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盐酸特比萘芬

盐酸特比萘芬用途

Terbinafine hydrochloride (TDT 067 hydrochloride) 是治疗真菌感染的抗真菌药物。它是来自念珠菌属的角鲨烯环氧化酶有效的非竞争性抑制剂, Ki值为30 nM。

盐酸特比萘芬作用

盐酸特比萘芬是一种具有广谱抗真菌活性的丙烯胺类药物。本品能特异地干扰真菌麦角固醇的早期生物合成，高选择性地抑制真菌的角鲨烯环氧化酶，使真菌细胞膜形成过程中角鲨烯环氧化反应受阻，从而达到杀灭或抑制真菌的作用。

盐酸特比萘芬名称

[ CAS 号 ]:
78628-80-5

[ 中文名 ]:
盐酸特比萘芬

[ 英文名 ]:
terbinafine hydrochloride

[中文别名 ]:

[英文别名 ]:

MFCD00145430
Lamisil
Terbinafine HCl
Terbinafine hydrochloride
EINECS 245-385-8

盐酸特比萘芬生物活性

[ 描述 ]:

Terbinafine hydrochloride (TDT 067 hydrochloride) 是治疗真菌感染的抗真菌药物。它是来自念珠菌属的角鲨烯环氧化酶有效的非竞争性抑制剂, Ki值为30 nM。

[ 相关类别 ]:

信号通路 >> 抗感染 >> 真菌

研究领域 >> 感染

[ 靶点 ]

Ki: 30 nM (squalene epoxidase)[1]

[体外研究]

特比萘芬在体外对大多数真菌病原体具有主要的杀真菌作用,包括皮肤真菌,二形和丝状真菌。特比萘芬在角鲨烯环氧化作用下特异性地抑制真菌麦角甾醇的生物合成。处理过的真菌细胞迅速积累中间体角鲨烯并且缺乏麦角甾醇途径的最终产物[1]。

[体内研究]

特比萘芬不仅在局部施用后具有活性,而且在口服给药后对实验性皮肤癣菌非常有效。在真菌感染的豚鼠中,特比萘芬第四次治疗后皮肤温度急剧下降[2]。

[动物实验]

豚鼠：已经机械脱毛的豚鼠的背部（腰部）用含有106cfu的杜氏假丝酵母的0.1mL沙氏葡萄糖2％肉汤感染。接种后48小时开始治疗。将试验化合物（特比萘芬）悬浮于2％的tylose和吐温80中，连续9天每天一次通过胃管给药，或者溶解在聚乙二醇400和乙二醇的混合物中，并在身体的感染部位涂抹。用Hrigalski刮刀每天一次，连续1-7天，体积为0.4 mL [2]。

[参考文献]

[1]. Ryder NS, et al. Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol. 1992 Feb;126 Suppl 39:2-8.

[2]. Mieth H, et al. Preclinical evaluation of terbinafine in vivo. Clin Exp Dermatol. 1989 Mar;14(2):104-8.

[相关活性小分子]

盐酸特比萘芬物理化学性质

[ 密度 ]:
1.007g/cm3

[ 沸点 ]:
417.9ºC at 760 mmHg

[ 熔点 ]:
204-208°C

[ 分子式 ]:
C₂₁H₂₆ClN

[ 分子量 ]:
327.891

[ 闪点 ]:
183.7ºC

[ 精确质量 ]:
327.175385

[ PSA ]:
3.24000

[ LogP ]:
5.67930

[ 外观性状 ]:
结晶粉末

[ 折射率 ]:
1.586

[ 储存条件 ]:
-20°C Freezer

盐酸特比萘芬MSDS

盐酸特比萘芬毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QJ8600100

CHEMICAL NAME :: 1-Naphthalenemethanamine, N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-, (E)-, monohydrochloride

CAS REGISTRY NUMBER :: 78628-80-5

LAST UPDATED :: 199510

DATA ITEMS CITED :: 5

MOLECULAR FORMULA :: C21-H25-N.Cl-H

MOLECULAR WEIGHT :: 327.93

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 210 mg/kg/6W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Taste) - change in function

REFERENCE :: LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 339,1483,1992

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

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia Blood - changes in spleen

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: 24,7922,1990

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia Blood - changes in spleen

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: 24,7922,1990

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia Blood - changes in spleen

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: 24,7888,1990 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3960 mg/kg

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

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects

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: 24,7925,1990

盐酸特比萘芬安全信息

[ 符号 ]:

GHS07, GHS09

[ 信号词 ]:
Warning

[ 危害声明 ]:
H315-H319-H335-H410

[ 警示性声明 ]:
P305 + P351 + P338

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xi: Irritant;N: Dangerous for the environment;

[ 风险声明 (欧洲) ]:
R36/37/38

[ 安全声明 (欧洲) ]:
S26-S36/37/39-S61-S60

[ 危险品运输编码 ]:
UN 3077 9/PG 3

[ RTECS号 ]:
QJ8600100

[ 海关编码 ]:
2921499090

盐酸特比萘芬合成路线

盐酸特比萘芬上下游产品

盐酸特比萘芬上游产品

盐酸特比萘芬下游产品

盐酸特比萘芬制备

1.1,1-二氯-3,3-二甲基丁烷的制备在反应瓶中加入氯代叔丁烷186g(2mol)、无水三氯化铝9g,冷至-30ºC.在
搅拌下通入氯乙烯气体(由1,2-二氯乙烷250g,NaOH150g和无水乙醇200ml在50~90ºC反应制得),约1.5h通完,然后在30min内,缓慢升温至-15ºC.在剧烈搅拌下,加入200mol/L盐酸150ml,分出有机层,用水(100ml×2)洗涤,无水MgSO4干燥,过滤#将滤液在室温下减压除去过量的氯乙烯,得粗品1,1-二氯-3,3-二甲基丁烷311g(定量),可直接用于下步反应,分析样品经蒸馏制得.

