噻氯匹啶

噻氯匹啶用途

【用途一】
血小板膜稳定剂，有抑制血小板聚集，阻止血栓形成，降低血液粘稠度，改善微循环等作用。其作用优于阿司匹林、磺吡唑酮和潘生丁。用于血管手术和体外循环发生的血栓、动脉闭塞性脉管炎及闭塞性动脉硬化。可降低中风、心肌梗塞或血栓栓塞性中风的血管坏死发生率。

噻氯匹啶名称

[ CAS 号 ]:
55142-85-3

[ 中文名 ]:
噻氯匹定

[ 英文名 ]:
Ticlopidine

[中文别名 ]:

氯苄噻唑啶

[英文别名 ]:

TICLID
MFCD00661081
Ticlopidina
Ticlopidine
Ticlopidine [INN:BAN]
Ticlopidinum [INN-Latin]
Ticlopidinum
Ticlopidine (INN)
UNII-OM90ZUW7M1
[14C]-Ticlopidine

噻氯匹啶生物活性

[ 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.

噻氯匹啶物理化学性质

[ 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℃

噻氯匹啶毒性和生态

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

噻氯匹啶安全信息

[ 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

噻氯匹啶合成路线

详细合成路线

噻氯匹啶上下游产品

噻氯匹啶上游产品

噻氯匹啶下游产品

噻氯匹啶制备

【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。

噻氯匹啶海关

[ 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%