制备方法

按照采用的原料划分,该品合格路线主要有两条,一是以对氨基苯酚为原料经重氮化;置换制得对氯苯酚,再经缩合;水解,酸化生成对氯苯氧异丁酸,最后酯化得安妥明。这条路线步骤较长,所用原料对氨基酚不稳定,但比较成熟。二是以苯酚为原料,经缩合生成苯氧异丁酸,再于乙醇中通氯,进行氯化及酯化反应生成安妥明。

合成制备方法

按照采用的原料划分，该品合格路线主要有两条，一是以对氨基苯酚为原料经重氮化；置换制得对氯苯酚，再经缩合；水解，酸化生成对氯苯氧异丁酸，最后酯化得安妥明。这条路线步骤较长，所用原料对氨基酚不稳定，但比较成熟。二是以苯酚为原料，经缩合生成苯氧异丁酸，再于乙醇中通氯，进行氯化及酯化反应生成安妥明。

用途简介

用于脑血栓、脑动脉硬化、脑外伤后遗症、内耳眩晕症、冠状动脉硬化及由末梢循环不良引起的疾病。

用途

降血脂药。能抑制胆固醇和甘油三酯的合成，增加固醇类的排泄，降低血中ULDL的含量，临床证明该品降甘油三酯作用较降胆醇作用明显，作用强时甘油三酯可降低30-40%，胆固醇可降低15-20%，适用于Ⅲ；Ⅳ；Ⅴ型高血酯症，对Ⅲ型尤佳，对部分Ⅱb型也有效，此外，该品能降低血浆纤维蛋白元的含量和血小板的粘性，因而，有利于防止血栓的形成，减少心肌梗塞的发病率，用于高酯血症及动脉硬化症等。服用该品个别病人有恶心；呕吐；食欲不振；腹胀；腹泻等症状。为了减少胃肠道反应，开始时宜采用小剂量，以后逐渐增量，但在治疗的第一个月应达到规定剂量。停药时最好也采用递减方法。肝肾功能不全者慎用。孕妇忌用。毒性：口服LD50小鼠1.28g/kg；大鼠1.65g/kg。

海关代码：

2918990090

WGK_Germany：

3
德国有关水污染物质的分类清单

危险类别码：

R22;R40

安全说明：

S26-S36/37/39-S61-S45-S36/37

RTECS号：

UE9480000

安全标志：

S26:万一接触眼睛，立即使用大量清水冲洗并送医诊治。
S61:避免排放到环境中。参考专门的说明/安全数据表。
:

危险标志：

Xn:Harmful;

CHEMICAL IDENTIFICATION

RTECS NUMBER :

UE9480000

CHEMICAL NAME :

Propionic acid, 2-(p-chlorophenoxy)-2-methyl-, ethyl ester

CAS REGISTRY NUMBER :

637-07-0

BEILSTEIN REFERENCE NO. :

1913459

LAST UPDATED :

199706

DATA ITEMS CITED :

51

MOLECULAR FORMULA :

C12-H15-Cl-O3

MOLECULAR WEIGHT :

242.72

WISWESSER LINE NOTATION :

GR DOX1&1&VO2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

4232 mg/kg/57W-I

TOXIC EFFECTS :

Behavioral - muscle weakness Behavioral - muscle contraction or spasticity Musculoskeletal - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1071 ug/kg

TOXIC EFFECTS :

Behavioral - tremor

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

80 mg/kg/2D-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

171 mg/kg/6D-I

TOXIC EFFECTS :

Behavioral - muscle weakness Musculoskeletal - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

940 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

910 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1220 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

540 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1370 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

1280 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

2400 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

1260 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - species unspecified

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7 gm/kg/14D-I

TOXIC EFFECTS :

Liver - changes in liver weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3750 mg/kg/30D-C

TOXIC EFFECTS :

Liver - other changes Kidney, Ureter, Bladder - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

14 gm/kg/4W-I

TOXIC EFFECTS :

Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

14700 mg/kg/7W-C

TOXIC EFFECTS :

Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - catalases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1698 mg/kg/6D-C

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Metabolism (Intermediary) - lipids including transport

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

7 gm/kg/14D-I

TOXIC EFFECTS :

Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

100 gm/kg/72W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1050 mg/kg

SEX/DURATION :

female 16-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

14 gm/kg

SEX/DURATION :

female 2 week(s) pre-mating - 3 week(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3960 mg/kg

SEX/DURATION :

male 22 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

960 mg/kg

SEX/DURATION :

female 17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

1440 mg/kg

SEX/DURATION :

female 14-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - other effects to embryo

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1300 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

DNA damage

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Sister chromatid exchange

TEST SYSTEM :

Rodent - hamster Ovary

DOSE/DURATION :

100 umol/L/1H

REFERENCE :

CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 5,703,1984 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,39,1980 IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,39,1980 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 IARC Cancer Review:Group 3 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - T0426 No. of Facilities: 28 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 4648 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - T0426 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 323 (estimated) No. of Female Employees: 176 (estimated)

生态数据：

通常对水是不危害的，若无政府许可，勿将材料排入周围环境。

中国海关编码：2918990090

概述：

2918990090. 其他含其他附加含氧基羧酸（包括酸酐、酰卤化物、过氧化物和过氧酸及该税号的衍生物）. 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:30.0%

申报要素：

品名, 成分含量, 用途

摘要/Summary：

2918990090. other carboxylic acids with additional oxygen function and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

分子结构数据

1、   摩尔折射率：62.73

2、   摩尔体积（m³/mol）：211.4

3、   等张比容（90.2K）：518.5

4、   表面张力（dyne/cm）：36.1

5、   极化率（10^-24cm³）：24.86

计算化学数据

1.疏水参数计算参考值（XlogP）:无

2.氢键供体数量:0

3.氢键受体数量:3

4.可旋转化学键数量:5

5.互变异构体数量:无

6.拓扑分子极性表面积35.5

7.重原子数量:16

8.表面电荷:0

9.复杂度:232

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

• 
  氯贝特质谱(MS)
• 
  氯贝特红外图谱(IR1)