5588-33-0

• 常用中文名：美索哒嗪
• 常用英文名：Mesoridazine
• CAS号：5588-33-0
• 分子式：C₂₁H₂₆N₂OS₂
• 分子量：386.57400
• 相关类别： 医药中间体 杂环化合物 哒嗪类化合物
• 发布时间：2018-06-28 19:35:26
• 更新时间：2024-01-09 07:12:00
• 中噻嗪(TPS-23)是噻嗪的代谢物(HY-B0965A),作为口服活性吩噻嗪类抗精神病药物。中瑞他嗪是人类乙醚-a-go-go相关基因(hERG)通道的有效且快速的开放通道阻断剂,在人类胚胎肾293细胞中以550nM(0 mV)的IC50阻断hERG电流[1]。美索里达嗪可用于精神分裂症以及某些其他精神疾病的研究[1][2]。

名称

• 中文名: 美索哒嗪
• 英文名: mesoridazine
• 中文别名: 甲砜哒嗪; 10-[2-(1-甲基哌啶-2-基)乙基]-2-甲基亚砜吩噻嗪
• 英文别名: Mesoridazina; Thioridazine-2-sulfoxide; Lidanar; 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfinylphenothiazine; Tps23; 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-(methylsulfinyl)-10H-phenothiazine; Mesoridazinum; 10-[2-(1-methyl-2-piperidyl)ethyl]-2-methylsulphinylphenothiazine; Lidanil; Calodal; Serentil; Thioridazine thiomethyl sulfoxide; 10-{2-[(RS)1-methylpiperidin-2-yl]ethyl}-2-methylsulfinyl-10H-phenothiazine

物化性质

• 密度: 1.3g/cm3
• 沸点: 570.5ºC at 760mmHg
• 分子式: C₂₁H₂₆N₂OS₂
• 分子量: 386.57400
• 闪点: 298.9ºC
• 精确质量: 386.14900
• PSA: 68.06000
• LogP: 5.76970
• 折射率: 1.694

生物活性

• 描述: 中噻嗪(TPS-23)是噻嗪的代谢物(HY-B0965A),作为口服活性吩噻嗪类抗精神病药物。中瑞他嗪是人类乙醚-a-go-go相关基因(hERG)通道的有效且快速的开放通道阻断剂,在人类胚胎肾293细胞中以550nM(0 mV)的IC50阻断hERG电流[1]。美索里达嗪可用于精神分裂症以及某些其他精神疾病的研究[1][2]。
• 相关类别:
  研究领域 >> 神经疾病
  信号通路 >> 跨膜转运 >> 钾通道
• 靶点:

  IC50: hERG currents[1]

• 体外研究: 中瑞他嗪以浓度依赖性的方式阻断人乙醚-a-go-go相关基因(HERG)电流(0 mV时IC50=550 nM),在HERG激活和饱和的电压范围内,阻断作用显著增加,导致最大HERG通道激活[1]。中硝嗪(15mM；24h)在裸鼠和猪皮中的总吸收率分别为15.94±4.04%和39.24±5.11%[3]。
• 体内研究: 美索里达嗪(15mM；局部给药；一次或每天一次,连续7天)在阻断皮肤疼痛方面显示出有效的活性和长时间的镇痛[3]。在裸鼠背部局部施用6小时后,中硝嗪(15mM)显示皮内浓度为0.34 0.74 nmol/mg[3]。动物模型：8周龄雌性裸鼠[3]剂量：15mM给药：局部给药,一次(镇痛试验)或每天给药,连续7天(刺激试验)。结果：显示镇痛效果。观察到轻微的经表皮水分损失(TEWL)从7.8 g/m2/h增加到9.9 g/m2/h。
• 参考文献:

  [1]. Zhi Su, et al. Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel. J Mol Cell Cardiol. 2004 Jan;36(1):151-60.

  [2]. I S M Salih, et al. Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses. Clin Pharmacol Ther. 2007 Nov;82(5):548-54.

  [3]. Liu KS, et al. Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. Eur J Pharm Biopharm. 2016 Aug;105:59-68.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : SP1880000 CHEMICAL NAME : Phenothiazine, 10-(2-(1-methyl-2-piperidyl)ethyl)-2-(methylsulfinyl) - CAS REGISTRY NUMBER : 5588-33-0 LAST UPDATED : 199512 DATA ITEMS CITED : 10 MOLECULAR FORMULA : C21-H26-N2-O-S2 MOLECULAR WEIGHT : 386.61 WISWESSER LINE NOTATION : T C666 BN ISJ ESO&1 B2- BT6NTJ A HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 86 mg/kg TOXIC EFFECTS : Cardiac - arrhythmias (including changes in conduction) REFERENCE : JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 2,222,1982 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 42 mg/kg TOXIC EFFECTS : Vascular - regional or general arteriolar or venous dilation Lungs, Thorax, or Respiration - chronic pulmonary edema Blood - hemorrhage REFERENCE : ARGPAQ Archives of General Psychiatry. (AMA, 535 N. Dearborn St., Chicago,IL 60610) V.3- 1960- Volume(issue)/page/year: 34,955,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 644 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 509 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 560 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,29,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 26 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,29,1972 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 800 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 405 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 60480 mg/kg/72W-I TOXIC EFFECTS : Brain and Coverings - recordings from specific areas of CNS Skin and Appendages - dermatitis, other (after systemic exposure) Related to Chronic Data - death REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 19,363,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4738 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 103 (estimated) No. of Female Employees: 52 (estimated)

合成路线

50-52-2 ~92% 5588-33-0

文献：Morrow, Ryan J.; Millership, Jeff S.; Collier, Paul S. Helvetica Chimica Acta, 2005 , vol. 88, # 5 p. 962 - 967

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