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非那雄胺

非那雄胺用途

Finasteride是口服活性的睾酮5α-还原酶抑制剂,Ki为10 nM。

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非那雄胺名称

[ CAS 号 ]:
98319-26-7

[ 中文名 ]:
非那雄胺

[ 英文名 ]:
Finasteride

[中文别名 ]:

非那甾胺

[英文别名 ]:

Proscar
Finasteride
Prostide
Finasterida
MK-906
Chibro-Proscar
Finastid
Propecia
Finpecia
Propecia (TN)

非那雄胺生物活性

[ 描述 ]:

Finasteride是口服活性的睾酮5α-还原酶抑制剂,Ki为10 nM。

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> 5 alpha还原酶

研究领域 >> 癌症

[参考文献]

[1]. Weisser, H. and M. Krieg, In vitro inhibition of androstenedione 5alpha-reduction by finasteride in epithelium and stroma of human benign prostatic hyperplasia. J Steroid Biochem Mol Biol, 1998. 67(1): p. 49-55.

[相关活性小分子]

度他雄胺 | 爱普列特 | 醋酸非那酯 | CGP-53153

非那雄胺物理化学性质

[ 密度 ]:
1.1±0.1 g/cm3

[ 沸点 ]:
576.6±50.0 °C at 760 mmHg

[ 熔点 ]:
253 °C

[ 分子式 ]:
C₂₃H₃₆N₂O₂

[ 分子量 ]:
372.544

[ 闪点 ]:
177.4±30.3 °C

[ 精确质量 ]:
372.277679

[ PSA ]:
58.20000

[ LogP ]:
3.24

[ 外观性状 ]:
白色至灰白色结晶粉末

[ 蒸汽压 ]:
0.0±1.6 mmHg at 25°C

[ 折射率 ]:
1.524

[ 储存条件 ]:
Store at RT

[ 水溶解性 ]:
insoluble

非那雄胺MSDS

非那雄胺毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CL5245000

CHEMICAL NAME :: 4-Azaandrost-1-ene-17-carboxamide, N-(1,1-dimethylethyl)-3-oxo-, (5-alpha,17-beta)-

CAS REGISTRY NUMBER :: 98319-26-7

LAST UPDATED :: 199712

DATA ITEMS CITED :: 13

MOLECULAR FORMULA :: C23-H36-N2-O2

MOLECULAR WEIGHT :: 372.61

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 :: 418 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - ulceration or bleeding from stomach Lungs, Thorax, or Respiration - respiratory depression

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: 28,4091,1994

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 885 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - ulceration or bleeding from small intestine Gastrointestinal - peritonitis

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: 28,4091,1994

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure)

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: 28,4091,1994

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 486 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

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: 28,4091,1994

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 372 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

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: 28,4091,1994

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/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: 28,4091,1994

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

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: 28,4091,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 16425 mg/kg/1Y-I

TOXIC EFFECTS :: Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

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: 28,4121,1994 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3400 mg/kg

SEX/DURATION :: multigeneration

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 42,91,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 mg/kg

SEX/DURATION :: female 6-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Paternal Effects - other effects on male

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 42,483,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6720 mg/kg

SEX/DURATION :: male 12 week(s) pre-mating

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

REFERENCE :: REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 5,337,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3360 mg/kg

SEX/DURATION :: male 12 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

REFERENCE :: REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 5,337,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 162 mg/kg

SEX/DURATION :: female 20-100 day(s) after conception

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

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 55,119,1997

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非那雄胺安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 警示性声明 ]:
P301 + P312 + P330

