84625-61-6

• 常用中文名：伊曲康唑
• 常用英文名：Itraconazole
• CAS号：84625-61-6
• 分子式：C₃₅H₃₈Cl₂N₈O₄
• 分子量：705.633
• 相关类别： 原料药 人工合成抗感染类药 抗真菌类药
• 发布时间：2018-02-08 08:00:00
• 更新时间：2024-01-01 20:40:05
• Itraconazole是抗真菌剂。

名称

• 中文名: 伊曲康唑
• 英文名: itraconazole
• 中文别名: 4-[4-[4-[4-[[cis-2-(2,4-二氯苯基)-2-(1H-1,2,4-三唑-1-基甲基)-1,3-二氧戊环-4-基]甲氧基]苯基]哌嗪-1-基]苯基]-2-[(1RS)-1-甲基丙基]-1,2,4-三唑-3-酮; 依他康唑; 斯皮仁诺; 亚特那唑; 4-[4-[4-[4-[[2-(2,4-二氯苯基)-2-(1H-1,2,4-三唑-1-基甲基)-1,3-二氧戊环-4-基]甲氧基]苯基]-1-哌嗪基]苯基]-2,4-二氢-2-(1-甲基丙基)-3H-1,2,4-三唑-3-酮
• 英文别名: 2-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2,4-dihydro-3H-1,2,4-triazol-3-one; Itrizole; Candistat; 3H-1,2,4-Triazol-3-one, 4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihydro-2-(1-methylpropyl)-; Sporanos; 2-sec-Butyl-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2,4-dihydro-3H-1,2,4-triazol-3-one; 2-sec-Butyl-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-1-piperazinyl]phenyl}-2,4-dihydro-3H-1,2,4-triazol-3-one; 2-(Butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorphenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2,4-dihydro-3H-1,2,4-triazol-3-on; MFCD08064196; Itrac; Cladosal 100; Canditral; (±)-1-sec-Butyl-4-[p-[4-[p-[[(2R*,4S*)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-d2-1,2,4-triazolin-5-one; 4-(4-{4-[4-({[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl}oxy)phenyl]piperazin-1-yl}phenyl)-2-(1-methylpropyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; 4-{4-[4-(4-{[(2R,4S)-2-(2,4-Dichlorphenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2-(1-methylpropyl)-2,4-dihydro-3H-1,2,4-triazol-3-on; 4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2-(1-methylpropyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; Itraconazole

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 850.0±75.0 °C at 760 mmHg
• 熔点: 166°C
• 分子式: C₃₅H₃₈Cl₂N₈O₄
• 分子量: 705.633
• 闪点: 467.9±37.1 °C
• 精确质量: 704.239319
• PSA: 104.70000
• LogP: 4.35
• 外观性状: 灰白色结晶固体
• 蒸汽压: 0.0±3.2 mmHg at 25°C
• 折射率: 1.678
• 储存条件: 2-8°C
• 稳定性: Stable. Incompatible with strong oxidizing agents.
• 水溶解性: chloroform: 50 mg/mL, clear, colorless
• 分子结构:

  1、 摩尔折射率：189.33

  2、 摩尔体积（cm³/mol）：502.0

  3、 等张比容（90.2K）：1372.7

  4、 表面张力（dyne/cm）：55.9

  5、 极化率（10-24cm3）：75.05

• 更多:

  1.性状：从甲苯中结晶

  2.熔点（ºC）：166.2

  3.溶解性：几乎不溶于水和稀酸溶液。

生物活性

• 描述: Itraconazole是抗真菌剂。
• 相关类别:
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 抗感染 >> 真菌
  研究领域 >> 感染
• 参考文献:

  [1]. Kim, J., et al., Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell, 2010. 17(4): p. 388-99.

  [2]. Chong, C.R., et al., Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chem Biol, 2007. 2(4): p. 263-70.

  [3]. Shi, W., et al., Itraconazole side chain analogues: structure-activity relationship studies for inhibition of endothelial cell proliferation, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, and hedgehog signaling. J Med Chem, 2011. 54(20): p. 7363-74.

  [4]. Olkkola, K.T., J.T. Backman, and P.J. Neuvonen, Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clinical Pharmacology & Therapeutics, 1994. 55(5): p. 481-485.

