2-(azidomethyl)-N,N-diethyl-1-(4-hydroxyphenyl)cyclopropane-1-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(azidomethyl)-N,N-diethyl-1-(4-hydroxyphenyl)cyclopropane-1-carboxamide
• 化学式: C15H20N4O2
• 分子量: 288.34
• InChiKey: LDROUHSNTSSWML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  4

文献信息

• Stereoisomers of p-hydroxy-milnacipran, and methods of use thereof
  申请人：——

  公开号：US20040142904A1

  公开（公告）日：2004-07-22

  The present invention relates generally to the enantiomers of para-hydroxy-milnacipran or congeners thereof. Biological assays revealed that racemic para-hydroxy-milnacipran is approximately equipotent in inhibiting serotonin and norepinephrine uptake (IC 50 =28.6 nM for norepinephrine, IC 50 =21.7 nM for serotonin). Interestingly, (+)-para-hydroxy-milnacipran is a more potent inhibitor of norepinephrine uptake than serotonin uptake (IC 50 =10.3 nM for norepinephrine, IC 50 =22 nM for serotonin). In contrast, (−)-para-hydroxy-milnacipran is a more potent inhibitor of serotonin uptake compared to norepinephrin uptake (IC 50 =88.5 nM for norepinephrine, IC 50 =40.3 nM for serotonin). The invention also relates to salts and prodrug forms of the aforementioned compounds. In certain embodiments, the compounds of the present invention and a pharmaceutically acceptable excipient are combined to prepare a formulation for administration to a patient. Finally, the present invention relates to methods of treating mammals suffering from various afflictions, e.g., depression, chronic pain, or fibromyalgia, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of the present invention.

  本发明一般涉及对羟基米那西普兰的对映体或其同系物。生物学测定显示，外消旋对羟基米那西普兰在抑制血清素和去甲肾上腺素摄取方面具有近似等效的作用（IC 50 等于；去甲肾上腺素为 28.6 nM，IC 50 相当于 21.7 nM）。有趣的是，(+)-para-hydroxy-milnacipran 对去甲肾上腺素摄取的抑制作用比对血清素摄取的抑制作用更强（IC 50 去甲肾上腺素为 10.3 nM，而血清素摄取的 IC 50 相当于 22 nM）。相比之下，(-)-对羟基米那西普兰是一种比去甲肾上腺素摄取更强的血清素摄取抑制剂（IC 50 为 88.5 nM，去甲肾上腺素的 IC 50 为 40.3 nM）。本发明还涉及上述化合物的盐和原药形式。在某些实施方案中，将本发明的化合物和药学上可接受的赋形剂结合起来，制备成制剂给患者用药。最后，本发明涉及治疗患有各种疾病（如抑郁症、慢性疼痛或纤维肌痛）的哺乳动物的方法，包括向有需要的哺乳动物施用治疗有效量的本发明化合物。
• STEREOISOMERS OF P-HYDROXY-MILNACIPRAN, AND METHODS OF USE THEREOF
  申请人：Collegium Pharmaceutical, Inc.

  公开号：EP1578719A2

  公开（公告）日：2005-09-28
• EP1578719A4
  申请人：——

  公开号：EP1578719A4

  公开（公告）日：2006-07-05
• US7038085B2
  申请人：——

  公开号：US7038085B2

  公开（公告）日：2006-05-02
• [EN] STEREOISOMERS OF p-HYDROXY-MILNACIPRAN, AND METHODS OF USE THEREOF<br/>[FR] STEREOISOMERES DE P-HYDROXY-MILNACIPRAN ET PROCEDES D'UTILISATION DE CES DERNIERS
  申请人：COLLEGIUM PHARMACEUTICAL INC

  公开号：WO2004039320A2

  公开（公告）日：2004-05-13

  The present invention relates generally to the enantiomers ofpara-hydroxy-­ milnacipran or congeners thereof. Biological assays revealed that racemic para-hydroxy-­milnacipran is approximately equipotent in inhibiting serotonin and norepinephrine uptake (IC50 = 28.6 nM for norepinephrine, IC50 = 21.7 nM for serotonin). Interestingly, (+) para-­hydroxy-milnacipran is a more potent inhibitor of norepinephrine uptake than serotonin uptake (IC50 = 10.3 nM for norepinephrine, IC50 = 22 nM for serotonin). In contrast, (-)­ para-hydroxy-milnacipran is a more potent inhibitor of serotonin uptake compared to norepinephrin uptake (IC50 = 88.5 nM for norepinephrine, IC50 = 40.3 nM for serotonin). The invention also relates to salts and prodrug forms of the aforementioned compounds. In certain embodiments, the compounds of the present invention and a pharmaceutically acceptable excipient are combined to prepare a formulation for administration to a patient. Finally, the present invention relates to methods of treating mammals suffering from various afflictions, e.g., depression, chronic pain, or fibromyalgia, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of the present invention.