(R)-2-Phenyl-cyclopropylamine | 1032767-87-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R)-2-Phenyl-cyclopropylamine
• 英文别名: (1R)-2-phenylcyclopropan-1-amine
• CAS: 1032767-87-5
• 化学式: C₉H₁₁N
• 分子量: 133.193
• InChiKey: AELCINSCMGFISI-YGPZHTELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

肝脏的。半衰期：在肝肾功能正常的患者中为1.5-3.2小时

Hepatic. Half Life: 1.5-3.2 hours in patients with normal renal and hepatic function

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

三环类丙咪唑不可逆且非选择性地抑制单胺氧化酶（MAO）。在神经元中，MAO似乎调节在突触放电时释放的单胺水平。由于抑郁症与单胺水平低有关，抑制MAO有助于缓解抑郁症状，因为这会导致中枢神经系统中这些胺类浓度的增加。

Tranylcypromine irreversibly and nonselectively inhibits monoamine oxidase (MAO). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms, as this results in an increase in the concentrations of these amines within the CNS.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 肝毒性

Tranylcypromine（反苯环丙胺）与大多数单胺氧化酶抑制剂一样，会在部分患者中引起短暂的血清转氨酶升高。这些升高通常是轻微的、无症状的，并且是自限性的，不需要调整剂量。Tranylcypromine还与罕见的急性、临床上明显的肝损伤病例有关。描述的少数病例与其他MAO抑制剂引起的病例相似。临床发作的时间通常是1到4个月，血清酶升高的通常模式是肝细胞性（案例1），尽管也有描述胆汁淤积性损伤的情况。免疫过敏特征（皮疹、发热、嗜酸性粒细胞增多）不常见，自身抗体的形成也不常见。

Tranylcypromine, like most monoamine oxidase inhibitors, can cause transient serum aminotransferase elevations in a proportion of patients. These elevations are usually mild, asymptomatic and self-limited and do not require dose modification. Tranylcypromine has also been associated with rare cases of acute, clinically apparent liver injury. The few cases described have resembled those caused by other MAO inhibitors. The time to clinical onset is typically 1 to 4 months and the usual pattern of serum enzyme elevations is hepatocellular (Case 1), although cholestatic injury has also been described. Immunoallergic features (rash, fever, eosinophilia) are uncommon as is autoantibody formation.

来源:LiverTox

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

极少数病例报告出现高血压危象、血清素综合征、肌阵挛、高热、精神障碍和谵妄，其中一些进展至昏迷。此外，在敏感个体或极高剂量下，低血压可能导致休克。[维基百科]

Rare cases have been reported of hypertensive crisis, serotonin syndrome, myoclonus, hyperpyrexia, psychosis, and delirium, some of which progressed to coma. Additionally, in sensitive individuals or at extreme dosages, hypotension may lead to shock. [Wikipedia]

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：由于关于在母乳喂养期间使用反苯环丙胺的信息很少，可能更倾向于使用其他药物，特别是在哺乳新生儿或早产儿时。 ◉ 对哺乳婴儿的影响：一名患有严重抑郁症的妇女在孕期和产后每天服用100至120毫克的反苯环丙胺，以及匹莫奇特、地西泮和阿普唑仑。她在婴儿出生后大约两周内进行母乳喂养，之后婴儿出现腹胀和喂养不耐受。停止母乳喂养后症状得到缓解。 ◉ 对泌乳和母乳的影响：9名受试者平均每天服用29毫克（每天10至40毫克）的口服反苯环丙胺，平均持续16天。血清催乳素水平增加了3微克/升。这些发现对哺乳母亲的临床意义尚不清楚。对于已经建立泌乳的母亲，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Because little information is available on the use of tranylcypromine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants:A woman with severe depression took tranylcypromine 100 to 120 mg daily, as well as pimozide, diazepam and alprazolam during pregnancy and postpartum. She breastfed her infant until about 2 weeks postpartum when the infant developed abdominal distension and feeding intolerance. The symptoms resolved on discontinuation of breastfeeding. ◉ Effects on Lactation and Breastmilk:Nine subjects were treated with an average dose of 29 mg daily (range 10 to 40 mg daily) of oral tranylcypromine for an average of 16 days. Serum prolactin levels increased by 3 mcg/L.The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

MAO抑制剂口服给药吸收良好。这些药物在5-10天内达到对MAO的最大抑制效果。尽管它们与酶的相互作用特性使生物活性延长，但当给药频率低于每日一次时，其临床疗效似乎会降低。/MAO抑制剂/

