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依托度酸

依托度酸用途

Etodolac是非甾体抗炎化合物,对COX的IC50为53.5 nM。

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依托度酸名称

[ CAS 号 ]:
41340-25-4

[ 中文名 ]:
依托度酸

[ 英文名 ]:
Etodolac

[中文别名 ]:

乙哚酸

[英文别名 ]:

Etodolac
etodolic acid
etodolacum [INN_la]
Ultrado
Etodolac [USAN:BAN:INN]
Lodine
Hypen
Tedolan
Zedolac
Etopen

依托度酸生物活性

[ 描述 ]:

Etodolac是非甾体抗炎化合物,对COX的IC50为53.5 nM。

[ 相关类别 ]:

研究领域 >> 炎症/免疫

[ 靶点 ]

COX-2:41 nM (IC50, in CHO cells)

COX-1:∼50000 nM (IC50, in CHO cells)

[参考文献]

[1]. Riendeau D, et al. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br J Pharmacol. 1997 May;121(1):105-17.

[2]. Ito S, Tajima K, Nogawa M et al. Etodolac, a cyclooxygenase-2 inhibitor, attenuates paclitaxel-induced peripheral neuropathy in a mouse model of mechanical allodynia. J Pharmacol Exp Ther. 2012 Jul;342(1):53-60.

[3]. Yanaoka K, Oka M, Yoshimura N et al. Preventive effects of etodolac, a selective cyclooxygenase-2 inhibitor, on cancer development in extensive metaplastic gastritis, a Helicobacter pylori-negative precancerous lesion. Int J Cancer. 2010 Mar 15;126(6):1467-73.

[4]. Matsuyama M, Yoshimura R, Hase T et al. Administration of the selective cyclooxygenase (COX)-2 inhibitor etodolac prolongs cardiac allograft survival in a mouse model. Mol Med Report. 2010 Sep-Oct;3(5):771-4.

[相关活性小分子]

依托度酸物理化学性质

[ 密度 ]:
1.2±0.1 g/cm3

[ 沸点 ]:
507.9±45.0 °C at 760 mmHg

[ 熔点 ]:
145-1480C

[ 分子式 ]:
C₁₇H₂₁NO₃

[ 分子量 ]:
287.353

[ 闪点 ]:
261.0±28.7 °C

[ 精确质量 ]:
287.152130

[ PSA ]:
62.32000

[ LogP ]:
3.59

[ 外观性状 ]:
结晶固体

[ 蒸汽压 ]:
0.0±1.4 mmHg at 25°C

[ 折射率 ]:
1.597

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
可溶于：甲醇

依托度酸MSDS

依托度酸毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UQ0360000

CHEMICAL NAME :: Pyrano(3,4-b)indole-1-acetic acid, 1,3,4,9-tetrahydro-1,8-diethyl-

CAS REGISTRY NUMBER :: 41340-25-4

LAST UPDATED :: 199403

DATA ITEMS CITED :: 13

MOLECULAR FORMULA :: C17-H21-N-O3

MOLECULAR WEIGHT :: 287.39

WISWESSER LINE NOTATION :: T B656 EO HM&TTJ F2 F1VQ J2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 94 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,469,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,469,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 113 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,469,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 593 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,469,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 338 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,469,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 502 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,469,1990

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >4 gm/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,469,1990 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 29200 mg/kg/1Y-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - proteinuria Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,599,1990 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 144 mg/kg

SEX/DURATION :: female 11 day(s) pre-mating female 1-7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,647,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 288 mg/kg

SEX/DURATION :: female 11 day(s) pre-mating female 1-7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,647,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 176 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - sex ratio

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,657,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 52 mg/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,673,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 416 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 40,687,1990

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依托度酸安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H319

[ 警示性声明 ]:
Missing Phrase - N15.00950417-P305 + P351 + P338

[ 个人防护装备 ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T:Toxic

[ 风险声明 (欧洲) ]:
R23/24/25;R40

[ 安全声明 (欧洲) ]:
S22-S36-S45-S26

[ 危险品运输编码 ]:
3249

[ WGK德国 ]:
3

[ RTECS号 ]:
UQ0360000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2934999090

依托度酸合成路线

依托度酸上下游产品

依托度酸上游产品

依托度酸下游产品

依托度酸制备

1.邻乙基苯胺和三氯乙醛水合物及羟胺反应，在酰化的同时形成肟，再在硫酸催化下环合，并用氢化铝锂还原生成吲哚衍生物，和草酰氯及乙醇反应在3位引入1，2-二羰基侧链，氢化铝锂还原为羟乙基，和丙酰乙酸乙酯缩合环合，最后水解生成依托度酸。

2. 邻乙基苯胺的制备

在反应瓶中加入铁粉134g(2.39mol)、水120ml和10%NH4Cl水溶液120g,搅拌升温至60 ºC,于30min内搅拌滴加邻硝基乙苯105g(0.7mol),滴毕#继续搅拌回流反应2~3h.反应毕,自然冷却,放置过夜.过滤,分出油层,减压蒸馏,收集112~116 ºC/3.33kPa馏分,得淡黄色液体邻乙基苯胺60~65g,收率70%~80%.

