(1S,2R)-2-苯基环丙胺 | 3721-28-6

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: (1S,2R)-2-苯基环丙胺
• 英文名称: (1S,2R)-tranylcypromine
• 英文别名: (+)-Tranylcypromine；(1S,2R)-2-phenylcyclopropanamine；(1S,2R)-trans-2-phenylcyclopropylamine；(1S,2R)-2-phenylcyclopropan-1-amine；(+)-(1S,2R)-2-phenylcyclopropylamine；trans-1-Amino-2-phenylcyclopropan；trans-2-phenylcyclopropylamine
• CAS: 3721-28-6
• 化学式: C₉H₁₁N
• 分子量: 133.193
• InChiKey: AELCINSCMGFISI-BDAKNGLRSA-N

物化性质

• 沸点：
  235.73°C (rough estimate)
• 密度：
  1.0050 (rough estimate)
• 颜色/状态：
  Liquid
• 稳定性/保质期：
  STABLE IN LIGHT, HEAT & IN AIR /SULFATE/

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

毒理性

• 肝毒性

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. Tranylcypromine与其他大多数单胺氧化酶抑制剂一样，可能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。临床发病时间通常为1到4个月，血清酶升高的通常模式是肝细胞性的（案例1），尽管也描述了胆汁淤积性损伤。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

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：由于关于在哺乳期间使用反苯环丙胺的信息很少，可能更倾向于选择其他药物，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，以及匹莫齐特、地西泮和阿普唑仑。她在产后大约2周内哺乳她的婴儿，当时婴儿出现了腹胀和喂养不耐受。停止哺乳后症状得到缓解。 ◉ 对泌乳和母乳的影响：9名受试者平均每天接受29毫克（每天10至40毫克）的反苯环丙胺治疗，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)

毒理性

• 相互作用

戊巴比妥睡眠时间被帕纳特延长，表明它能够增强其他药物的作用，可能是通过干扰它们的解毒过程。/帕纳特/

HEXOBARBITAL SLEEPING TIME IS PROLONGED BY PARNATE, INDICATING ITS ABILITY TO POTENTIATE OTHER DRUGS PRESUMABLY BY INTERFERING WITH THEIR DETOXIFICATION. /PARNATE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

MAO抑制剂也能增强外源性给予的胺类物质的效果，比如5-HT（5-羟色胺）和去甲肾上腺素，以及前体物质，比如3,4-羟基苯丙氨酸（多巴）和5-羟基色氨酸。/MAO抑制剂/

MAO INHIBITORS ALSO ENHANCE EFFECTS OF EXOGENOUSLY ADMIN AMINES, SUCH AS 5-HT & NOREPINEPHRINE, AS WELL AS PRECURSORS, SUCH AS 3,4-HYDROXYPHENYLALANINE (DOPA) & 5-HYDROXYTRYPTOPHAN. /MAO INHIBITORS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

度冷丁绝不能用于治疗伴有高血压发作的头痛，当正在服用单胺氧化酶抑制剂的患者报告出现严重搏动性头痛或头部压迫感时，应立即评估其血压。/单胺氧化酶抑制剂/

Meperidine should never be used for ... headaches /with the hypertensive episode/, and blood pressure should be evaluated immediately when a patient taking an MAO inhibitor reports a severe throbbing headache or a feeling of pressure in the head. /MAO INHIBITORS/

来源:Hazardous Substances Data Bank (HSDB)

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)

安全信息

• 危险类别码：
  R20/21,R36/37/38,R25
• WGK Germany：
  3
• 海关编码：
  2921499090
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 3249
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (1S,2R)-2-苯基环丙胺 在 氢氧化钾 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 6.0h， 生成 (+)-7-chloro-6-fluoro-1-<(1'S,2'R)-2'-phenylcyclopropyl>-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Chiral DNA gyrase inhibitors. 1. Synthesis and antimicrobial activity of the enantiomers of 6-fluoro-7-(1-piperazinyl)-1-(2-trans-phenylcyclopropyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

  摘要：

  New quinolone antimicrobial agents (racemic, (1'S,2'R)- and (1'R,2'S)-6-fluoro-7-(1-piperazinyl)-1-(2'-trans-phenyl-1'-cyclopropyl)- 1, 4-dihydro-4-oxoquinoline-3-carboxylic acids) were synthesized, and their in vitro antimicrobial potencies and spectra were determined. As compared to their conceptual parents, these agents retained a considerable amount of the antimicrobial potency and spectra of ciprofloxacin and of 6-fluoro-1-phenyl-7-(1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxy lic acid against Gram-positives. Gram-negatives were considerably less sensitive. The (-)-(1'S,2'R) analogue was the more potent of the enantiomers, but the degree of chiral discrimination by most bacteria was only 4-fold. The 4-fold chiral discrimination was observed also using purified DNA gyrase obtained from Micrococcus luteus, whereas the two enantiomers were essentially equiactive against the enzyme derived from Escherichia coli. These results confirm that there is a substantial degree of bulk tolerance available at N-1 of quinolone antimicrobial agents and suggest that electronic factors controlled by substitution at that site are of considerable importance. On the other hand, chiral recognition brought about by attachment of optically active groups to the N-1 position in these derivatives is relatively small.