THE MAO INHIBITORS ARE ABSORBED READILY WHEN GIVEN BY MOUTH. THESE DRUGS PRODUCE MAXIMAL INHIBITION OF MAO WITHIN 5-10 DAYS. ... ALTHOUGH THEIR BIOLOGICAL ACTIVITY IS PROLONGED BECAUSE OF THE CHARACTERISTICS OF THEIR INTERACTION WITH THE ENZYME, THEIR CLINICAL EFFICACY APPEARS TO BE REDUCED WHEN THE DRUG IS GIVEN LESS FREQUENTLY THAN ONCE DAILY. /MAO INHIBITORS/

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (R)-2-Phenyl-cyclopropylamine 、 以 甲醇 为溶剂， 以9.091%的产率得到
  参考文献：
  名称：

  查耳酮基吡啶鎓盐的骨架重塑以获得异吲哚啉多环及其桥联衍生物

  摘要：

  惰性芳香吡啶环的同时解构开环和骨架重建在合成群落中非常重要。然而，该领域的研究仍处于起步阶段。在这里，开发了一种骨架重塑策略，通过脱芳香开环/闭环序列将基于查尔酮的吡啶鎓盐转化为结构有趣的多环异吲哚啉。这些转变涉及吡啶鎓核心解构的两种不同驱动力。一是前所未有地利用了原位生成的环状β-氨基酮的不稳定性，二是所得N ， N-缩酮的不稳定性。所需的异吲哚啉多环可以与各种磷叶立德发生维蒂希反应，以实现结构多样性和复杂性。值得注意的是，通过添加一当量的碱来调整维蒂希条件，引入了额外的桥环。在控制实验和理论计算的基础上提出了一种合理的机制。

  DOI：

  10.1039/d1sc05741c

文献信息

• [EN] TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS<br/>[FR] TRIAZA-SPIRODÉCANONES UTILISÉES EN TANT QU'INHIBITEURS DE DDR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017005583A1

  公开（公告）日：2017-01-12

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.

  本发明涉及式(I)的化合物或其药用盐，其中L和R1至R5如本文所述，以及它们的制备方法、包含它们的药物组合物，以及它们作为药物的用途。
• Novel compounds
  申请人：——

  公开号：US20040023988A1

  公开（公告）日：2004-02-05

  The invention provides novel 1,2,3-triazolo[4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation.

  这项发明提供了新颖的1,2,3-三唑[4,5-d]嘧啶化合物，它们作为药物的用途，含有它们的组合物以及它们的制备方法。
• [EN] LSD1 INHIBITORS<br/>[FR] INHIBITEURS DE LSD1
  申请人：MIRATI THERAPEUTICS INC

  公开号：WO2017079476A1

  公开（公告）日：2017-05-11

  The present invention relates to compounds that inhibit LSD1 activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.

  本发明涉及抑制LSD1活性的化合物。具体而言，本发明涉及化合物、药物组合物和使用方法，例如使用本发明的化合物和药物组合物治疗癌症的方法。
• [EN] SALTS OF AN LSD1 INHIBITOR<br/>[FR] SELS D'UN INHIBITEUR DE LSD1
  申请人：INCYTE CORP

  公开号：WO2017027678A1

  公开（公告）日：2017-02-16

  The present disclosure relates to tosylate salts 1-[4-(methoxymethyl)-4-([(1R,2S)-2- phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid, methods of preparation thereof, and intermediates in the preparation thereof, which are useful in the treatment of the LSD1-associated or mediated diseases such as cancer.

  本公开涉及对甲氧甲基-4-([(1R,2S)-2-苯基环丙基]氨基}甲基)哌啶-1-基甲基}环丁烷羧酸对甲磺酸盐的制备方法及其制备中的中间体，这些中间体在治疗LSD1相关或介导的疾病如癌症方面具有用途。
• FORMULATIONS OF AN LSD1 INHIBITOR
  申请人：Incyte Corporation

  公开号：US20170304282A1

  公开（公告）日：2017-10-26

  The present application relates to pharmaceutical formulations and dosage forms of a lysine specific demethylase-1 (LSD1) inhibitor, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, including methods of preparation thereof, which are useful in the treatment of LSD1 mediated diseases such as cancer.

  本申请涉及一种赖氨酸特异性去甲基化酶-1（LSD1）抑制剂的药物配方和剂型，或其药用可接受的盐、溶剂化合物或水合物，包括其制备方法，这些方法在治疗LSD1介导的疾病如癌症中是有用的。