3. 邻乙基苯肼盐酸盐的制备

在反应瓶中加入化合物邻乙基苯胺24.2g(0.2mol)、浓盐酸150ml和水150ml,用冰盐浴将其冷却至-5 ºC, 于40min内滴加亚硝酸钠14.5g(0.21mol)的水(28ml)溶液(在搅拌下滴加),滴毕,于0 ºC搅拌反应1h. 冷至-15 ºC(!用于冰丙酮浴冷却),于30min内滴加二氯化锡112.5g(0.5mol)和浓盐酸100ml混合的溶液,滴毕,继续搅拌1.5h.反应毕,过滤,滤饼置于另一反应瓶,加入乙醚、10%NaOH溶液适量,搅拌数分钟后,过滤,两次滤液合并,分取有机层,水层用乙醚提取数次,合并有机层,用饱和NaOH水溶液洗涤,无水硫酸钠干燥,过滤,向滤液中通入干燥的氯化氢气体至饱和,析出白色固体,过滤,滤饼用乙醚洗涤,干燥#得白色晶体邻乙基苯肼盐酸盐23.1g,收率67%,mp181~183 ºC.

4. 7-乙基色氨醇的制备

在反应瓶中加入2,3-二氢呋喃16.8g(0.28mol),于10min内滴加化合物邻乙基苯肼盐酸盐24.1g(0.14mol)、水7ml和二氧六环110ml的混合液,滴毕,于100 ºC搅拌6h.反应毕,冷却,加入乙醚适量,过滤去不溶物,分取有机层,用无水硫酸镁干燥.过滤,滤液回收溶剂,冷却,得油状物粗品邻乙基苯肼盐酸盐.其油状物经硅胶柱色谱[洗脱剂:苯/乙酸乙酯(3:1)]纯化,得油状物7-乙基色氨醇6.6g,收率25%.

5. 1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸甲酯的制备

在反应瓶中加入化合物7-乙基色氨醇106g(0.56mol)的甲苯(1050ml)溶液、3-氧代戊酸甲酯92g(0.70mol)和甲醇210ml,降温至0 ºC以下,搅拌下滴加浓硫酸180g(1.8mol),加毕,保温反应1h.反应毕,缓慢加至NaHCO3 300g的水溶液2700ml中,搅拌30min.静置分层,水层用甲苯30ml提取,合并有机层,减压浓缩回收溶剂,剩余物中加入甲醇300ml,搅拌回流30min.降至室温静置过夜.过滤,滤饼用甲醇450ml洗涤至无色,抽干,干燥,得白色颗粒状固体1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸甲酯139g,收率82.7%,mp128~131 ºC.

6. 1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸(依托度酸)的合成

在反应瓶中加入KOH12g(0.124mol)、水86ml和异丙醇6ml,搅拌混合,再加入化合物1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸甲酯12g(0.040mol),搅拌加热至回流,搅拌回流反应1h. 降至室温,用30%盐酸酸化至pH2~3,过滤,得类白色粉末状产物1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸(依托度酸)粗品11.2h,收率97.7%,取1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸(依托度酸)粗品10g(0.0348mol)加至5%乙醇400ml中,加入NaOH1.5g(0.0375mol),搅拌溶解,过滤掉不溶物,滤渣用50%乙醇10ml洗涤.滤液和洗液合并,搅拌下用20%盐酸慢慢酸化至pH,30minpH不变后,将析出结晶过滤,滤饼用50%乙醇15ml洗涤,抽干,干燥,得白色结晶状粉末1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸(依托度9.5g, 精制收率95%,mp145~148 ºC.

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依托度酸海关

[ 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%

依托度酸文献

A new analytical method to determine non-steroidal anti-inflammatory drugs in surface water using in situ derivatization combined with ultrasound-assisted emulsification microextraction followed by gas chromatography-mass spectrometry.

Talanta 129 , 552-9, (2014)

Because of the high stability and potential toxic effects of non-steroidal anti-inflammatory drugs (NSAIDs), it is important to closely monitor their concentrations in the environment using a sensitiv...

Risk of peptic ulcer bleeding associated with Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, low-dose aspirin, and antihypertensive drugs: a case-control study.

J. Gastroenterol. Hepatol. 30(2) , 292-8, (2015)

The associations between antithrombotic or antihypertensive drugs and peptic ulcer bleeding (PUB) remain unknown, particularly in Asia, where Helicobacter pylori infection is prevalent. This study aim...

A method for rapid screening of interactions of pharmacologically active compounds with albumin.

Anal. Chim. Acta 855 , 51-9, (2014)

We determine the association constants for ligand-protein complex formation using the flow injection method. We carry out the measurements at high flow rates (F=1 mL min(-1)) of a carrier phase. There...

更多文献

依托度酸

依托度酸用途

依托度酸名称

依托度酸生物活性

依托度酸物理化学性质

依托度酸MSDS

详细MSDS(安全技术说明书)

依托度酸毒性和生态

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

依托度酸安全信息

依托度酸合成路线

详细合成路线

依托度酸上下游产品

依托度酸上游产品

依托度酸下游产品

依托度酸制备

依托度酸海关

依托度酸文献

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