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

[ 危害码 (欧洲) ]:
T:Toxic

[ 风险声明 (欧洲) ]:
R22;R60;R61

[ 安全声明 (欧洲) ]:
S36/37/39-S45-S53

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
3

[ RTECS号 ]:
CL5245000

[ 海关编码 ]:
2937290090

非那雄胺合成路线

非那雄胺上下游产品

非那雄胺上游产品

非那雄胺下游产品

非那雄胺制备

以孕烯醇酮为原料.先和吡啶作用,再和甲醇钠反应得3-羟基-5-雄甾烯-17β-羧酸甲酯(Ⅲ).再和异丙醇铝在甲苯和环己酮中,回流.过滤,洗涤,干燥,减压浓缩.加入石油醚,于5℃搅拌,抽滤得氧化产物(Ⅳ),收率74.6%.该氧化产物和95%乙醇及10%氢氧化钾溶液,在氮气保护下回流.减压蒸去乙醇后,用6mol几盐酸调至Ph值约为3.抽滤,滤饼用水洗至中性,干燥得水解产物(V),收率96.4%.水解产物溶于叔丁醇中,搅拌下加入无水碳酸钠的水溶液,回流下滴加高碘酸钠和高锰酸钾的水溶液,加毕回流.冷却,过滤.滤液减压蒸去大部分叔丁醇后,冰浴下用6mol/L盐酸调至Ph值约为2.乙酸乙酯提取,提取液用饱和氯化钠洗,干燥.减压蒸干,乙酸乙酯重结晶得开环产物(Ⅵ),收率66%.在冰浴冷却下,往乙二醇中通入氨气,加入开环产物,缓慢升至180℃反应.冷却,加水,用6mol／I.盐酸调至Ph值约为2.滤集固体,水洗至中性,用二甲基甲酰胺重结晶,得环合产物(Ⅶ),收率62.1%.该环合产物和二氧化铂、醋酸及少量高氯酸,在85℃和常压下氢化.滤去催化剂后,减压浓缩至干.残留物用二甲基甲酰胺重结晶,得氢化产物(Ⅷ),收率92.9%.该氢化产物和三苯基膦、甲苯及2,2’-二吡啶二硫化物(DPDS)混合,室温搅拌.柱层析分离得吡啶硫化物(Ⅸ),收率79.0%.该硫化物和无水四氢呋喃及叔丁胺,室温搅拌过夜,加入二氯甲烷,用2mol/L盐酸和饱和氯化钠洗,干燥,减压浓缩.残留物用乙酸乙酯重结晶,得酰胺产物(X),收率77.1%.该酰胺和苯亚硒酸酐及氯苯一起,回流并缓慢蒸出溶剂和生成的水.柱层析分离,粗品用乙酸乙酯重结晶,得白色的非那雄胺晶体,收率52.3％,熔点253～255℃.

1. 孕(甾)烯醇酮21-吡啶碘的制备

在反应器中加入孕(甾)烯醇酮3.0kg(0.47mol)和吡啶8L,搅拌预热至90ºC,于15~30min内往该混合液分批加入碘2.6kg(10.23mol),在加碘期间因放热反应而致使物料产生回流,加毕,保持温度>100ºC继续搅拌60min. 将混合物慢慢冷至室温,过滤,滤饼用吡啶2L洗3次,用乙醚3L洗两次,风干,得到孕(甾)烯醇酮21-吡啶碘粗品5.1kg,该品为棕黄色粉末,mp228~230ºC.

2. 3β-羟基-5-雄(甾)烯-17β-羧酸甲酯的制备

在反应器中加入甲醇钠574g(10.65mol)和甲醇15L(加料前反应器要充分干燥和用N2流驱赶反应器内空气),搅拌溶解,升温至回流,于15min内分批加入孕(甾)烯醇酮21-吡啶碘5.0kg(9.58mol),加毕,黏稠浆状物逐渐

溶解,将深色溶液再搅拌回流1h.2h内冷至45ºC,酯结晶析出,在强烈搅拌下加水15L,用6mol/L盐酸950ml中和,静置陈化1h后,将固体过滤,滤饼用甲醇/水(体积比为1:1)6L洗4次,直至固体颜色被大部分洗掉,抽干,于空气中风干得3β-羟基-5-雄(甾)烯-17β-羧酸甲酯粗品2.709kg,收率85%[以孕(甾)烯醇酮计],mp173~176ºC.

3. 3-羰基-4-雄(甾)烯-17β-羧酸的制备

在反应器中加入3β-羟基-5-雄(甾)烯-17β-羧酸甲酯2.65kg(7.96mol)、甲苯26L和环己酮6.6L,搅拌加热,直至馏出液收集3L.加入浆状异丙醇铝1.46kg(7.15mol)溶于甲苯6L的液体.将混合物回流1h,收集馏出液6L.冷至65ºC后,往混合物中加入活性炭66.g、Supercel 600g和水660ml,搅拌陈化15min后过滤,滤饼用乙酸乙酯6~8L洗数次,合并滤液洗液浓缩,黏稠浆状剩余物加水(500ml×3),减压共沸蒸除残留溶剂.剩余物加己烷4L,于5ºC下搅拌16h.然后在冰/甲醇浴冷却下搅拌1h.过滤,滤饼用冷己烷(500ml×2)洗,抽干,真空(50ºC)干燥, 得1.975kg,mp128~130ºC.

在反应器中加入1.84kg(5.58mol)和10%KOH甲醇溶液9.5L,搅拌和N2保护下回流6H进行皂化.反应毕,用6mol/L盐酸水溶液和水稀释,析出固体,过滤,滤饼真空干燥,得3-羰基-4-雄(甾)烯-17β-羧酸1.71kg,收率62.2%,mp245~248ºC.

