35711-34-3

• 常用中文名：托美丁钠
• 常用英文名：tolmetin sodium
• CAS号：35711-34-3
• 分子式：C₁₅H₁₄NNaO₃
• 分子量：279.26600
• 相关类别： 原料药 解热镇痛药 非甾抗炎药
• 发布时间：2018-05-06 08:00:00
• 更新时间：2024-01-05 11:27:14
• 托美汀钠是一种口服有效的COX抑制剂,其IC50分别为0.35µM和0.82µM人COX-1和COX-2。托美汀钠是一种非甾体抗炎药(NSAID)[1][2]。

名称

• 中文名: 痛灭定钠
• 英文名: tolmetin sodium
• 中文别名: 托美丁钠; 1-甲基-5-(4-甲基苯甲酰基)-1H-吡咯-2-乙酸钠盐
• 英文别名: Tolmetin sodium anhydrous; Tolumetin sodium dihydrate; sodium 5-(4-methylbenzoyl)-1-methylpyrrole-2-acetate; sodium 1-methyl-5-(4-methylbenzoyl)pyrrole-2-acetate; EINECS 252-687-3; Toleclin; TOLECTIN 600; 1-methyl-5-(p-toluoyl)-1H-pyrrol-2-acetic acid sodium salt; Sodium tolmetin; Sodium tolmetin dihydrate; sodium,2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetate; Tolectin DS; sodium [1-methyl-5-(p-toluoyl)-1H-pyrrol-2-yl]acetate; TOLMETIN SODIUM

物化性质

• 密度: 1.18g/cm3
• 沸点: 483.2ºC at 760 mmHg
• 熔点: 155-157ºC (DECOMPOSES)
• 分子式: C₁₅H₁₄NNaO₃
• 分子量: 279.26600
• 闪点: 246ºC
• 精确质量: 279.08700
• PSA: 62.13000
• LogP: 0.85690

生物活性

• 描述: 托美汀钠是一种口服有效的COX抑制剂,其IC50分别为0.35µM和0.82µM人COX-1和COX-2。托美汀钠是一种非甾体抗炎药(NSAID)[1][2]。
• 相关类别:
  研究领域 >> 癌症
  研究领域 >> 炎症/免疫
  信号通路 >> 免疫及炎症 >> COX
• 靶点:

  Human COX-1:0.35 μM (IC50)

  Human COX-2:0.82 μM (IC50)

• 体外研究: 托美汀钠(0.25mM)不能减轻大鼠脑匀浆中的脂质过氧化。托美汀(0.25、0.5、0.75、1mM)具有清除自由基的特性,但在大鼠脑匀浆中不产生超氧阴离子[3]。托美汀钠(0.001-100μM)对HT-29结肠癌细胞系具有剂量依赖性的抗癌活性[4]。托美汀钠(0-100μM)对成骨细胞生长没有影响[5]。
• 体内研究: 托美汀钠(30100mg/kg；灌胃；单剂量或每日两次,持续3天和14天)在单剂量后4小时显示出最大的溃疡形成作用,而在体重为180-200g的雄性Wistar大鼠中,重复给药3天后和14天后,其显著降低。托美汀以100mg/kg引起胃损伤[2]。托美汀钠(5 mg/kg,每天两次,共5天)预处理显著减轻喹啉酸(QA)诱导的神经毒性[3]。
• 参考文献:

  [1]. T D Warner, et al. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7563-8.

  [2]. Etcheverry SB, et al. Three new vanadyl(IV) complexes with non-steroidal anti-inflammatory drugs (Ibuprofen, Naproxen and Tolmetin). Bioactivity on osteoblast-like cells in culture. J Inorg Biochem. 2002 Jan 1;88(1):94-100.

  [3]. DADAŞ, Yakup, et al. Synthesis and anticancer activity of some novel tolmetin thiosemicarbazides. Marmara Pharmaceutical Journal 19(3) • April 2015

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : UX9290000 CHEMICAL NAME : 1H-Pyrrole-2-acetic acid, 1-methyl-5-(p-toluoyl)-, sodium salt CAS REGISTRY NUMBER : 35711-34-3 LAST UPDATED : 199504 DATA ITEMS CITED : 16 MOLECULAR FORMULA : C14-H12-N-O3.Na MOLECULAR WEIGHT : 265.26 WISWESSER LINE NOTATION : T5MJ BVR D1& E1VO &-NA- HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - child DOSE/DURATION : 2520 mg/kg/8W-I TOXIC EFFECTS : Blood - thrombocytopenia REFERENCE : ARHEAW Arthritis and Rheumatism. (Arthritis Foundation, 1314 Spring St., NW, Atlanta, GA 30309) V.1- 1958- Volume(issue)/page/year: 25,1144,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 538 mg/kg/61D-I TOXIC EFFECTS : Skin and Appendages - dermatitis, allergic (after systemic exposure) REFERENCE : JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 243,1263,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 8 mg/kg TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions Vascular - BP lowering not characterized in autonomic section Vascular - shock REFERENCE : JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 240,246,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 8 mg/kg TOXIC EFFECTS : Spinal Cord - meningeal changes Sense Organs and Special Senses (Eye) - conjunctive irritation Liver - liver function tests impaired REFERENCE : JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 245,67,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 914 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 770 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,532,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1050 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,532,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >724 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,532,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 899 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 690 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,532,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 670 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,532,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >622 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,532,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >800 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 1584 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,233,1977 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 100 mg/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 38,238,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5369 No. of Facilities: 53 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 2069 (estimated) No. of Female Employees: 1109 (estimated)

安全

• 海关编码: 2933990090

合成路线

1310-73-2 33369-52-7 ~% 35711-34-3

文献：WO2009/72139 A1, ; Page/Page column 13 ;

海关

海关编码	2933990090
中文概述	2933990090. 其他仅含氮杂原子的杂环化合物. 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, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%