm500026w
• 作为产物：
  描述：

  2-溴-1-环丙基乙酮 在 1H-1,2,4-三唑 、 sodium tetrahydroborate 、 5%-palladium/activated carbon 、 氢气 、 双氧水 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 、 苯酚 为溶剂， -3.0~130.0 ℃ 、101.33 kPa 条件下， 反应 25.58h， 生成 (R)-2-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-1-cyclopropylethyl bis(2-(trimethylsilyl)ethyl)phosphate
  参考文献：
  名称：

  Identification of a Nonbasic Melanin Hormone Receptor 1 Antagonist as an Antiobesity Clinical Candidate

  摘要：

  Identification of MCHR1 antagonists with a preclinical safety profile to support clinical evaluation as antiobesity agents has been a challenge. Our finding that a basic moiety is not required for MCHR1 antagonists to achieve high affinity allowed us to explore structures less prone to off-target activities such as hERG inhibition. We report the SAR evolution of hydroxylated thienopyrimidinone ethers culminating in the identification of 27 (BMS-819881), which entered obesity clinical trials as the phosphate ester prodrug 35 (BMS-830216).

  DOI：

  10.1021/jm500026w

文献信息

• HYDROXY SUBSTITUTED THIENO PYRIMIDINONES AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS
  申请人：Washburn William N.

  公开号：US20090298794A1

  公开（公告）日：2009-12-03

  The present invention provides compounds having the following Formula IA and IB, which are useful as MCHR1 antagonists, and includes prodrugs and pharmaceutically acceptable salts thereof:

  本发明提供了具有以下化学式IA和IB的化合物，这些化合物可作为MCHR1拮抗剂使用，并包括其前药和药用盐：
• Substituted thieno[3,2-D]pyrimidines as melanin concentrating hormone receptor-1 antagonists
  申请人：Bristol-Myers Squibb Company

  公开号：US07989433B2

  公开（公告）日：2011-08-02

  The present invention provides compounds having the following Formula IA and IB, which are useful as MCHR1 antagonists, and includes prodrugs and pharmaceutically acceptable salts thereof:

  本发明提供以下化合物IA和IB，它们可用作MCHR1拮抗剂，并包括其前药和药学上可接受的盐：
• J. Med. Chem. 2014, 57, 7509-7522
  作者：

  DOI：——

  日期：——