4-bromo-N-(3-formyl-6-methyl-7-quinolinyl)benzamide | 521074-43-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-bromo-N-(3-formyl-6-methyl-7-quinolinyl)benzamide
• 英文别名: 4-bromo-N-(3-formyl-6-methylquinolin-7-yl)benzamide
• CAS: 521074-43-1
• 化学式: C₁₈H₁₃BrN₂O₂
• 分子量: 369.217
• InChiKey: MXBOBGDPPFSHTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-bromo-N-(3-formyl-6-methyl-7-quinolinyl)benzamide 在 盐酸 、 sodium tetrahydroborate 、 氯化亚砜 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 8.0h， 生成 6-methyl-3-(1-pyrrolidinylmethyl)-7-quinolinamine hydrochloride
  参考文献：
  名称：

  Melanin-Concentrating Hormone Receptor 1 Antagonists. Synthesis and Structure–Activity Relationships of Novel 3-(Aminomethyl)quinolines

  摘要：

  It was found that 3-(aminomethyl)quinoline derivatives showed high binding affinities for melanin-concentrating hormone receptor 1 (MCHR1) with reduced affinity for serotonin receptor 2c (5-HT2c) when the dihydronaphthalene nucleus of compound 1 (human MCHR1, IC50 = 1.9 nM; human 5-HT2c receptor, IC50 = 0.53 nM) was replaced by other bicyclic core scaffolds. Among the synthesized compounds, 8-methylquinoline derivative 5v especially showed high binding affinity (IC50 = 0.54 nM), potent in vitro antagonistic activity (IC50 = 2.8 nM) for MCHR1, and negligible affinity for 5-HT2c receptor (IC50 > 1000 nM). Oral administration of 5v significantly and dose-dependently suppressed nocturnal food intake in diet-induced obese rats and did not affect food intake in MCHR1-deficient mice. These results and rat pharmacokinetic study findings suggested that compound 5v is a highly potent, orally bioavailable, and centrally acting nonpeptide MCHR1 antagonist.

  DOI：

  10.1021/jm201596h
• 作为产物：
  描述：

  4-bromo-N-(2-methyl-5-nitrophenyl)benzamide 在 铁粉 、 calcium chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 32.0h， 生成 4-bromo-N-(3-formyl-6-methyl-7-quinolinyl)benzamide
  参考文献：
  名称：

  Melanin-Concentrating Hormone Receptor 1 Antagonists. Synthesis and Structure–Activity Relationships of Novel 3-(Aminomethyl)quinolines

  摘要：

  It was found that 3-(aminomethyl)quinoline derivatives showed high binding affinities for melanin-concentrating hormone receptor 1 (MCHR1) with reduced affinity for serotonin receptor 2c (5-HT2c) when the dihydronaphthalene nucleus of compound 1 (human MCHR1, IC50 = 1.9 nM; human 5-HT2c receptor, IC50 = 0.53 nM) was replaced by other bicyclic core scaffolds. Among the synthesized compounds, 8-methylquinoline derivative 5v especially showed high binding affinity (IC50 = 0.54 nM), potent in vitro antagonistic activity (IC50 = 2.8 nM) for MCHR1, and negligible affinity for 5-HT2c receptor (IC50 > 1000 nM). Oral administration of 5v significantly and dose-dependently suppressed nocturnal food intake in diet-induced obese rats and did not affect food intake in MCHR1-deficient mice. These results and rat pharmacokinetic study findings suggested that compound 5v is a highly potent, orally bioavailable, and centrally acting nonpeptide MCHR1 antagonist.

  DOI：

  10.1021/jm201596h

文献信息

• Quinoline compound
  申请人：Ishihara Yuji

  公开号：US20050209213A1

  公开（公告）日：2005-09-22

  A compound, which has a melanin-concentrating hormone antagonistic action and useful as an agent for preventing or treating obesity, and which is represented by the formula: wherein Ar is a cyclic group optionally having substituent(s); X is a bond or a spacer having a main chain of 1 to 6 atoms; R 1 and R 2 are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R 1 and R 2 may form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent(s); Y is a divalent hydrocarbon group optionally having substituent(s) (except CO); R 3 is a hydrogen atom or a hydrocarbon group optionally having substituent(s); and ring A and ring B may further have substituents, and when ring B further has a substituent, the substituent may be linked to R 1 to form a ring, or a salt thereof, or a prodrug thereof, is provided.