  DOI：

  10.1021/jm00160a042
• 作为产物：
  描述：

  trans-2-phenylcyclopropanecarbonitrile 在 Rhodococcus sp. AJ₂₇₀ 作用下， 以 phosphate buffer 为溶剂， 反应 1.0h， 生成 (1S,2R)-2-苯基环丙胺
  参考文献：
  名称：

  Enantioselective synthesis of chiral cyclopropane compounds through microbial transformations of trans-2-arylcyclopropanecarbonitriles

  摘要：

  Enantioselective biotransformations of racemic trans-2-arylcyclopropanecarbonitriles catalyzed by Rhodococcus sp. AJ270 cells proceeded efficiently to give good to excellent optical yields of (-)-(1R,2R)-2-arylcyclopropanecarboxamides and (+)-(1S,21S)-2-arylcyclopropanecarboxylic acids, which were converted into optically active cyclopropylmethylamine and cyclopropylamine derivatives upon reduction and the Curtius rearrangement. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)01031-5

文献信息

• CYCLOPROPYLAMINES AS LSD1 INHIBITORS
  申请人：Incyte Corporation

  公开号：US20150225379A1

  公开（公告）日：2015-08-13

  The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

  本发明涉及环丙胺衍生物，这些衍生物是LSD1抑制剂，可用于治疗癌症等疾病。
• Tranylcypromine Substituted <i>cis</i>-Hydroxycyclobutylnaphthamides as Potent and Selective Dopamine D₃ Receptor Antagonists
  作者：Jianyong Chen、Beth Levant、Cheng Jiang、Thomas M. Keck、Amy Hauck Newman、Shaomeng Wang

  DOI：10.1021/jm401798r

  日期：2014.6.12

  We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over

  我们报告了一类基于反苯环丙胺的强效选择性多巴胺 D 3受体拮抗剂。尽管反苯环丙胺对大鼠 D 3受体的亲和力较低( K i = 12.8 μM)，但我们的努力已经产生了 (1 R ,2 S )- 11 (CJ-1882)，其K i值为 2.7 和 2.8 nM，在分别是大鼠和人多巴胺 D 3受体，并显示出比大鼠和人 D 2受体高10000 倍和 223 倍的选择性。β-抑制蛋白功能测定的评估表明 (1 R ,2 S )- 11是一种有效的竞争性人 D 3受体拮抗剂。
• [EN] (HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS<br/>[FR] COMPOSÉS D'(HÉTÉRO)ARYL-CYCLOPROPYLAMINE À TITRE D'INHIBITEURS DE LSD1
  申请人：ORYZON GENOMICS SA

  公开号：WO2013057322A1

  公开（公告）日：2013-04-25

  The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.

  本发明涉及（杂）芳基环丙胺化合物，特别是如本文所述和定义的公式（I）的化合物，以及它们在治疗中的应用，例如，在治疗或预防癌症、神经系统疾病或状况、或病毒感染方面的应用。
• [EN] (HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS<br/>[FR] COMPOSÉS (HÉTÉRO)ARYLE CYCLOPROPYLAMINES EN TANT QU'INHIBITEURS DE LSD1
  申请人：ORYZON GENOMICS SA

  公开号：WO2013057320A1

  公开（公告）日：2013-04-25

  The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula I as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.

  本发明涉及（杂）芳基环丙胺化合物，特别是如本文所述和定义的公式I的化合物，以及它们在治疗中的用途，例如，在治疗或预防癌症、神经疾病或状况、或病毒感染中的用途。
• AMINOPYRIDINE AND CARBOXYPYRIDINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS
  申请人：Allen Jennifer R.

  公开号：US20100160280A1

  公开（公告）日：2010-06-24

  Pyridine and pyrimidine compounds: or a pharmaceutically acceptable salt thereof, wherein m, n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , and Y are as defined in the specification; or a pharmaceutically acceptable salt thereof, wherein ring A, m, n, y, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , and ring A are as defined in the specification; and or a pharmaceutically acceptable salt thereof, wherein m, n, y, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , X 1 , X 2 , and ring A are as defined in the specification; compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

  吡啶和嘧啶化合物： 或者是根据说明书中定义的药用可接受盐，其中m、n、R1、R2、R3、R4、R5、R6、R7、X1、X2、X3、X4、X5、X6、X7、X8和Y都有所定义； 或者是根据说明书中定义的药用可接受盐，其中环A、m、n、y、R2、R3、R4、R5、R6、R7、R8、R9、X1、X2和环A都有所定义； 或者是根据说明书中定义的药用可接受盐，其中m、n、y、R2、R3、R4、R5、R6、R7、R9、X1、X2和环A都有所定义；含有它们的组合物以及制备这类化合物的方法。还提供了通过抑制PDE10治疗可治疗的疾病或病症的方法，例如肥胖、非胰岛素依赖型糖尿病、精神分裂症、双相情感障碍、强迫症等。

表征谱图