5-((1H-imidazol-1-yl)methyl)indan-1-one | 132449-04-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-((1H-imidazol-1-yl)methyl)indan-1-one
• 英文别名: 5-(1H-imidazol-1-ylmethyl)-1-indanone；5-(1-imidazolylmethyl)-1-indanone；5-(Imidazol-1-ylmethyl)-2,3-dihydroinden-1-one
• CAS: 132449-04-8
• 化学式: C₁₃H₁₂N₂O
• 分子量: 212.251
• InChiKey: OOZNVXOYRBTUDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-((1H-imidazol-1-yl)methyl)indan-1-one 在 sodium hydride 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 苯 为溶剂， 生成 6-(Imidazol-1-ylmethyl)-3-[5-(3-phenoxyprop-1-ynyl)thiophen-3-yl]-1,4-dihydroindeno[1,2-c]pyrazole
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o
• 作为产物：
  描述：

  5-溴茚酮 在 sodium tetrahydroborate 、 正丁基锂 、 potassium carbonate 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 丙酮 、 苯 为溶剂， 生成 5-((1H-imidazol-1-yl)methyl)indan-1-one
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o

文献信息

• [EN] TRICYCLIC PYRAZOLE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES A BASE DE TYRAZOLES TRICYCLIQUES
  申请人：ABBOTT LAB

  公开号：WO2005095387A1

  公开（公告）日：2005-10-13

  Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  本发明的化合物对抑制蛋白酪氨酸激酶具有用处。还公开了制备这些化合物的方法、含有这些化合物的组合物以及使用这些化合物进行治疗的方法。
• Tricyclic pyrazole kinase inhibitors
  申请人：Arnold D. Lee

  公开号：US20060014816A1

  公开（公告）日：2006-01-19

  Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  本发明的化合物可用于抑制蛋白酪氨酸激酶。还公开了制备该化合物的方法，含有该化合物的组合物，以及使用该化合物的治疗方法。
• Aromatase inhibition to enhance assisted reproduction
  申请人：ARES TRADING S.A.

  公开号：EP1759734A2

  公开（公告）日：2007-03-07

  The use of at least one aromatase inhibitor in the production of a medicament for improving the implantation and pregnancy rates for a female undergoing assisted reproduction treatment, which comprises one or more daily doses of an aromatase inhibitor (Al) for administration during assisted reproduction cycles or ovarian stimulation cycles, wherein the doses of AI are selected from amounts effective to reduce serum estradiol levels. Also disclosed are related pharmaceutical preparations and packages.

  使用至少一种芳香化酶抑制剂生产一种药物，用于提高接受辅助生殖治疗的女性的着床率和妊娠率，该药物包括一种或多种每日剂量的芳香化酶抑制剂（Al），用于在辅助生殖周期或卵巢刺激周期期间给药，其中AI的剂量选自有效降低血清雌二醇水平的量。还公开了相关的药物制剂和包装。
• Single dose aromatase inhibitor for treating infertility
  申请人：——

  公开号：US20040171660A1

  公开（公告）日：2004-09-02

  The use of an aromatase inhibitor (AI) in the preparation of a medicament for use in inducing ovulation in a female suffering from anovulatory infertility which comprises administering to said female a single dose of the at least one aromatase inhibitor. The use of an aromatase inhibitor (AI) for the preparation of a medicament comprising a single dose of at least one aromatase inhibitor (AI) for administration to an ovulating female suffering from unexplained infertility or other types of ovulatory infertility early in one or more menstrual cycles. Such a medicament may also be administered to an anovulatory female in combination with a plurality of daily doses of follicle stimulating hormone (FSH) whereby the dosage levels of FSH may be reduced. The use of AI in the preparation of a medicament for administration to a female who is a poor responder to FSH, which comprises a combination of a single dose of AI with a plurality of daily doses of FSH is also disclosed. The related pharmaceutical preparations and packages are also described.

  芳香化酶抑制剂(AI)在制备用于诱导患有无排卵性不孕症的女性排卵的药物中的用途，包括向所述女性施用单剂量的至少一种芳香化酶抑制剂。芳香化酶抑制剂(AI)的用途，用于制备一种包含单剂量至少一种芳香化酶抑制剂(AI)的药剂，给患有不明原因不孕症或其他类型排卵性不孕症的排卵期女性在一个或多个月经周期的早期给药。这种药物也可与多种每日剂量的促卵泡激素（FSH）联合用于无排卵女性，从而降低促卵泡激素的剂量水平。此外，还公开了 AI 在制备用于对 FSH 反应不佳的女性的药物中的用途，该药物包括单剂量 AI 与多剂量每日 FSH 的组合。还描述了相关的药物制剂和包装。
• Multiple dose aromatase inhibitor for treating infertility
  申请人：——

  公开号：US20040235804A1

  公开（公告）日：2004-11-25

  A method of inducing ovulation in a female suffering from anovulatory infertility which comprises administering to said female two or more daily doses of at least one aromatase inhibitor. A method for augmenting ovulation in an ovulating female suffering from unexplained infertility or another type of ovulatory infertility which comprises administering to said female two or more daily doses of at least one aromatase inhibitor early in one or more menstrual cycles. A method of substantially reducing dosage levels of follicle stimulating hormone (FSH) for administration to a female undergoing infertility treatment which comprises administering a combination of two or more daily doses of at least one aromatase inhibitor (AI) with a plurality of daily doses of follicle stimulating hormone (FSH). A method of increasing response to a follicle stimulating hormone from a female who is a poor responder to follicle stimulation, which comprises administering a combination of two or more daily doses or at least one aromatase inhibitor (AI) with a plurality of daily doses of follicle stimulating hormone (FSH). Also disclosed are related pharmaceutical preparations and uses.

  一种诱导无排卵性不孕症女性排卵的方法，包括向所述女性施用两种或两种以上每日剂量的至少一种芳香化酶抑制剂。一种促进患有不明原因不孕症或另一种排卵性不孕症的女性排卵的方法，包括在一个或多个月经周期的早期给所述女性服用两个或多个每日剂量的至少一种芳香化酶抑制剂。一种大幅降低促卵泡激素(FSH)剂量水平的方法，用于对接受不孕治疗的女性用药，该方法包括将两种或两种以上日剂量的至少一种芳香化酶抑制剂(AI)与多种日剂量的促卵泡激素(FSH)联合用药。一种增加对卵泡刺激反应差的女性对卵泡刺激激素的反应的方法，它包括给药两种或两种以上每日剂量或至少一种芳香化酶抑制剂（AI）与多种每日剂量的卵泡刺激激素（FSH）的组合。还公开了相关的药物制剂和用途。