环苯咯丙醇 | 77-37-2

• 物质功能分类: 原料药 - 神经系统用药 - 抗震颤麻痹药
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 环苯咯丙醇
• 中文别名: 丙环定
• 英文名称: procyclidine
• 英文别名: procyclidine hydrochloride；tricyclamol；1-cyclohexyl-1-phenyl-3-pyrrolidin-1-yl-propan-1-ol；(+/-)-1-Cyclohexyl-1-phenyl-3-pyrrolidino-propan-1-ol；1-Cyclohexyl-1-phenyl-3-pyrrolidino-propan-1-ol；1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol
• CAS: 77-37-2
• 化学式: C₁₉H₂₉NO
• 分子量: 287.445
• InChiKey: WYDUSKDSKCASEF-UHFFFAOYSA-N

物化性质

• 熔点：
  85.5-86.5°
• 沸点：
  429.73°C (rough estimate)
• 密度：
  0.9954 (rough estimate)
• 物理描述：
  Solid
• 颜色/状态：
  Crystals from petroleum ether
• 溶解度：
  In water, 8.59 mg/L at 25 °C (est)
• 蒸汽压力：
  1.22X10-7 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of NOx.
• 碰撞截面：
  172.6 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2154;2154;2175;2160;2177;2167.8;2169;2135;2205;2156

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

在腹腔给药普罗环定后，从大鼠尿液中分离出8种代谢物。它们被鉴定为1-(4-氧环己基)-1-苯基-3-(1-吡咯烷基)-1-丙醇，1-(顺-4-羟基环己基)-1-苯基-3-(1-吡咯烷基)-1-丙醇，1-(反-4-羟基环己基)-1-苯基-3-(1-吡咯烷基)-1-丙醇，(1R,3R,4S,7R)-和(1R,3R,4S,7S)-1-(顺-3,顺-4-二羟基环己基)-1-苯基-3-(1-吡咯烷基)-1-丙醇，(1R,3R,4R,7R)-和(1R,3R,4R,7S)-1-(顺-3,反-4-二羟基环己基)-1-苯基-3-(1-吡咯烷基)-1-丙醇，以及一种(1R,3S,4R,7R)-或(1R,3S,4R,7S)-1-(反-3,反-4-二羟基环己基)-1-苯基-3-(1-吡咯烷基)-1-丙醇，通过比较薄层色谱、气相色谱-质谱和13C-NMR光谱进行鉴定。PMID:6745301

After intraperitoneal administration of procyclidine, eight metabolites were isolated from rat urine. They were identified as 1-(4-oxocyclohexyl)-1-phenyl-3-(1-pyrrolidinyl)-1-propanol, 1-(cis-4-hydroxycyclohexyl)-1-phenyl-3-(1-pyrrolidinyl)-1-propanol, 1-(trans-4-hydrocyclohexyl)-1-phenyl-3-(1-pyrrolidinyl)-1-propanol , (1R,3R,4S,7R)- and (1R,3R,4S,7S)-1-(cis-3,cis-4-dihydroxycyclohexyl)-1-phenyl-3-(1-py rrolidinyl)- 1-propanol, (1R,3R,4R,7R)- and (1R,3R,4R,7S)-1-(cis-3,trans-4-dihydroxycyclohexyl)-1-phenyl- 3-(1-pyrrolidinyl)-1-propanol, and one of both (1R,3S,4R,7R)- or (1R,3S,4R,7S)- 1-(trans-3,trans-4-dihydroxycyclohexyl)-1-phenyl-3-(1-pyrrolidinyl )-1-propanol by comparative TLC, GLC-MS and 13C-NMR spectroscopy. PMID:6745301

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

作用机制尚不清楚。认为普罗环定通过阻断中枢胆碱能受体，从而在基底神经节平衡胆碱能和多巴胺能活动。它的许多效果源于其与阿托品的药理相似性。普罗环定对平滑肌产生抗痉挛作用，可能会导致瞳孔扩张和唾液分泌减少。

The mechanism of action is unknown. It is thought that Procyclidine acts by blocking central cholinergic receptors, and thus balancing cholinergic and dopaminergic activity in the basal ganglia. Many of its effects are due to its pharmacologic similarities with atropine. Procyclidine exerts an antispasmodic effect on smooth muscle, and may produce mydriasis and reduction in salivation.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

化合物：普环啶

Compound:procyclidine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注释：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今日，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按发展药物诱导人类肝损伤风险排名的最大参考药物清单。药物发现今日2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

procyclidine（10毫克）口服和静脉给药后的药代动力学和药效学在六名健康志愿者中进行了研究。治疗顺序是随机的，研究是安慰剂对照且在盲态下进行的。口服给药后，平均血浆峰浓度为116纳克/毫升，平均生物利用度为75%。口服和静脉给药后，procyclidine的分布体积、总清除率和血浆消除半衰期的平均值分别为1升/千克、68毫升/分钟和12小时。...

The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. Treatment order was randomized and the study was placebo-controlled and conducted blind. After oral dosing the mean peak plasma concentration was 116 ng/mL and mean bioavailability was 75%. After both oral and intravenous dosing the mean values for the volume of distribution, total body clearance and plasma elimination half-life of procyclidine were in the order of 1 L/kg, 68 mL/min and 12 hr respectively. ...

