methyl 3-nitro-2-{[(trifluoromethyl)sulfonyl]oxy}benzoate | 521074-26-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-nitro-2-{[(trifluoromethyl)sulfonyl]oxy}benzoate
• 英文别名: Methyl 3-nitro-2-(trifluoromethylsulfonyloxy)benzoate
• CAS: 521074-26-0
• 化学式: C₉H₆F₃NO₇S
• 分子量: 329.21
• InChiKey: XZUVQYUQZMXYJL-UHFFFAOYSA-N

物化性质

• 沸点：
  407.2±45.0 °C(Predicted)
• 密度：
  1.641±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 3-nitro-2-{[(trifluoromethyl)sulfonyl]oxy}benzoate 在 盐酸 、 四(三苯基膦)钯 、 叠氮磷酸二苯酯 、 5%-palladium/activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 溶剂黄146 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 61.0h， 生成 N-(3-amino-2-ethylphenyl)-4-bromobenzamide
  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：

  N-苯基双(三氟甲烷磺酰)亚胺 、 3-硝基水杨酸甲酯 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 生成 methyl 3-nitro-2-{[(trifluoromethyl)sulfonyl]oxy}benzoate
  参考文献：
  名称：

  EP1447402

  摘要：

  公开号：

文献信息

• A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced-Fit Pocket Stabilized by a Cation-π Interaction
  作者：Timothy P. C. Rooney、Panagis Filippakopoulos、Oleg Fedorov、Sarah Picaud、Wilian A. Cortopassi、Duncan A. Hay、Sarah Martin、Anthony Tumber、Catherine M. Rogers、Martin Philpott、Minghua Wang、Amber L. Thompson、Tom D. Heightman、David C. Pryde、Andrew Cook、Robert S. Paton、Susanne Müller、Stefan Knapp、Paul E. Brennan、Stuart J. Conway

  DOI：10.1002/anie.201402750

  日期：2014.6.10

  development of CREBBP bromodomain ligands. While the benzoxazinone series showed low affinity for the CREBBP bromodomain, expansion of the dihydroquinoxalinone series resulted in the first potent inhibitors of a bromodomain outside the BET family. Structural and computational studies reveal that an internal hydrogen bond stabilizes the protein‐bound conformation of the dihydroquinoxalinone series. The side

  在 CREBBP 溴结构域配体的开发中，苯并嗪酮和二氢喹喔啉酮片段被用作新型乙酰赖氨酸模拟物。虽然苯并嗪酮系列对 CREBBP 溴结构域显示出低亲和力，但二氢喹喔啉酮系列的扩展导致了 BET 家族之外溴结构域的第一个有效抑制剂。结构和计算研究表明，内部氢键稳定了二氢喹喔啉酮系列的蛋白质结合构象。该系列的侧链结合在诱导拟合口袋中，与 CREBBP 的 R1173 形成阳离子-π 相互作用。最有效的化合物抑制 CREBBP 与 U2OS 细胞中染色质的结合。
• 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.