MSDS

Itraconazole Revision number: 5 SAFETY DATA SHEET Section1. IDENTIFICATION Product name:Itraconazole Revision number:5 Section2. HAZARDS IDENTIFICATION GHS classification PHYSICAL HAZARDSNot classified HEALTH HAZARDS Acute toxicity (Oral)Category 4 Category 2 Skin corrosion/irritation Serious eye damage/eye irritationCategory 2A Not classified ENVIRONMENTAL HAZARDS GHS label elements, including precautionary statements Pictograms or hazard symbols Signal wordWarning Hazard statementsHarmful if swallowed Causes skin irritation Causes serious eye irritation Precautionary statements: Do not eat, drink or smoke when using this product. [Prevention] Wash hands thoroughly after handling. Wear protective gloves/eye protection/face protection. [Response]IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. Rinse mouth. IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. If eye irritation persists: Get medical advice/attention. IF ON SKIN: Gently wash with plenty of soap and water. If skin irritation occurs: Get medical advice/attention. Take off contaminated clothing and wash before reuse. [Disposal]Dispose of contents/container through a waste management company authorized by the local government. Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substance/mixture:Substance Components:Itraconazole >98.0%(LC)(T) Percent: CAS Number:84625-61-6 Itraconazole Section3. COMPOSITION/INFORMATION ON INGREDIENTS Chemical Formula:C35H38Cl2N8O4 Section4. FIRST AID MEASURES Inhalation:Remove victim to fresh air and keep at rest in a position comfortable for breathing. Get medical advice/attention if you feel unwell. Skin contact:Remove/Take off immediately all contaminated clothing. Gently wash with plenty of soap and water. If skin irritation or rash occurs: Get medical advice/attention. Eye contact:Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. If eye irritation persists: Get medical advice/attention. Call a POISON CENTER or doctor/physician if you feel unwell. Rinse mouth. Ingestion: Protection of first-aiders:A rescuer should wear personal protective equipment, such as rubber gloves and air- tight goggles. Section5. FIRE-FIGHTING MEASURES Dry chemical, foam, water spray, carbon dioxide. Suitable extinguishing media: Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to from the chemical:generate poisonous fume. Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing method according to the surrounding situation is used. Uninvolved persons should evacuate to a safe place. In case of fire in the surroundings: Remove movable containers if safe to do so. Special protectiveWhen extinguishing fire, be sure to wear personal protective equipment. equipment for firefighters: Section6. ACCIDENTAL RELEASE MEASURES Personal precautions,Use personal protective equipment. Keep people away from and upwind of spill/leak. protective equipment and Entry to non-involved personnel should be controlled around the leakage area by emergency procedures: roping off, etc. Environmental precautions: Prevent product from entering drains. Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it. containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with up: appropriate laws and regulations. Section7. HANDLING AND STORAGE Precautions for safe handling Technical measures:Handling is performed in a well ventilated place. Wear suitable protective equipment. Prevent dispersion of dust. Wash hands and face thoroughly after handling. Use a local exhaust if dust or aerosol will be generated. Advice on safe handling: Avoid contact with skin, eyes and clothing. Conditions for safe storage, including any incompatibilities Storage conditions:Keep container tightly closed. Store in a refrigerator. Store away from incompatible materials such as oxidizing agents. Heat-sensitive Packaging material:Comply with laws. Section8. EXPOSURE CONTROLS / PERSONAL PROTECTION Install a closed system or local exhaust as possible so that workers should not be Engineering controls: exposed directly. Also install safety shower and eye bath. Personal protective equipment Respiratory protection: Dust respirator. Follow local and national regulations. Hand protection:Protective gloves. Eye protection:Safety glasses. A face-shield, if the situation requires. Skin and body protection: Protective clothing. Protective boots, if the situation requires. Itraconazole Section9. PHYSICAL AND CHEMICAL PROPERTIES Physical state (20°C):Solid Crystal- Powder Form: Colour:White - Very pale yellow No data available Odour: pH: No data available Melting point/freezing point:169°C Boiling point/range:No data available No data available Flash point: Flammability or explosive limits: Lower:No data available No data available Upper: Relative density:No data available Solubility(ies): [Water]No data available No data available [Other solvents] Section10. STABILITY AND REACTIVITY Chemical stability:Stable under proper conditions. Possibility of hazardous No special reactivity has been reported. reactions: Incompatible materials: Oxidizing agents Hazardous decomposition Carbon monoxide, Carbon dioxide, Nitrogen oxides (NOx), Hydrogen chloride products: Section11. TOXICOLOGICAL INFORMATION orl-rat LD50:>320 mg/kg Acute Toxicity: ivn-rat LD50:40 mg/kg Skin corrosion/irritation: No data available Serious eyeNo data available damage/irritation: Germ cell mutagenicity: No data available Carcinogenicity: IARC =No data available No data available NTP = Reproductive toxicity:No data available XZ5481000 RTECS Number: Section12. ECOLOGICAL INFORMATION Ecotoxicity: Fish:No data available Crustacea:No data available Algae:No data available Persistence / degradability: No data available BioaccumulativeNo data available potential(BCF): Mobility in soil Log Pow:No data available Soil adsorption (Koc):No data available Henry's LawNo data available constant(PaM3/mol): Itraconazole Section13. DISPOSAL CONSIDERATIONS Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system. Observe all federal, state and local regulations when disposing of the substance. Section14. TRANSPORT INFORMATION Hazards Class:Does not correspond to the classification standard of the United Nations UN-No:Not listed Section15. REGULATORY INFORMATION Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002 and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport, loading and unloading were prescribed. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