  一种化合物，具有黑色素浓缩激素拮抗作用，可用作预防或治疗肥胖症的药物，其化学式为：其中，Ar是一个环状基团，可以有取代基；X是1到6个原子的主链的键或空隙；R1和R2相同或不同，分别是氢原子或烃基，可以有取代基，或者R1和R2可以与相邻的氮原子一起形成含氮杂环，可以有取代基；Y是一个双价的烃基，可以有取代基（除CO）；R3是氢原子或烃基，可以有取代基；环A和环B还可以有取代基，当环B还有取代基时，取代基可以与R1连接形成一个环，或其盐，或其前药。
• QUINOLINE COMPOUND
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1447402A1

  公开（公告）日：2004-08-18

  A compound, which has a melanin-concentrating hormone antagonistic action and useful as an agent for preventing or treating obesity, and which is represented by the formula:    wherein Aris a cyclic group optionally having substituent(s) ; Xis a bond or a spacer having a main chain of 1 to 6 atoms; R1 and R2are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R1 and R2 may form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent(s); Yis a divalent hydrocarbon group optionally having substituent(s) (except CO); R3is a hydrogen atom or a hydrocarbon group optionally having substituent(s); and ring A and ring Bmay further have substituents, and when ring B further has a substituent, the substituent may be linked to R1 to form a ring, or a salt thereof, or a prodrug thereof, is provided.

  一种化合物，具有拮抗黑色素浓缩激素的作用，可作为预防或治疗肥胖症的药物，由式表示： 式中 Ar 是一个环状基团，可选择具有取代基； X 是主链为 1 至 6 个原子的键或间隔物； R1 和 R2 相同或不同，各自为氢原子或任选具有取代基的烃基，或 R1 和 R2 可与邻近的氮原子一起形成任选具有取代基的含氮杂环； Y 是可选具有取代基的二价烃基（CO 除外）； R3 是氢原子或可选具有取代基的烃基；以及 环 A 和环 B 可进一步具有取代基，当环 B 进一步具有取代基时，该取代基可与 R1 连接形成一个环、 或其盐或其原药。
• US7183415B2
  申请人：——

  公开号：US7183415B2

  公开（公告）日：2007-02-27
• Melanin-Concentrating Hormone Receptor 1 Antagonists. Synthesis and Structure–Activity Relationships of Novel 3-(Aminomethyl)quinolines
  作者：Makoto Kamata、Toshiro Yamashita、Toshihiro Imaeda、Toshio Tanaka、Shinichi Masada、Masahiro Kamaura、Shizuo Kasai、Ryoma Hara、Shigekazu Sasaki、Shiro Takekawa、Asano Asami、Tomoko Kaisho、Nobuhiro Suzuki、Shuntaro Ashina、Hitomi Ogino、Yoshihide Nakano、Yasutaka Nagisa、Koki Kato、Kaneyoshi Kato、Yuji Ishihara

  DOI：10.1021/jm201596h

  日期：2012.3.8

  It was found that 3-(aminomethyl)quinoline derivatives showed high binding affinities for melanin-concentrating hormone receptor 1 (MCHR1) with reduced affinity for serotonin receptor 2c (5-HT2c) when the dihydronaphthalene nucleus of compound 1 (human MCHR1, IC50 = 1.9 nM; human 5-HT2c receptor, IC50 = 0.53 nM) was replaced by other bicyclic core scaffolds. Among the synthesized compounds, 8-methylquinoline derivative 5v especially showed high binding affinity (IC50 = 0.54 nM), potent in vitro antagonistic activity (IC50 = 2.8 nM) for MCHR1, and negligible affinity for 5-HT2c receptor (IC50 > 1000 nM). Oral administration of 5v significantly and dose-dependently suppressed nocturnal food intake in diet-induced obese rats and did not affect food intake in MCHR1-deficient mice. These results and rat pharmacokinetic study findings suggested that compound 5v is a highly potent, orally bioavailable, and centrally acting nonpeptide MCHR1 antagonist.