(+)-trans-2-(2-Chloro-4-nitrophenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one | 1242983-26-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: (+)-trans-2-(2-Chloro-4-nitrophenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one
• 英文别名: 2-(2-Chloro-4-nitrophenyl)-8-[2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]-5,7-dimethoxychromen-4-one
• CAS: 1242983-26-1
• 化学式: C₂₃H₂₃ClN₂O₇
• 分子量: 474.898
• InChiKey: GHMBWGANDSDIRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (+)-trans-2-(2-Chloro-4-nitrophenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以48%的产率得到2-[5-(2-chloro-4-nitro-phenyl)-1H-pyrazol-3-yl]-6-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-3,5-dimethoxyphenol
  参考文献：
  名称：

  Synthesis of novel 3,5-diaryl pyrazole derivatives using combinatorial chemistry as inhibitors of tyrosinase as well as potent anticancer, anti-inflammatory agents

  摘要：

  In the present article, we have synthesized a combinatorial library of 3,5-diaryl pyrazole derivatives using 8-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (1) and hydrazine hydrate in absolute ethyl alcohol under the refluxed conditions. The structures of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their anticancer activity against five cell lines (breast cancer cell line, prostate cancer cell line, promyelocytic leukemia cell line, lung cancer cell line, colon cancer cell line) and anti-inflammatory activity against TNF-alpha and IL-6. Out of 15 compounds screened, 2a and 2d exhibited promising anticancer activity (61-73% at 10 mu M concentration) against all selected cell lines and IL-6 inhibition (47% and 42% at 10 mu M concentration) as in comparison to standard flavopiridol (72-87% inhibition at 0.5 mu M) and dexamethasone (85% inhibition at 1 mu M concentration), respectively. Cytotoxicity of the compounds checked using CCK-8 cell lines and found to be nontoxic to slightly toxic. Out of 15, four 3,5-diaryl pyrazole derivatives exhibiting potent inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase. The IC(50) values of compounds (2a, 2d, 2h and 21) for monophenolase inhibition were determined to range between 1.5 and 30 mu M. Compounds 2a, 2d, 2h and 21 also inhibited diphenolase significantly with IC(50) values of 29.4, 21.5, 2.84 and 19.6 mu M, respectively. All four 3,5-diaryl pyrazole derivatives were active as tyrosinase inhibitors (2a, 2d, 2h and 21), and belonging to competitive inhibitors. Interestingly, they all manifested simple reversible slow-binding inhibition against diphenolase. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.06.046
• 作为产物：
  描述：

  1,2,3,6-四氢-1-甲基-4-(2,4,6-三甲氧基苯基)-吡啶 在 盐酸 、 甲醇 、 sodium hydroxide 、 sodium tetrahydroborate 、 三氟化硼乙醚 、 水 、 sodium hydride 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 35.92h， 生成 (+)-trans-2-(2-Chloro-4-nitrophenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one
  参考文献：
  名称：

  WO2007/148158

  摘要：

  公开号：

文献信息

• NOVEL ENANTIOMERICALLY PURE COMPOUNDS FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Sivakumar Meenakshi

  公开号：US20100179210A1

  公开（公告）日：2010-07-15

  The present invention relates to an enantiomerically pure (+)-trans-enantiomer of a compound represented by the following formula (I): wherein R 1 , R 2 , R 3 , R 4 and R 9 are as defined in the specification; enantiomerically pure intermediates thereof, to processes for the preparation of the enantiomerically pure compound and its intermediates, and to a pharmaceutical composition comprising the enantiomerically pure compound. The compound of formula (I) is useful for the treatment of diseases or disorders mediated by the inhibition of cyclin dependant kinase, such as cancer.

  本发明涉及一种由以下式（I）表示的化合物的对映纯（+）-反式对映体：其中R1、R2、R3、R4和R9如规范中定义；其对映纯中间体；制备对映纯化合物及其中间体的方法；以及包含对映纯化合物的药物组合物。式（I）的化合物对于治疗由细胞周期依赖性激酶抑制介导的疾病或紊乱，如癌症，是有用的。
• ENANTIOMERICALLY PURE FLAVONE DERIVATIVES FOR THE TREATMENT OF POLIFERATIVE DISORDERS AND PROCESSES FOR THEIR PREPARATION
  申请人：Piramal Life Sciences Limited

  公开号：EP2046738A1

  公开（公告）日：2009-04-15
• ENANTIOMERICALLY PURE FLAVONE DERIVATIVES FOR THE TREATMENT OF PROLIFERATIVE DISORDERS AND PROCESSES FOR THEIR PREPARATION
  申请人：Piramal Enterprises Limited

  公开号：EP2046738B1

  公开（公告）日：2014-06-11
• US8563596B2
  申请人：——

  公开号：US8563596B2

  公开（公告）日：2013-10-22
• [EN] ENANTIOMERICALLY PURE FLAVONE DERIVATIVES FOR THE TREATMENT OF POLIFERATIVE DISORDERS AND PROCESSES FOR THEIR PREPARATION<br/>[FR] DÉRIVÉS DE FLAVONE ENANTIOMÉRIQUEMENT PURS POUR LE TRAITEMENT DE TROUBLES POLIFÉRATIFS ET LEURS PROCÉDÉS DE PRÉPARATION
  申请人：NICHOLAS PIRAMAL INDIA LTD

  公开号：WO2007148158A1

  公开（公告）日：2007-12-27

  [EN] The present invention relates to an enantiomerically pure (+)-trans-enantiomer of a compound represented by the following formula (I): wherein R₁, R₂, R₃, R₄ and R₉ are as defined in the specification; enantiomerically pure intermediates thereof, to processes for the preparation of the enantiomerically pure compound and its intermediates, and to a pharmaceutical composition comprising the enantiomerically pure compound. The compound of formula (I) is useful for the treatment of diseases or disorders mediated by the inhibition of cyclin dependant kinase, such as cancer.
  [FR] La présente invention concerne un énantiomère (+)- trans énantiomériquement pur représenté par la formule suivante (I): R₁, R₂, R₃, R₄ et R₉ étant tels que définis dans la description; l'invention concerne aussi des intermédiaires énantiomériquement purs de celui-ci, des procédés de préparation du composé énantiomériquement pur et de ses intermédiaires, ainsi qu'une composition pharmaceutique comprenant le composé énantiomériquement pur. Le composé de formule (I) est utile pour le traitement de maladies ou de troubles associés à l'inhibition de la kinase cycline-dépendante, tel le cancer.