毒理学数据: 急性毒性LD50(14天)小鼠，大鼠，狗(mg/kg)：＞320，＞320，＞200口服。 CHEMICAL IDENTIFICATION RTECS NUMBER : XZ5481000 CHEMICAL NAME : 3H-1,2,4-Triazol-3-one, 4-(4-(4-(4-((2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triaz ol-1-ylmethyl)- 1,3-dioxolan-4-yl)methoxy)phenyl)-1-piperazinyl)pheny l)-2,4-dihydro-2-(1-m ethylpropyl)- CAS REGISTRY NUMBER : 84625-61-6 LAST UPDATED : 199612 DATA ITEMS CITED : 14 MOLECULAR FORMULA : C35-H38-Cl2-N8-O4 MOLECULAR WEIGHT : 705.71 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 32 mg/kg/8D-I TOXIC EFFECTS : Skin and Appendages - hair REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 293,822,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 140 mg/kg/5W-I TOXIC EFFECTS : Liver - jaundice, other or unclassified Liver - liver function tests impaired Skin and Appendages - dermatitis, other (after systemic exposure) REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 340,251,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 240 mg/kg/6W-I TOXIC EFFECTS : Liver - jaundice, other or unclassified Liver - liver function tests impaired REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 340,251,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >320 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : RINDDG Reviews of Infectious Diseases. (University of Chicago Press, Journals Division, POB 37005, Chicago, IL. 60637) V.1- 1979- Volume(issue)/page/year: 9(Suppl 1),S43,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 40 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 25,381,1991 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >320 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : RINDDG Reviews of Infectious Diseases. (University of Chicago Press, Journals Division, POB 37005, Chicago, IL. 60637) V.1- 1979- Volume(issue)/page/year: 9(Suppl 1),S43,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 46400 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 25,381,1991 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : RINDDG Reviews of Infectious Diseases. (University of Chicago Press, Journals Division, POB 37005, Chicago, IL. 60637) V.1- 1979- Volume(issue)/page/year: 9(Suppl 1),S43,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : >160 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : RINDDG Reviews of Infectious Diseases. (University of Chicago Press, Journals Division, POB 37005, Chicago, IL. 60637) V.1- 1979- Volume(issue)/page/year: 9(Suppl 1),S43,1987 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 29120 mg/kg/1Y-I TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Metabolism (Intermediary) - lipids including transport Related to Chronic Data - death REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 25,381,1991 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 14560 mg/kg/13W-I TOXIC EFFECTS : Endocrine - changes in adrenal weight Related to Chronic Data - death Related to Chronic Data - changes in ovarian weight REFERENCE : RINDDG Reviews of Infectious Diseases. (University of Chicago Press, Journals Division, POB 37005, Chicago, IL. 60637) V.1- 1979- Volume(issue)/page/year: 9(suppl 1),S43,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 7280 mg/kg/91D-C TOXIC EFFECTS : Liver - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 25,381,1991 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 29120 mg/kg/1Y-I TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - changes in calcium Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 25,381,1991 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1760 mg/kg SEX/DURATION : female 8-18 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - other effects Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 25,381,1991

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302-H315-H319-H335
• 警示性声明: P261-P305 + P351 + P338
• 个人防护装备: dust mask type N95 (US);Eyeshields;Faceshields;Gloves
• 危害码 (欧洲): Xi:Irritant
• 风险声明 (欧洲): R36/37/38
• 安全声明 (欧洲): S22-S26-S36
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3
• RTECS号: XZ5481000
• 海关编码: 2934999090

合成路线

78-76-2 89848-41-9 ~46% 84625-61-6

文献：Heeres; Backx; Van Cutsem Journal of Medicinal Chemistry, 1984 , vol. 27, # 7 p. 894 - 900

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制备

从间二氯苯出发，经和酮康唑完全相似的反应可得到化合物(I)。化合物(Ⅰ)再和1-乙酰基-4-(4-羟基苯基)哌嗪缩合，接着水解脱去乙酰基，和对硝基氯苯缩合，氢化还原，氯甲酸酯酰化，然后和水合肼反应后再环合，烷基化得伊曲康唑。其中间体1-乙酰基-4-(4-羟基苯基)哌嗪可以哌嗪为原料，经下面的反应来制备。

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%