1-(2,3-dimethyl-2H-indazol-5-yl)-4-{[5-(trifluoromethyl)thiophen-2-yl]methoxy}pyridin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 1-(2,3-dimethyl-2H-indazol-5-yl)-4-{[5-(trifluoromethyl)thiophen-2-yl]methoxy}pyridin-2(1H)-one
• 英文别名: 1-(2,3-dimethylindazol-5-yl)-4-[[5-(trifluoromethyl)thiophen-2-yl]methoxy]pyridin-2-one
• 化学式: C₂₀H₁₆F₃N₃O₂S
• 分子量: 419.427
• InChiKey: XWFNNLQMTXNZJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-苄氧基-2(1H)-吡啶酮 在 bis(2-methoxyethyl) azodicarboxylate 、 copper(l) iodide 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三苯基膦 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 9.0h， 生成 1-(2,3-dimethyl-2H-indazol-5-yl)-4-{[5-(trifluoromethyl)thiophen-2-yl]methoxy}pyridin-2(1H)-one
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUND
  [FR] COMPOSÉ HÉTÉROCYCLIQUE

  摘要：

  提供的是一种具有黑色素浓缩激素受体拮抗作用的化合物，可用作预防或治疗肥胖等疾病的药物。该化合物由以下式（I）表示：其中每个符号如规范中定义，或其盐。

  公开号：

  WO2015005489A1

文献信息

• [EN] HETEROCYCLIC COMPOUND<br/>[FR] COMPOSÉ HÉTÉROCYCLIQUE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2015005489A1

  公开（公告）日：2015-01-15

  Provided is a compound having a melanin-concentrating hormone receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of obesity and the like. A compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是一种具有黑色素浓缩激素受体拮抗作用的化合物，可用作预防或治疗肥胖等疾病的药物。该化合物由以下式（I）表示：其中每个符号如规范中定义，或其盐。
• Heterocyclic compound
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US09199963B2

  公开（公告）日：2015-12-01

  Provided is a compound having a melanin-concentrating hormone receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of obesity and the like. A compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  提供了一种具有黑色素浓聚激素受体拮抗作用的化合物，可用作预防或治疗肥胖等疾病的药物。该化合物由以下式子表示：（I）式中，每个符号如规范中所定义，或其盐。
• HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3019487A1

  公开（公告）日：2016-05-18
• US9199963B2
  申请人：——

  公开号：US9199963B2

  公开（公告）日：2015-12-01
• Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel non-basic 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives and mitigation of mutagenicity in Ames test
  作者：Hideyuki Igawa、Masashi Takahashi、Minoru Ikoma、Hiromi Kaku、Keiko Kakegawa、Asato Kina、Jumpei Aida、Shoki Okuda、Yayoi Kawata、Toshihiro Noguchi、Natsu Hotta、Syunsuke Yamamoto、Masaharu Nakayama、Yasutaka Nagisa、Shizuo Kasai、Tsuyoshi Maekawa

  DOI：10.1016/j.bmc.2016.04.013

  日期：2016.6

  To develop non-basic melanin-concentrating hormone receptor 1 (MCHR1) antagonists with a high probability of target selectivity and therapeutic window, we explored neutral bicyclic motifs that could replace the previously reported imidazo[1,2-a]pyridine or 1H-benzimidazole motif. The results indicated that the binding affinity of a chemically neutral 2H-indazole derivative 8a with MCHR1 (hMCHR1: IC50 = 35 nM) was comparable to that of the imidazopyridine and benzimidazole derivatives (1 and 2, respectively) reported so far. However, 8a was positive in the Ames test using TA1537 in S9- condition. Based on a putative intercalation of 8a with DNA, we introduced a sterically-hindering cyclopropyl group on the indazole ring to decrease planarity, which led to the discovery of 1-(2-cyclopropyl-3-methyl-2H-indazol- 5-yl)-4-[5-(trifluoromethyl)thiophen-3-yl]methoxy} pyridin-2(1H)-one 8l without mutagenicity in TA1537. Compound 8l exerted significant antiobesity effects in diet-induced obese F344 rats and exhibited promising safety profile. (C) 2016 Elsevier Ltd. All rights reserved.