P-276-00 free base | 920113-02-6

• 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: P-276-00 free base
• 英文别名: 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2S,3R)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one
• CAS: 920113-02-6
• 化学式: C₂₁H₂₀ClNO₅
• 分子量: 401.8
• InChiKey: QLUYMIVVAYRECT-GXTWGEPZSA-N

物化性质

• 沸点：
  603.3±55.0 °C(Predicted)
• 密度：
  1.429±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  90.2
• 氢给体数：
  3
• 氢受体数：
  6

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。
• [EN] A PHARMACEUTICAL COMBINATION FOR THE TREATMENT OF MELANOMA<br/>[FR] COMBINAISON PHARMACEUTIQUE POUR LE TRAITEMENT DU MÉLANOME
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2015004636A1

  公开（公告）日：2015-01-15

  The present invention relates to a pharmaceutical combination comprising a cyclin dependent kinase (CDK) inhibitor represented by a compound of formula I (as described herein) or a pharmaceutically acceptable salt thereof; and at least one anticancer agent selected from a BRAF inhibitor or a MEK inhibitor, for use in the treatment of melanoma. The present invention also relates to a method for the treatment of melanoma comprising administering to a subject in need thereof, a therapeutically effective amount of a CDK inhibitor and a therapeutically effective amount of at least one anticancer agent selected from a BRAF inhibitor or a MEK inhibitor.

  本发明涉及一种制药组合物，包括一种由式I（如本文所述）的细胞周期蛋白依赖性激酶（CDK）抑制剂或其药学上可接受的盐所表示的CDK抑制剂；以及至少一种从BRAF抑制剂或MEK抑制剂中选择的抗癌剂，用于治疗黑色素瘤。本发明还涉及一种治疗黑色素瘤的方法，包括向需要该治疗的受试者投予治疗有效量的CDK抑制剂和至少一种从BRAF抑制剂或MEK抑制剂中选择的治疗有效量的抗癌剂。