55142-85-3

• 常用中文名：噻氯匹啶
• 常用英文名：Ticlopidine
• CAS号：55142-85-3
• 分子式：C₁₄H₁₄ClNS
• 分子量：263.786
• 相关类别： 原料药 血液系统用药 抗凝血药及抗血小板药
• 发布时间：2018-08-24 09:11:49
• 更新时间：2025-08-21 17:42:33
• 噻氯匹定(PCR 5332)是一种抗血栓前药,作为CD39的变构非竞争性抑制剂,IC50为81.7 µM.噻氯匹定阻断数种NTPDase同功酶,IC50为170 μM和149 对于NTPDase2和NTPDase3,分别为µM[1]。噻氯匹定是CYP2C19人肝细胞色素的抑制剂。噻氯匹定抑制CYP2C9和CYP3A4的IC50分别为26.0和32.3μM[2][3]。

名称

• 中文名: 噻氯匹定
• 英文名: ticlopidine
• 中文别名: 5-(2-氯苄基)4,5,6,7-四氢噻吩并[3,2-C]吡啶; 氯苄噻唑啶
• 英文别名: 5-[(2-Chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine; TICLID; 5-[(2-chlorophenyl)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridine; MFCD00661081; Thieno[3,2-c]pyridine, 5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydro-; 5-(o-Chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine; Ticlopidina; 1,2,3,4-tetrahydro-N-<(2-chlorophenyl)methyl>-thieno<3,2-c>pyridine; Ticlopidine; Ticlopidine [INN:BAN]; Ticlopidinum [INN-Latin]; Ticlopidinum; Thieno(3,2-c)pyridine, 5-((2-chlorophenyl)methyl)-4,5,6,7-tetrahydro-; Ticlopidine (INN); 5-(2-Chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine; UNII-OM90ZUW7M1; [14C]-Ticlopidine; EINECS 259-498-5; Ticlopidina [INN-Spanish]

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 367.3±37.0 °C at 760 mmHg
• 分子式: C₁₄H₁₄ClNS
• 分子量: 263.786
• 闪点: 175.9±26.5 °C
• 精确质量: 263.053558
• PSA: 31.48000
• LogP: 3.77
• 外观性状: 浅黄色固体
• 蒸汽压: 0.0±0.8 mmHg at 25°C
• 折射率: 1.638
• 储存条件: -20℃
• 分子结构:

  1、 摩尔折射率：74.43

  2、 摩尔体积（cm³/mol）：207.0

  3、 等张比容（90.2K）：554.7

  4、 表面张力（dyne/cm）：51.5

  5、 极化率（10-24cm3）：29.51

• 计算化学:

  1.疏水参数计算参考值（XlogP）:3.6

  2.氢键供体数量:0

  3.氢键受体数量:2

  4.可旋转化学键数量:2

  5.互变异构体数量:无

  6.拓扑分子极性表面积31.5

  7.重原子数量:17

  8.表面电荷:0

  9.复杂度:261

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

• 更多:

  1.性状：白色或微黄色结晶性粉末

  2.熔点：190

  3.溶解性：易溶于冰醋酸、乙醇或水，溶于95％乙醇、甲醇或氯仿，微溶于正丁醇，不溶于乙醚。

生物活性

• 描述: 噻氯匹定(PCR 5332)是一种抗血栓前药,作为CD39的变构非竞争性抑制剂,IC50为81.7 µM.噻氯匹定阻断数种NTPDase同功酶,IC50为170 μM和149 对于NTPDase2和NTPDase3,分别为µM[1]。噻氯匹定是CYP2C19人肝细胞色素的抑制剂。噻氯匹定抑制CYP2C9和CYP3A4的IC50分别为26.0和32.3μM[2][3]。
• 相关类别:
  研究领域 >> 心血管疾病
  信号通路 >> 代谢酶/蛋白酶 >> 细胞色素P450
• 靶点:

  Cytochrome P450[1]

