(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：——
• Identification of a Nonbasic Melanin Hormone Receptor 1 Antagonist as an Antiobesity Clinical Candidate
  作者：William N. Washburn、Mark Manfredi、Pratik Devasthale、Guohua Zhao、Saleem Ahmad、Andres Hernandez、Jeffrey A. Robl、Wei Wang、James Mignone、Zhenghua Wang、Khehyong Ngu、Mary Ann Pelleymounter、Daniel Longhi、Rulin Zhao、Bei Wang、Ning Huang、Neil Flynn、Anthony V. Azzara、Joel C. Barrish、Kenneth Rohrbach、James J. Devenny、Suzanne Rooney、Michael Thomas、Susan Glick、Helen E. Godonis、Susan J. Harvey、Mary Jane Cullen、Hongwei Zhang、Christian Caporuscio、Paul Stetsko、Mary Grubb、Brad D. Maxwell、Hong Yang、Atsu Apedo、Brian Gemzik、Evan B. Janovitz、Christine Huang、Lisa Zhang、Chris Freeden、Brian J. Murphy

  DOI：10.1021/jm500026w

  日期：2014.9.25

  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).