伊曲康唑

伊曲康唑用途

伊曲康唑是一种三唑类抗真菌药.IC50价值：N /靶点：抗真菌药物：伊曲康唑在药理学上不同于其他唑类抗真菌药物，因为它是该类中唯一一种抑制hedgehog信号通路和血管生成的抑制剂。这些不同的活性与抑制细胞色素P450羊毛甾醇14α-脱甲基酶无关，并且确切的分子靶标仍然未被鉴定。功能上，伊曲康唑的抗血管生成活性已被证明与抑制糖基化，VEGFR2磷酸化和胆固醇生物合成途径有关。证据表明，伊曲康唑抑制hedgehog信号传导的结构决定因素与抗血管生成活性相关。体内：9名志愿者每天口服200mg伊曲康唑或配对安慰剂，持续4天。在第4天，与安慰剂相相比，伊曲康唑使咪达唑仑浓度 - 时间曲线下的面积从10倍增加到15倍（p <0.001），平均峰值浓度增加3到4倍（p <0.001）。在精神运动试验中，相互作用在药物给药后至少6小时具有统计学意义（p <0.05）。伊曲康唑对细胞色素P450IIIA的抑制作用可以解释观察到的药代动力学相互作用[4]。

伊曲康唑名称

[ CAS 号 ]:
84625-61-6

[ 中文名 ]:
伊曲康唑

[ 英文名 ]:
Itraconazole

[中文别名 ]:

[英文别名 ]:

Itrizole
Candistat
Sporanos
MFCD08064196
Itrac
Cladosal 100
Canditral
Itraconazole

伊曲康唑生物活性

[ 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.

[相关活性小分子]

伊曲康唑物理化学性质

[ 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

伊曲康唑MSDS

详细MSDS(安全技术说明书)

伊曲康唑毒性和生态

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

伊曲康唑安全信息

[ 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

伊曲康唑合成路线

详细合成路线

伊曲康唑上下游产品

伊曲康唑上游产品

伊曲康唑下游产品

伊曲康唑制备

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。

伊曲康唑海关

[ 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%

伊曲康唑文献

Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking.

Autophagy 10(7) , 1241-55, (2014)

Glioblastoma is one of the most aggressive human cancers with poor prognosis, and therefore a critical need exists for novel therapeutic strategies for management of glioblastoma patients. Itraconazol...

Antifungal susceptibility and virulence attributes of animal-derived isolates of Candida parapsilosis complex.

J. Med. Microbiol. 63(Pt 11) , 1568-72, (2014)

This study aimed to identify strains of the Candida parapsilosis complex isolated from animals, as well as to assess their in vitro antifungal susceptibility profile and in vitro production of virulen...

European Confederation of Medical Mycology (ECMM) epidemiological survey on invasive infections due to Fusarium species in Europe.

Eur. J. Clin. Microbiol. Infect. Dis. 33(9) , 1623-30, (2014)

In order to better understand the epidemiology of fusariosis in Europe, a survey collecting information on the clinical characteristics of the patients infected by Fusarium as well as on the infecting...

更多文献