• 体外研究: 噻氯匹定具有抗人CD39的活性,表观Ki、app值为14µM[1]。噻氯匹定抑制在Ki值为127±12的COS-7细胞中表达的重组人CD39 µM[1]。生长速度在培养的第一天受到影响,噻氯匹定(30和150µM)会在接下来的几天降低其效果[4]。细胞增殖试验[4]细胞系：人内皮细胞浓度：30和150µM培养时间：2,6；10天的结果：与对照组相比,经处理的细胞生长较慢,这种效应与培养基中噻氯匹定的浓度有关。
• 体内研究: 口服含10mg/kg噻氯匹定的氯沙坦可显著增加AUC(65.0%),表明噻氯匹定可有效抑制氯沙坦在肠道和/或肝脏中的代谢[3]。动物模型：雄性Sprague-Dawley大鼠(7-8周龄,体重270-300g)[3]剂量：4或10mg/kg给药：口服氯沙坦前30min口服。结果：口服氯沙坦和10mg/kg噻氯匹定后,氯沙坦的AUC和Cmax显著高于对照组大鼠(分别为65.0%和49.4%)。
• 参考文献:

  [1]. Laura Schäkel, et al. 2-Substituted thienotetrahydropyridine derivatives: Allosteric ectonucleotidase inhibitors. Arch Pharm (Weinheim). 2021 Dec;354(12):e2100300.

  [2]. I.KRASLOVA1, et al. Ticlopidine-Induced Cholestatic Inflammatory Hepatitis: New Insights into Pathogenetic Mechanisms of Drug-Related Hepatotoxicity.

  [3]. Si-hyung Yang, et al. Effects of ticlopidine on pharmacokinetics of losartan and its main metabolite EXP-3174 in rats. Acta Pharmacol Sin. 2011 Jul;32(7):967-72.

  [4]. F Piovella, et al. The effect of Ticlopidine on human endothelial cells in culture. Thromb Res. 1984 Feb 1;33(3):323-32.

毒性和生态

毒理学数据: 急性毒性LD50小鼠(24h)：55mg/kg静脉注射；＞300mg/kg口服 CHEMICAL IDENTIFICATION RTECS NUMBER : XJ9089200 CHEMICAL NAME : Thieno(3,2-c)pyridine, 4,5,6,7-tetrahydro-5-((2-chlorophenyl)methyl)- CAS REGISTRY NUMBER : 55142-85-3 LAST UPDATED : 199712 DATA ITEMS CITED : 12 MOLECULAR FORMULA : C14-H14-Cl-N-S MOLECULAR WEIGHT : 263.80 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 336 mg/kg/47D-I TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes Blood - agranulocytosis Blood - thrombocytopenia REFERENCE : APHRER Annals of Pharmacotherpy. (Harvey Whitney Books Co., POB 42696, Cincinnati, OH 45242) V. 26- 1992- Volume(issue)/page/year: 28,1236,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 600 mg/kg/60D-I TOXIC EFFECTS : Blood - aplastic anemia Blood - changes in bone marrow (not otherwise specified) Nutritional and Gross Metabolic - body temperature increase REFERENCE : IJMDAI Israel Journal of Medical Sciences. (POB 1435, Jerusalem 91013, Israel) V.1- 1965- Volume(issue)/page/year: 31,444,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 429 mg/kg/6OD-I TOXIC EFFECTS : Gastrointestinal - hypermotility, diarrhea REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,407,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 100 mg/kg/10D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - urine volume decreased Blood - eosinophilia REFERENCE : AJKDDP American Journal of Kidney Diseases. (Grune & Stratton, Inc., Journal Subscription Dept., POB 6280, Duluth, MN 55806) V.1- 1981- Volume(issue)/page/year: 25,934,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1780 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 70 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 600 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1250 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 88 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : >6 gm/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 500 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening Skin and Appendages - hair REFERENCE : NDADD8 New Drugs Annual: Cardiovascular Drugs. (New York, NY) V.1-2, 1983-84. For publisher information, see NCDREP. Volume(issue)/page/year: 1,295,1983

