1-[(2R,3S)-3-(3,4-二氯苯基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-基]-N-甲氧基甲亚胺 | 171655-91-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 中文名称: 1-[(2R,3S)-3-(3,4-二氯苯基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-基]-N-甲氧基甲亚胺
• 英文名称: Brasofensine
• 英文别名: (E)-1-[(1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-2-yl]-N-methoxymethanimine
• CAS: 171655-91-7
• 化学式: C₁₆H₂₀Cl₂N₂O
• 分子量: 327.2
• InChiKey: NRLIFEGHTNUYFL-QJDHNRDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  24.8
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

Brasofensine在人类、猴子和大鼠口服给药后经历广泛的首过代谢。它主要发生O-和N-去甲基化和异构化。一些去甲基代谢物进一步转化为葡萄糖苷酸。这些初级代谢物和去甲基brasofensine（M1和M2）的葡萄糖苷酸是人类循环中的主要代谢物，在大鼠和猴子血浆中也观察到。

Brasofensine undergoes extensive first-pass metabolism following oral administration in humans, monkeys, and rats. It primarily underwent O- and N-demethylation and isomerization. Some of the desmethyl metabolites were further converted to glucuronides. These primary metabolites and glucuronides of demethyl brasofensine (M1 and M2) were major circulating metabolites in humans, and were also observed in rat and monkey plasma.

来源:DrugBank

吸收、分配和排泄

• 吸收

Brasofensine在大鼠和猴子口服给药后迅速吸收，血浆峰浓度在0.5-1小时出现，但在人体内 Brasofensine的血浆峰浓度需3-8小时出现。

Brasofensine is rapidly absorbed after oral administration in rats and monkeys, with peak plasma concentrations occurring 0.5-1 hr, but 3-8 hr for brasofensine in humans.

来源:DrugBank

反应信息

• 作为产物：
  描述：

  (1R,2R,3S)-N-normethyl-3-(3,4-dichlorophenyl)tropane-2-O-methyl-aldoxime 生成 1-[(2R,3S)-3-(3,4-二氯苯基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-基]-N-甲氧基甲亚胺
  参考文献：
  名称：

  Journal of labelled compounds and radiopharmaceuticals 1997, 39, 959-972

  摘要：

  DOI：

文献信息

• [EN] PERMANENTLY POSITIVELY CHARGED ANTIDEPRESSANTS<br/>[FR] ANTIDÉPRESSEURS CHARGÉS POSITIVEMENT EN PERMANENCE
  申请人：UNIV AARHUS

  公开号：WO2013026455A1

  公开（公告）日：2013-02-28

  The present invention provides compounds comprising a substructure of below formula 3: or a salt or prodrug thereof and the use of such compounds in treatment of e.g. CNS disorders.

  本发明提供了包含如下式3的亚结构的化合物：或其盐或前药，以及这些化合物在治疗例如中枢神经系统疾病中的用途。
• SUBSTITUTED TRIAZOLOPYRIDINES
  申请人：Gant Thomas G.

  公开号：US20090209550A1

  公开（公告）日：2009-08-20

  Disclosed herein are substituted triazolopyridine serotonin reuptake modulators and/or 5-HT receptor modulators of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文披露了Formula I的替代三唑吡啶类血清素再摄取调节剂和/或5-HT受体调节剂，其制备方法，药物组合物以及使用方法。
• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
• [EN] ALLOSTERIC BINDING COMPOUNDS<br/>[FR] COMPOSÉS DE LIAISON ALLOSTÉRIQUES
  申请人：UNIV AARHUS

  公开号：WO2010094289A1

  公开（公告）日：2010-08-26

  The present invention relates to allosteric binding compounds of formula (I), especially for the treatment of CNS disorders, together with pharmaceutical compositions and methods of treatment including these compounds.

  本发明涉及具有公式(I)的变构结合化合物，尤其用于治疗中枢神经系统疾病，以及包含这些化合物的药物组合物和治疗方法。
• [EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DE RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ARENA PHARM INC

  公开号：WO2017023679A1

  公开（公告）日：2017-02-09

  Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.

  在某些实施例中提供了一些符合本文所定义的A式化合物，其调节5-HT2C受体的活性。在某些实施例中还提供了一些方法，例如用于体重管理、诱导饱腹感、减少食物摄入，以及预防和治疗肥胖、抗精神病药物引起的体重增加、2型糖尿病、普拉德-威利综合征、烟草/尼古丁依赖、药物成瘾、酒精成瘾、病理性赌博、奖赏缺乏综合征和性成瘾，强迫症谱系障碍和冲动控制障碍（包括咬指甲和咬甲症），睡眠障碍（包括失眠、睡眠结构碎裂和慢波睡眠紊乱），尿失禁，精神障碍（包括精神分裂症、厌食症和暴食症），阿尔茨海默病，性功能障碍，勃起功能障碍，癫痫，运动障碍（包括帕金森病和抗精神病药物引起的运动障碍），高血压，血脂异常，非酒精性脂肪肝病，肥胖相关肾脏疾病和睡眠呼吸暂停症。