6-(4-chlorophenyl)-3-{2-[(4-phenylpiperidin-1-yl)methyl]quinolin-6-yl}thieno[3,2-d]pyrimidin-4(3H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 6-(4-chlorophenyl)-3-{2-[(4-phenylpiperidin-1-yl)methyl]quinolin-6-yl}thieno[3,2-d]pyrimidin-4(3H)-one
• 英文别名: 6-(4-chlorophenyl)-3-{2-[(4-phenyl-1-piperidinyl)methyl]-6-quinolinyl}thieno[3,2-d]pyrimidin-4(3H)-one；6-(4-chlorophenyl)-3-[2-[(4-phenylpiperidin-1-yl)methyl]quinolin-6-yl]thieno[3,2-d]pyrimidin-4-one
• 化学式: C₃₃H₂₇ClN₄OS
• 分子量: 563.123
• InChiKey: ODMRZHCWTPHENJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 5-(4-chlorophenyl)-3-{[(1E)-(dimethylamino)methylidene]amino}-2-thiophenecarboxylate 、 2-[(4-苯基-1-哌啶基)甲基]-6-喹啉胺 以 苯酚 为溶剂， 反应 1.5h， 生成 6-(4-chlorophenyl)-3-{2-[(4-phenylpiperidin-1-yl)methyl]quinolin-6-yl}thieno[3,2-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  Potent, Selective, and Orally Efficacious Antagonists of Melanin-Concentrating Hormone Receptor 1

  摘要：

  The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists. In general, a good correlation was observed between pK(a)s and activity in the right-hand side of the template, with Asp123 playing an important role in the enhancement of binding affinity. A representative example when evaluated chronically in diet-induced obese mice resulted in good weight loss effects. These antagonists provide a viable lead series in the discovery of new therapies for the treatment of obesity.

  DOI：

  10.1021/jm060572f

文献信息

• Heterocyclic mchr1 antagoists
  申请人：Barvian K Kevin

  公开号：US20060194871A1

  公开（公告）日：2006-08-31

  This invention relates to novel heterocycles which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), also referred to as 11 CBy, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in medicines. Compounds of the invention have the formula:

  这项发明涉及新型杂环化合物，它们是黑色素聚集激素受体1（MCHR1）的拮抗剂，也被称为11 CBy，涉及含有这些化合物的药物组合物，制备这些化合物的过程，以及它们在药物中的用途。发明的化合物具有以下公式：
• [EN] HETEROCYCLIC MCHR1 ANTAGONISTS<br/>[FR] ANTAGONISTES HETEROCYCLIQUES DE MCHR1
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004092181A1

  公开（公告）日：2004-10-28

  This invention relates to novel heterocycles which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), also referred to as 11CBy, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in medicines. Compounds of the invention have formula (I).

  本发明涉及一种新型杂环，其是黑色素浓集激素受体1（MCHR1）的拮抗剂，也称为11CBy，以及包含它们的制药组合物，它们的制备过程和它们在药物中的用途。 本发明的化合物具有公式（I）。
• EP1618112A1
  申请人：——

  公开号：EP1618112A1

  公开（公告）日：2006-01-25
• Potent, Selective, and Orally Efficacious Antagonists of Melanin-Concentrating Hormone Receptor 1
  作者：Francis X. Tavares、Kamal A. Al-Barazanji、Eric C. Bigham、Michael J. Bishop、Christy S. Britt、David L. Carlton、Paul L. Feldman、Aaron S. Goetz、Mary K. Grizzle、Yu C. Guo、Anthony L. Handlon、Donald L. Hertzog、Diane M. Ignar、Daniel G. Lang、Ronda J. Ott、Andrew J. Peat、Hui-Qiang Zhou

  DOI：10.1021/jm060572f

  日期：2006.11.30

  The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists. In general, a good correlation was observed between pK(a)s and activity in the right-hand side of the template, with Asp123 playing an important role in the enhancement of binding affinity. A representative example when evaluated chronically in diet-induced obese mice resulted in good weight loss effects. These antagonists provide a viable lead series in the discovery of new therapies for the treatment of obesity.