安全

• 危害码 (欧洲): C,Xi
• 风险声明 (欧洲): R34:Causes burns.
• 安全声明 (欧洲): S26-S27-S36/37/39-S45
• 危险品运输编码: UN 3261 8/PG 3
• WGK德国: 3
• 海关编码: 2934999090

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制备

【方法一】
方法1：噻吩溶于无水乙醚，在0℃缓慢滴加丁基锂乙醚溶液，再在室温搅拌。然后在0～5℃滴加环氧乙烷乙醚溶液，再室温反应。用盐酸调至中性．分出醚层，回收乙醚，收集97～101℃/933Pa的馏分，得2-羟乙基噻吩，收率72%。将其溶于吡啶，在5℃以下分批加入对甲苯磺酰氯，室温搅拌。用2.5mol/L硫酸调至Ph值4-5。分出油层，水洗至中性，干燥，收集70-75℃/533Pa的馏分，冰箱放置过夜，得磺酰化产物，收率87%。把磺酰化产物和邻氯苄胺溶于甲苯，回流。滤除固体，滤液用3mol/L盐酸提取。提取液浓缩，放置。滤集沉淀，用丙酮洗，得化合物(Ⅰ)，收率62%。将(Ⅰ)、36%甲醛和水，90℃搅拌。用盐酸调至Ph值3-4，回流。放冷，滤除沉淀，滤液用稀氢氧化钠碱化，异丙醚提取。提取液水洗，干燥，浓缩得油状物。加少许浓盐酸和丙酮，放置，析出结晶，即为盐酸噻氯匹定，收率54%，熔点189-190℃。
方法2：噻吩甲醛和硝基甲烷溶于甲醇，维持在5℃以下，滴加40%氢氧化钠溶液。加毕，搅拌。加入水，缓慢倒人盐酸溶液。滤集沉淀，水洗，烘干，得2-硝基乙烯噻吩，收率。70%。
硼氢化钾溶于四氢呋喃，在0℃缓慢滴加三氟化硼乙醚。在0～5℃搅拌后，滴加2-硝基乙烯噻吩的四氢呋喃溶液，室温搅拌。加入甲苯进行蒸馏，当内温达90℃时，改成回流。冷至0℃，加入水，用1mol/L盐酸缓慢酸化。加热至80℃，搅拌。冷至40～50℃后，分取水层，甲苯层用1mol/L盐酸洗。合并水层，用氢氧化钠溶液调至Ph值13。用二氯甲烷提取，提取液水洗，干燥，浓缩，得2-噻吩乙胺，收率80%。
在搅拌下，往2-噻吩乙胺中滴加36%甲醛水溶液，回流。用二氯甲烷提取，提取液水洗，浓缩，得亚甲胺化合物(Ⅱ)，收率92%。
该亚甲胺化合物和6mol/L盐酸于室温搅拌，加氢氧化钠溶液至Ph值13，用二氯甲烷提取。提取液水洗，干燥，浓缩，得化合物(Ⅲ)，收率100%。
化合物(Ⅲ)-2-氯苄基氯、三乙胺和乙腈，室温搅拌。减压回收乙腈，加入甲苯和水，搅匀。分取甲苯层，水层用甲苯提取。甲苯液合并，水洗，干燥。用氯化氢的异丙醇溶液调至Ph值2，搅拌。放冷后过滤，用无水乙醇重结晶，得白色的盐酸噻氯匹定，收率75%，熔点206～207℃。
方法3：以4，5，6，7-四氢噻吩并[3，2-c]为原料，直接和2，α-二氯甲苯反应，即得噻氯匹定。或者4，5，6，7-四氢噻吩和2-氯苯甲醛反应，也可得到噻氯匹定。

海关

海关编码	2934999090
中文概述	2934999090. 其他杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%