2.叔丁基乙炔的制备

在反应瓶中加入KOH115g(2mol)和DMSO200ml,反应瓶上的冷凝管通50ºC的温水,反应瓶用油浴加热至140ºC,在搅拌下滴加上步制备的化合物1,1-二氯-3,3-二甲基丁烷77.5g(0.5mol),2h加完,再在140~170ºC搅拌反应10h.得粗产物32g,经蒸馏得经蒸馏得叔丁基乙炔26g,收率63.41%,

3.6,6-二甲基庚-1-烯-4-炔-3-醇的制备

在干燥的反应瓶中加入干燥的镁屑25.20g(1.04mol)、无水乙醚400ml,于室温搅拌下滴加新蒸馏的溴乙烷127g(1.16mol)的无水乙醚80ml溶液,滴加速度以能保持乙醚回流为准#加完后继续搅拌回流反应2h.在室温下,向反应瓶内形成的EtMgBr乙醚溶液中,搅拌滴加上步制备的化合物叔丁基乙炔82g(1mol)的无水乙醚(120ml)溶液,约3h滴加完,室温继续搅拌,直至白色固体形成,放置过夜.在冰/盐浴冷却下,在形成的炔烃格氏试剂的乙醚悬浊液中,于搅拌下滴加新蒸馏的丙烯醛60g(1.07mol)的无水乙醚100ml溶液,约3.5h加完,滴毕,于室温下搅拌过夜.在冰浴冷却下和搅拌下加入NH4Cl饱和水溶液150ml,搅拌充分后静置分层,分出醚层,水层用乙醚(100ml×3)提取,合并有机层#用饱和NaCl水溶液100ml洗涤,无水Na2SO4干燥,过滤,滤液蒸去乙醚后减压蒸馏,得6,6-二甲基庚-1-烯-4-炔-3-醇85g,收率59.06%.

4.1-溴-6,6-二甲基-2-烯-4-炔的制备
在反应瓶中加入48%氢溴酸(HBr)250ml和PBr350g,于40ºC下剧烈搅拌,直至形成均相混合物,然后在23M下搅拌滴加上步制备的化合物6,6-二甲基庚-1-烯-4-炔-3-醇[71g(0.51mol)]的乙醇(85ml)溶液,2h加完,加毕于室温继续搅拌反应2h将反应混合物倒入400ml冰水中,用正己烷(150ml×3)提取,提取液用水洗至中性,无水Na2SO4干燥,过滤,将滤液中正己烷蒸除,得粗品1-溴-6,6-二甲基-2-烯-4-炔100.6g,收率98.6%,可
直接用于特比萘芬的合成.

5.N-甲基-1-萘甲胺的制备
在反应瓶中加入30%甲胺的乙醇溶液300ml,冰浴冷却下,于搅拌下滴加1-氯甲基萘[51g(0.29mol)]的无水乙醇(120ml)溶液,约2h内滴加完,滴毕,搅拌片刻,于室温下放置过夜,反应液浓缩回收溶剂,将剩余物溶于氯仿150ml中,依次用1mol/LNaOH水溶液300ml洗涤,水洗,无水Na2SO4干燥,过滤,滤液浓缩回收溶剂,剩余物减压蒸馏,收集130~140ºC/0.5kPa馏分,得N-甲基-1-萘甲胺30.6g,收率61.6%.

6.N-[(2E)-6,6-二甲基庚-2-烯-4-炔基]-N-甲基-1-萘甲胺盐酸盐(盐酸特比萘芬)的合成
在反应瓶中加入上步制备的化合物N-甲基-1-萘甲胺89.5g(0.52mol、无水Na2CO3 55.3g(0.52mol)和DMF500ml,于冰浴冷却下,搅拌滴加第4步制备的化合物1-溴-6,6-二甲基-2-烯-4-炔100g(0.50ml),用乙醚(200ml×2)提取,有机层用水洗Na2SO4干燥,过滤,滤液蒸去乙醚,剩余物经300g硅胶过滤[用甲苯/乙酸乙酯(4:1)洗脱],滤液和洗脱液合并,蒸去溶剂后的油状物溶于200ml乙醇,在冷却下慢慢加入浓盐酸(搅拌下),调至pH4左右,减压蒸去乙醇,剩余物在室温真空干燥过夜,再将其溶于异丙醇200ml中,冷却,加入乙醚670ml,冰浴冷却放置过夜.过滤,用异丙醇/乙醚(1:1)洗涤滤饼,抽干,得白色结晶,再经异丙醇/乙醚重结晶得盐酸特比萘芬68.2g,收率41.6%.

盐酸特比萘芬海关

[ 海关编码 ]: 2921499090

[ 中文概述 ]:
2921499090 其他芳香单胺及衍生物及它们的盐. 增值税率:17.0% 退税率:9.0% 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

[ Summary ]:
2921499090 other aromatic monoamines and their derivatives; salts thereof VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:30.0%

盐酸特比萘芬文献

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Production of squalene by lactose-fermenting yeast Kluyveromyces lactis with reduced squalene epoxidase activity.

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