((-)-trans-acetic acid-3-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methylpyrrolidin-2-yl)methyl ester | 920112-99-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ((-)-trans-acetic acid-3-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methylpyrrolidin-2-yl)methyl ester
• 英文别名: (-)-trans-acetic acid 3-(3-acetyl-2-hydroxy-4,6-dimethoxy-phenyl)-1-methyl-pyrrolidin-2-yl methyl ester；(+/-)-trans-Acetic acid 3-(3-acetyl-2-hydroxy-4,6-dimethoxy-phenyl)-1-methyl-pyrrolidin-2-ylmethyl ester；[(2R,3S)-3-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methylpyrrolidin-2-yl]methyl acetate
• CAS: 920112-99-8
• 化学式: C₁₈H₂₅NO₆
• 分子量: 351.4
• InChiKey: RIYGVWPZTGPGKT-OLZOCXBDSA-N

物化性质

• 沸点：
  447.5±45.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ((-)-trans-acetic acid-3-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methylpyrrolidin-2-yl)methyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.75h， 以81.1%的产率得到(-)-trans-1-[2-hydroxy-3-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4,6-dimethoxyphenyl]-ethanone
  参考文献：
  名称：

  WO2008/7169

  摘要：

  公开号：
• 作为产物：
  描述：

  (±)-trans-1-methyl-3-(2,4,6-trimethoxyphenyl)pyrrolidin-2-yl acetic acid methyl ester 在 三氟化硼乙醚 、 水 、 sodium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 乙酸酐 、 乙酸乙酯 为溶剂， 反应 5.92h， 生成 ((-)-trans-acetic acid-3-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methylpyrrolidin-2-yl)methyl ester
  参考文献：
  名称：

  PYRROLIDINE-SUBSTITUTED FLAVONES AS RADIO-SENSITIZERS FOR USE IN THE TREATMENT OF CANCER

  摘要：

  公开号：

  EP2427188B1

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。
• [EN] AN IMPROVED PROCESS FOR PREPARATION OF AN INTERMEDIATE OF THE PYRROLIDINE SUBSTITUTED FLAVONES<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION D'UN INTERMÉDIAIRE DE FLAVONES SUBSTITUÉES PAR PYRROLIDINE
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2014128524A1

  公开（公告）日：2014-08-28

  The present invention relates to a process for the preparation of a key intermediate (as described herein) used in the synthesis of (+)-trans enantiomer of pyrrolidine substituted flavones, represented by the compounds of formula (1) or pharmaceutically acceptable salts thereof; which are inhibitors of cyclin dependant kinases (CDKs) and can be used in the treatment of proliferative disorders such as cancer. Formula (1) wherein R1 has the meaning as indicated in the claims. The process of the present invention has advantages of higher yield and purity, lower reaction temperature, is consistent and involves the use of non toxic solvents. The process of the present invention allows efficient large-scale synthesis and purity of the product obtained is greater than 97 %.

  本发明涉及一种用于制备一种关键中间体（如本文所述）的过程，该中间体用于合成嘧啶取代黄酮类化合物的（+）-反式对映体，该化合物由式（1）所表示，或其药学上可接受的盐；这些化合物是细胞周期依赖性激酶（CDKs）的抑制剂，可用于治疗癌症等增殖性疾病。式（1）中R1的含义如索引中所示。本发明的过程具有较高的产率和纯度优势，反应温度较低，一致性好，并且使用无毒溶剂。本发明的过程允许高效的大规模合成，所得产品的纯度大于97%。
• [EN] A PROCESS FOR PREPARATION OF AN INTERMEDIATE OF THE PYRROLIDINE SUBSTITUTED FLAVONES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN INTERMÉDIAIRE DE FLAVONES SUBSTITUÉES PAR UNE PYRROLIDINE
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2014128523A1

  公开（公告）日：2014-08-28

  The present invention relates to a process for the preparation of a key intermediate (as described herein) used in the synthesis of (+)-trans enantiomer of pyrrolidine substituted flavones, represented by the compounds of formula (1) or pharmaceutically acceptable salts thereof; which are inhibitors of cyclin dependant kinases (CDKs) and can be used in the treatment of proliferative disorders such as cancer. Formula (1) wherein R has the meaning as indicated in the claims. The process of the present invention has advantages of higher yield and purity, lower reaction temperature, is consistent and involves the use of non toxic solvents. The process of the present invention allows efficient large-scale synthesis and purity of the product obtained is greater than 97 %.

