6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one | 1026063-71-7

• 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: 6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one
• 英文别名: 6-(4-chlorophenyl)-3-[4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl]thieno[3,2-d]pyrimidin-4-one
• CAS: 1026063-71-7
• 化学式: C₂₃H₂₁ClN₂O₄S
• 分子量: 456.95
• InChiKey: GRPZZKMUWKOODM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  99.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one 在 4-二甲氨基吡啶 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 3-(1-(4-(6-(4-Chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yloxy)-3-oxopropanoic acid
  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：

  1-(2-methoxy-4-nitrophenoxy)-2-methylpropan-2-ol 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 21.0h， 生成 6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one
  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：
• [EN] HYDROXY SUBSTITUTED THIENO PYRIMIDINONES AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] THIÉNOPYRIMIDINONES HYDROXY-SUBSTITUÉES EN TANT QU'ANTAGONISTES DE RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009146365A1

  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.

  本发明提供具有以下化学式IA和IB的化合物，其作为MCHR1拮抗剂具有用途，并包括其前药和药学上可接受的盐。
• Non-basic melanin concentrating hormone receptor-1 antagonists
  申请人：Washburn N. William

  公开号：US20070093509A1

  公开（公告）日：2007-04-26

  The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I. Additionally, the present application provides pharmaceutical compositions containing at least one compound according to Formula I and optionally at least one additional therapeutic agent. Finally, the present application provides methods for treating a patient suffering from an MCHR-1 modulated disease or disorder such as, for example, obesity, diabetes, depression or anxiety by administration of a therapeutically effective dose of a compound according to Formula I.

  本申请提供了按照公式I提供的化合物，包括所有立体异构体、溶剂合物、前药和药学上可接受的形式。此外，本申请提供了含有至少一种按照公式I的化合物和可选的至少一种额外治疗剂的制药组合物。最后，本申请提供了通过给予按照公式I的化合物的治疗有效剂量来治疗患有MCHR-1调节的疾病或疾病，例如肥胖症、糖尿病、抑郁症或焦虑症的患者的方法。
• Substituted thieno[3,2-d]pyrimidinones as MCHR1 antagonists and methods for using them
  申请人：Washburn William N.

  公开号：US08618115B2

  公开（公告）日：2013-12-31

  The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I. Additionally, the present application provides pharmaceutical compositions containing at least one compound according to Formula I and optionally at least one additional therapeutic agent. Finally, the present application provides methods for treating a patient suffering from an MCHR-1 modulated disease or disorder such as, for example, obesity, diabetes, depression or anxiety by administration of a therapeutically effective dose of a compound according to Formula I.

  本申请提供了公式I所示的化合物，包括所有立体异构体、溶剂化物、前药和药学上可接受的形式。此外，本申请还提供了含有至少一种公式I化合物和可选的至少一种其他治疗剂的药物组合物。最后，本申请提供了通过给患有MCHR-1调节性疾病或疾病的患者以公式I化合物的治疗有效剂量来治疗患者的方法，例如肥胖症、糖尿病、抑郁症或焦虑症。
• Deoxyfluorination of 1°, 2°, and 3° Alcohols by Nonbasic O–H Activation and Lewis Acid-Catalyzed Fluoride Shuttling
  作者：Hye Won Moon、Marissa N. Lavagnino、Soohyun Lim、Maximilian D. Palkowitz、Michael D. Mandler、Gregory L. Beutner、Myles J. Drance、Jeffrey M. Lipshultz、Paul M. Scola、Alexander T. Radosevich

  DOI：10.1021/jacs.3c08373

  日期：2023.10.18

  A method for deoxyfluorination of aliphatic primary, secondary, and tertiary alcohols is reported, employing a nontrigonal phosphorus triamide for base-free alcohol activation in conjunction with an organic soluble fluoride donor and a triarylborane fluoride shuttling catalyst. Mechanistic experiments are consistent with a reaction that proceeds by the collapse of an oxyphosphonium fluoroborate ion

  报道了一种脂肪族伯醇、仲醇和叔醇脱氧氟化的方法，使用非三方磷三酰胺与有机可溶性氟化物供体和三芳基硼烷氟化物穿梭催化剂一起进行无碱醇活化。机理实验与氟硼酸氧鏻离子对塌陷和氟化物转移所进行的反应一致。该底物范围补充了现有的脱氧氟化方法，并能够通过底物醇的立体反转制备纯手性仲烷基氟和叔烷基氟。