4. N-叔丁基-3-羰基-4-雄甾烯-17β-甲酰胺的制备

在反应瓶中加入3-羰基-4-雄(甾)烯-17β-羧酸5.0g(15.8mmol)、无水甲苯50ml和吡啶1.6ml,冷至0ºC ,搅拌滴加草酰氯1.75ml(20mmol)的无水甲苯1.75ml溶液$10ºC以下滴加叔丁胺8.5ml(18mmol)的无水甲苯8.5ml溶液,加毕,室温搅拌10min.倒入冰水70ml,水层用乙酸乙酯(20ml×2)提取,合并有机相,依次用适量2mol/L盐酸溶液、饱和NaHCO3溶液和饱和NaCl溶液洗,无水Na2SO4干燥,过滤,滤液减压浓缩至干,剩余物用乙酸乙酯重结晶,得类白色晶体N-叔丁基-3-羰基-4-雄甾烯-17β-甲酰胺5.5g,收率93.7%,mp214~217ºC.

5. N-叔丁基-5-羰基-17β-氨甲酰基-A-失碳-3,5-开裂-雄甾-3-酸的制备

在反应瓶中加入N-叔丁基-3-羰基-4-雄甾烯-17β-甲酰胺4.0g(10.77mmol)和叔丁醇60ml,搅拌溶解,搅拌下加入无水Na2CO3 1.68g(10.85mmol)的水8ml溶液.搅拌回流下滴加含高碘酸钠16g(74.8mmol)和高锰酸钾13g(0.82mmol)的水60ml溶液.加毕,再搅拌回流30min.冷至室温,滤除固体.滤液减压蒸除大部分叔丁醇,残留液在冰浴下用6mol/L盐酸溶液调pH2左右,析出白色固体$抽滤后干燥,得白色粉末状固体N-叔丁基-5-羰基-17β-氨甲酰基-A-失碳-3,5-开裂-雄甾-3-酸3.55g,收率84.2%,mp202~204ºC.

6. N-叔丁基-3-羰基-4-氮杂-5-雄甾烯-17β-甲酰胺的制备

在反应瓶中加入N-叔丁基-5-羰基-17β-氨甲酰基-A-失碳-3,5-开裂-雄甾-3-酸3.55g(9.07mmol)和乙二醇18ml,搅拌下用冰浴降温,慢慢通入氨气1.2g(70.46mmol),缓慢升温至180ºC,在该温度下搅拌反应2h.冷至室温,加水50ml,抽滤,滤饼用水洗至中性,干燥,得粗品2.5g,用乙酸乙酯重结晶,得白色粉末状固体N-叔丁基-3-羰基-4-氮杂-5-雄甾烯-17β-甲酰胺2.25g,收率66.6%,mp>250ºC.

7. N-叔丁基-3-羰基-4-氮杂-5a-雄甾-17β-甲酰胺的制备

在反应瓶中加入N-叔丁基-3-羰基-4-氮杂-5-雄甾烯-17β-甲酰胺2.5g(6.71mmol),精确称取氧化铂0.25g和冰乙酸15ml,搅拌(快速),用N2置换加氢反应瓶中空气3次,慢慢升温至100ºC,通氢气(常压下),一直通至不吸收氢气为止,一般反应时间为6~8h.降温至室温,真空抽滤,滤饼用少量冰乙酸洗涤,滤饼为废催化剂可回收再生利用.滤液和洗液在减压下蒸除冰乙酸,残余物加适量乙酸乙酯和适量脱色用活性炭,搅拌回流20~30min,过滤,滤液冷却,静置(5ºC左右),析出白色晶体,过滤,抽干,于40~50ºC下真空干燥,得N-叔丁基-3-羰基-4-氮杂-5a-雄甾-17β-甲酰胺的白色结晶固体2.26g,收率90%,mp276~277ºC.

8. 非那雄胺的合成

在反应瓶中加入N-叔丁基-3-羰基-4-氮杂-5a-雄甾-17β-甲酰胺0.5g(1.33mmol)、苯亚硒酸酐0.68g(1.88mmol)和氯苯15ml,加热至回流并慢慢蒸出溶剂和生成水,搅拌反应4h.硅胶柱色谱分离得粗产品0.33g,用乙酸乙酯重结晶,得白色晶体0.26g,收率52.3%,mp276~277ºC.

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非那雄胺海关

[ 海关编码 ]: 2937290090

非那雄胺文献

Anti-proliferative effects of qianliening capsules on prostatic hyperplasia in vitro and in vivo.

Mol. Med. Report. 12 , 1699-708, (2015)

Previous studies by our group showed that Qianliening capsules (QC), a clinically proven effective traditional Chinese formulation that has long been used in the treatment of benign prostatic hyperpla...

Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).

J. Sci. Ind. Res. 65(10) , 808, (2006)

Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI typ...

Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum.

Nat. Chem. Biol. 5 , 765-71, (2009)

Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened...

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非那雄胺

非那雄胺用途

非那雄胺名称

非那雄胺生物活性

非那雄胺物理化学性质

非那雄胺MSDS

详细MSDS(安全技术说明书)

非那雄胺毒性和生态

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

非那雄胺安全信息

非那雄胺合成路线

详细合成路线

非那雄胺上下游产品

非那雄胺上游产品

非那雄胺下游产品

非那雄胺制备

非那雄胺海关

非那雄胺文献

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