(-)-trans-1-[2-hydroxy-3-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4,6-dimethoxyphenyl]-ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (-)-trans-1-[2-hydroxy-3-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4,6-dimethoxyphenyl]-ethanone
• 英文别名: (-)-trans-1-[2-hydroxy-3-(2-hydroxymethyl-1-methylpyrrolidin-3-yl)-4,6-dimethoxyphenyl]ethanone；(-)-trans-1-[2-Hydroxy-3-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4,6-dimethoxyphenyl]-1-ethanone；1-[2-hydroxy-3-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]-4,6-dimethoxyphenyl]ethanone
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: JJSDPGSJXCYILH-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-trans-1-[2-hydroxy-3-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4,6-dimethoxyphenyl]-ethanone 在 吡啶盐酸盐 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.67h， 生成 (+)-trans-2-(2-chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one
  参考文献：
  名称：

  [EN] SOLID ORAL FORMULATION OF A PYRROLIDINE SUBSTITUTED FLAVONE COMPOUND
  [FR] FORMULATION ORALE SOLIDE D'UN COMPOSÉ DE FLAVONE SUBSTITUÉ PAR PYRROLIDINE

  摘要：

  本发明涉及一种药物组合物，提供一种自乳化药物输送系统(SEDDS)用于口服给药，包括化合物(+)-trans-2-(2-氯苯基)-5,7-二羟基-8-(2-羟甲基-1-甲基-吡咯烷-3-基)-香豆素-4-酮或其药学上可接受的盐，以及一种或多种表面活性剂和一种溶解剂。本发明还涉及一种制备所述药物组合物的方法，以及将药物组合物用于治疗癌症、多囊肾病、肾病学疾病、牛皮癣、涉及白细胞不必要增殖的免疫学疾病、再狭窄、增生性平滑肌疾病、放射性黏膜炎、病毒感染、真菌感染或心血管异常的疾病或紊乱的用途。

  公开号：

  WO2014140695A1
• 作为产物：
  描述：

  2-吡咯烷甲醇,1-甲基-3-(2,4,6-三甲氧苯基)-,(2R,3S)-rel- 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-1-[2-hydroxy-3-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-4,6-dimethoxyphenyl]-ethanone
  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] CYTOKINE INHIBITORS<br/>[FR] INHIBITEURS DE CYTOKINE
  申请人：PIRAMAL LIFE SCIENCES LTD

  公开号：WO2011121505A1

  公开（公告）日：2011-10-06

  The present invention provides compounds represented by general formula (I): wherein, R1; R2, R3, L and T are as defined in the specification, in all their stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, and prodrugs thereof. The invention also relates to processes for the manufacture of compounds of formula (I) and pharmaceutical compositions containing them. The compounds and the pharmaceutical compositions of the present invention are useful in the treatment of a condition or disorder mediated by one or more cytokines selected from Tumor Necrosis Factor-alpha (TNF-oc) and interleukins such as IL-1, IL-6, and IL-8. The present invention further provides a method of treatment of inflammatory disorders by administering a therapeutically effective amount of the said compound of formula (I) or its pharmaceutical composition, to a mammal in need thereof.

  本发明提供了由通式（I）表示的化合物：其中，R1；R2，R3，L和T如规范中定义的，在它们的所有立体异构体和互变异构体形式及其各种比例的混合物中，以及它们的药学上可接受的盐、药学上可接受的溶剂化合物和其前药。本发明还涉及制备通式（I）化合物的方法和含有它们的药物组合物的制备方法。本发明的化合物和药物组合物在治疗由肿瘤坏死因子-α（TNF-oc）和白细胞介素（如IL-1、IL-6和IL-8）中选择的一个或多个细胞因子介导的疾病或紊乱方面是有用的。本发明进一步提供了一种通过向需要的哺乳动物体内给予通式（I）的所述化合物或其药物组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。
• 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。
• INHIBITORS OF CYCLIN DEPENDENT KINASES AND THEIR USE
  申请人：Lal Bansi

  公开号：US20070015802A1

  公开（公告）日：2007-01-18

  The present invention relates to novel compounds for the inhibition of cyclin-dependent kinases, and more particularly, to chromenone derivatives of formula (Ic) 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 (Ic) 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 (Ic) in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula (Ic) 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 (Ic) 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，特别是公式(Ic)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抑制细胞增殖的方法，以及使用公式(Ic)化合物在治疗和预防细胞周期蛋白依赖性激酶抑制剂可治疗或预防的疾病，如癌症，以及使用公式(Ic)化合物制备应用于这些疾病的药物。本发明还涉及含有公式(Ic)化合物的组合物，单独或与另一种活性剂联合使用，与惰性载体混合或以其他方式与惰性载体相结合，特别是含有公式(Ic)化合物的药物组合物，单独或与另一种活性剂联合使用，以及与药用载体物质和辅助物质相结合。