1-(4-Aminophenyl)-3-methyl-3-azabicyclo[3.1.0]hexane-2,4-dione | 93579-64-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-Aminophenyl)-3-methyl-3-azabicyclo[3.1.0]hexane-2,4-dione
• CAS: 93579-64-7
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: VPRYTWJJTHHMAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-phenylcyclopropanedicarboxylic acid 在 palladium on activated charcoal 硫酸 、 氢气 、 硝酸 、 sodium hydride 、 尿素 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 37.0h， 生成 1-(4-Aminophenyl)-3-methyl-3-azabicyclo[3.1.0]hexane-2,4-dione
  参考文献：
  名称：

  基于1-苯基-3-氮杂双环[3.1.0]己烷-2,4-二酮的氨基谷氨酰胺的类似物：选择性抑制芳香化酶活性。

  摘要：

  在探索氨基谷氨酰胺[3-（4-氨基苯基）-3-乙基哌啶-2,6-二酮]（1）对牛肾上腺和人的胆固醇侧链裂解（CSCC）酶的抑制活性的结构特征时合成了胎盘芳香酶，其中哌啶-2，6-二酮环被取代或未取代的氮杂双环[3.1.0]己烷-2，4-二酮环取代。未取代的类似物1-（4-氨基苯基）-3-氮杂双环[3.1.0]己烷-2,4-二酮（9a）是一种比1更为有效的芳香化酶抑制剂（Ki = 1.2 microM，参见1.8 microM 1）但对CSCC酶无抑制作用。取代的类似物1-（4-氨基苯基）-3-丁基-3-氮杂双环[3.1.0]己烷-2,4-二酮（9e）和1-（4-氨基苯基）-3-戊基-3-氮杂双环[ 3.1.0]己烷-2，4-二酮（9f）在抑制芳香化酶方面的效力比1（Ki值分别为1、9e和9f分别为1.8、0.015和0.02 microM）高1倍，对CSCC酶没有明显的活性。II型差异谱在

  DOI：

  10.1021/jm00400a014

文献信息

• Substituted azabicycloalkanes, the use thereof, pharmaceutical
  申请人：Ciba-Geigy Corporation

  公开号：US04839379A1

  公开（公告）日：1989-06-13

  1-Phenyl-3-azabicyclo[3.1.0]hexane-2,4-diones of the formula ##STR1## wherein R.sub.1 is hydrogen, R.sub.2 is hydrogen, sulfo or acyl and R.sub.3 is hydrogen, or R.sub.1 is a saturated or unsaturated aliphatic, cycloaliphatic or cycloaliphatic-aliphatic carbon radical of up to and including 18, preferably of up to and including 12, carbon atoms, R.sub.2 is hydrogen, lower alkyl, sulfo or acyl and R.sub.3 is hydrogen or lower alkyl, and to salts thereof, and salts thereof, have valuable pharmacological properties and are effective aromatase inhibitors. They can therefore be used for the treatment of hormonal diseases, in particular mammary carcinomas.

  公式为##STR1##的1-苯基-3-氮杂双环[3.1.0]己烷-2,4-二酮，其中R.sub.1为氢，R.sub.2为氢、磺酰基或酰基，R.sub.3为氢，或者R.sub.1为饱和或不饱和的脂肪族、环状脂肪族或环状脂肪族-脂肪族碳基，碳原子数最多为18，优选最多为12，R.sub.2为氢、低碳烷基、磺酰基或酰基，R.sub.3为氢或低碳烷基，以及其盐，具有有价值的药理学特性，并且是有效的芳香化酶抑制剂。因此，它们可用于治疗激素疾病，特别是乳腺癌。
• 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。
• 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。
• Pharmaceutical composition comprisng an aromatase inhibitor and an estrogen suitable for hormone replacement therapy for a male
  申请人：——

  公开号：US20040235812A1

  公开（公告）日：2004-11-25

  A pharmaceutical preparation for males for increasing physiologic endogenous testosterone comprising at least one aromatase inhbitor and an estrogen and methods of use thereof for increasing male libido are provided.

  本研究提供了一种用于增加男性生理性内源性睾酮的药物制剂，该制剂包含至少一种芳香化酶抑制剂和一种雌激素，并提供了增加男性性欲的使用方法。
• Combination of an aromatase inhibitor with a bisphosphonate
  申请人：Bhatnagar S Ajay

  公开号：US20060069067A1

  公开（公告）日：2006-03-30

  The present invention provides a combination for the treatment of a disease or condition which responds to aromatase inhibition, in particular a proliferative disease, especially a malignant disease such as breast cancer or similar soft tissue endocrine-sensitive cancer, most preferably breast cancer, comprising an aromatase inhibitor and a bisphosphonate for simultaneous, concurrent, separate or sequential use in the prevention of bone loss which is caused by the treatment with an aromatase inhibitor. Also provided is a method of treating a patient suffering from a disease or condition which responds to aromatase inhibition comprising administering to the patient an effective amount of a bisphosphonate and an effective amount of an aromatase inhibitor.

  本发明提供了一种组合物，用于治疗对芳香化酶抑制剂有反应的疾病或病症，特别是增殖性疾病，尤其是恶性疾病，如乳腺癌或类似的软组织内分泌敏感性癌症，最优选乳腺癌，该组合物包括芳香化酶抑制剂和双膦酸盐，用于同时、并发、单独或连续使用，以防止因芳香化酶抑制剂治疗而引起的骨质流失。还提供了一种治疗对芳香化酶抑制剂有反应的疾病或病症患者的方法，包括向患者施用有效量的双膦酸盐和有效量的芳香化酶抑制剂。