  本发明涉及一种用于制备一种关键中间体（如本文所述）的方法，该中间体用于合成嘧啶基取代的黄酮类化合物的（+）-反式对映体，该化合物由式（1）所代表，或其药学上可接受的盐；这些化合物是细胞周期依赖性激酶（CDKs）的抑制剂，可用于治疗癌症等增殖性疾病。式（1）中R的含义如索权中所示。本发明的方法具有较高的产率和纯度优势，反应温度较低，稳定且使用无毒溶剂。本发明的方法允许高效的大规模合成，所得产品的纯度大于97％。
• [EN] PYRROLIDINE SUBSTITUTED FLAVONES FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] FLAVONES À SUBSTITUTION PYRROLIDINE POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：PIRAMAL LIFE SCIENCES LTD

  公开号：WO2011104584A1

  公开（公告）日：2011-09-01

  The present invention relates to the use of a compound of formula 1, a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, for the treatment of an inflammatory disorder. The invention further relates to a pharmaceutical composition comprising a compound of formula 1 and at least one pharmaceutically acceptable carrier, for use in the treatment of an inflammatory disorder. The invention also relates to a method for the treatment of an inflammatory disorder by administering a therapeutically effective amount of the compound of formula 1 to a subject in need thereof.

  本发明涉及使用式1的化合物，其立体异构体或互变异构体，或其药学上可接受的盐或药学上可接受的溶剂，用于治疗炎症性疾病。该发明还涉及包含式1化合物和至少一种药学上可接受的载体的药物组合物，用于治疗炎症性疾病。该发明还涉及通过向需要的受试者施用式1化合物的治疗有效量来治疗炎症性疾病的方法。
• Inhibitors of cyclin-dependent kinases and their use
  申请人：——

  公开号：US20040106581A1

  公开（公告）日：2004-06-03

  The present invention relates to novel compounds for the inhibition of cyclin-dependent kinases, and more particularly, to chromenone derivatives of formula (Ia), 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and A have the meanings indicated in the claims. The invention also relates to processes for the preparation of the compounds of formula (Ia), to methods of inhibiting cyclin-dependent kinases and of inhibiting cell proliferation, to the use of the compounds of formula (Ia) in the treatment and prophylaxis of diseases, which can be treated or prevented by the inhibition of cyclin-dependent kinases such as cancer, to the use of the compounds of formula (Ia) in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula (Ia) either alone or in combination with another active agent, in admixture or otherwise in association with an inert carrier, in particular pharmaceutical compositions containing a compound of formula (Ia) either alone or in combination with another active agent, together with pharmaceutically acceptable carrier substances and auxiliary substances.

  本发明涉及一种新型化合物，用于抑制细胞周期蛋白依赖性激酶，尤其是公式（Ia）的香豆素衍生物，其中R1、R2、R3、R4、R5、R6、R7和A的含义如权利要求中所示。本发明还涉及制备公式（Ia）化合物的方法，抑制细胞周期蛋白依赖性激酶和细胞增殖的方法，使用公式（Ia）化合物治疗和预防由于细胞周期蛋白依赖性激酶抑制而可以治疗或预防的疾病，如癌症，使用公式（Ia）化合物制备用于治疗此类疾病的药物。本发明还涉及含有公式（Ia）化合物的组合物，单独或与另一活性剂结合，与惰性载体混合或以其他方式结合，特别是含有公式（Ia）化合物的药物组合物，单独或与另一活性剂结合，与药用可接受载体物质和辅助物质一起使用的制剂。