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  环苯咯丙醇 生成 (S)-Procyclidine
  参考文献：
  名称：

  对于抗毒蕈碱剂环丙啶和碘化三环酚的对映异构体的绝对构型：（R）-1- [3-环己基-3-羟基-3-苯基-丙基] -1-甲基吡咯烷鎓碘化物的X射线结构分析

  摘要：

  的X射线结构分析（- [R）-1- [3-环己基-3-羟基-3-苯基丙基] -1-甲基吡咯烷鎓碘化物[（[R）-tricyclamol碘，（- [R ）-图2a ]揭示的绝对构抗毒蕈碱药物环丙啶（1a）和三环碘化碘（2a）的对映异构体。（- [R ）- 1A和（- [R ）-图2a是约380-分别和。抗毒蕈碱（隔离的豚鼠回肠）的功效是相应的（S）构型对映异构体的90倍。

  DOI：

  10.1002/jlac.198619860204
• 作为产物：
  描述：

  alpha,alpha-二苯基吡咯烷-1-丙醇 在 溶剂黄146 、 铂 作用下， 生成 环苯咯丙醇
  参考文献：
  名称：

  Adamson et al., Journal of the Chemical Society, 1951, p. 52,58

  摘要：

  DOI：

文献信息

• [EN] IMIDAZOPYRIDINE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS IMIDAZOPYRIDINE ET LEURS UTILISATIONS
  申请人：NEOMED INST

  公开号：WO2014117274A1

  公开（公告）日：2014-08-07

  This invention generally relates to substituted imidazopyridine compounds, particularly substituted 4-(imidazo[1,2-a]pyridin-2-yl)benzamide compounds and salts thereof. This invention also relates to pharmaceutical compositions and kits comprising such a compound, uses of such a compound (including, for example, treatment methods and medicament preparations), processes for making such a compound, and intermediates used in such processes.

  这项发明通常涉及取代咪唑吡啶化合物，特别是取代的4-(咪唑[1,2-a]吡啶-2-基)苯甲酰胺化合物及其盐。这项发明还涉及包含这种化合物的药物组合物和试剂盒，以及这种化合物的用途（包括治疗方法和药物制剂等），制备这种化合物的方法，以及用于这些方法的中间体。
• Piperidine derivatives
  申请人：——

  公开号：US20040142956A1

  公开（公告）日：2004-07-22

  Compounds, compositions and methods are provided that are useful in the treatment or prevention of conditions or disorders associated with a neuropeptide receptor. The subject methods are particularly useful in the treatment and/or prevention of endocrine, metabolic, cardiovascular, neurologic, psychiatric, gastrointestinal, genitourinary and other disorders.

  提供了在治疗或预防与神经肽受体相关的疾病或疾病的化合物、组合物和方法。这些方法特别适用于治疗和/或预防内分泌、代谢、心血管、神经、精神、消化、泌尿生殖和其他疾病。
• [EN] QUATERNARY PIPERIDINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS QUATERNAIRES DE PIPÉRIDINE ET LEURS UTILISATIONS
  申请人：ASTRAZENECA AB

  公开号：WO2010071575A1

  公开（公告）日：2010-06-24

  This invention generally relates to quaternary piperidine compounds, particularly substituted 3-phenylpiperidine compounds and salts thereof. This invention also relates to pharmaceutical compositions comprising such a compound, uses of such a compound (including, for example, treatment methods and medicament preparations), and processes for making such a compound.

  这项发明通常涉及四元哌啶化合物，特别是取代的3-苯基哌啶化合物及其盐。这项发明还涉及包括这种化合物的药物组合物、这种化合物的用途（包括治疗方法和药物制剂等），以及制备这种化合物的方法。
• [EN] ORGANIC COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES
  申请人：INTRA CELLULAR THERAPIES INC

  公开号：WO2014145192A1

  公开（公告）日：2014-09-18

  The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D2 receptor signaling systems.

  该发明涉及特定的取代杂环融合的γ-咖啡碱，其前药，以自由的、药学上可接受的盐和/或基本纯净形式描述，以及其药物组合物，以及在治疗涉及5-HT2A受体、5-羟色胺转运体（SERT）和/或涉及多巴胺D2受体信号系统的疾病中的使用方法。
• [EN] FUSED TRICYCLIC DERIVATIVES FOR THE TREATMENT OF PSYCHOTIC DISORDERS<br/>[FR] DERIVES TRICYCLIQUES ACCOLES POUR LE TRAITEMENT DE TROUBLES PSYCHOTIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2006024517A1

  公开（公告）日：2006-03-09

  Compounds of formula (I) wherein R1, R2, X, A, Y, B, Z1, Q, p, r and s are defined in the specification for treating inter alia psychotic disorders, depressive disorders, anxiety disorders and sexual dysfunctions.

  式中R1、R2、X、A、Y、B、Z1、Q、p、r和s在说明书中定义的用于治疗精神疾病、抑郁障碍、焦虑障碍和性功能障碍的(I)式化合物。

表征谱图