16846-24-5

• 常用中文名：交沙霉素
• 常用英文名：Josamycin
• CAS号：16846-24-5
• 分子式：C₄₂H₆₉NO₁₅
• 分子量：827.995
• 相关类别： 原料药 抗生素类药物 大环内酯类药
• 发布时间：2018-02-12 08:00:00
• 更新时间：2024-01-02 14:42:19
• Josamycin (EN-141) 是一种大环内酯类抗生素,对多种病原体, 比如细菌 (bacteria) 具有抗菌活性。 Josamycin (EN-141) 对核糖体的解离常数 Kd 为 5.5 nM。

名称

• 中文名: 交沙霉素
• 英文名: josamycin
• 中文别名: 角沙霉素
• 英文别名: (2S,3R,4R,6S)-6-{[(2R,3S,4R,5R,6S)-6-{[(4R,6S,7R,9R,10R,11E,13E,16R)-4-Acetoxy-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)oxacyclohexadeca-11,13-dien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate; Iosalide; 4-(acetyloxy)-6-((3,6-dideoxy-4-O-(2,6-dideoxy-3-C-methyl-4-O-(3-methyl-1-oxobutyl)-α-L-ribo-hexopyranosyl)-3-(dimethylamino)-β-D-glucopyranosyl)oxy)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxooxacyclohexadeca-11,13-diene-7-acetaldehyde; Vilprafen; Leucomycin V 3-Acetate 4B-(3-Methylbutanoate); MFCD00211043; Leucomycin A3; EN 141; Josamina; EINECS 240-871-6; JOSAMYCIN; carbomycin B; Jomybel; (2S,3R,4R,6S)-6-{[(2R,3S,4R,5R,6S)-6-{[(4R,6S,7R,9R,10R,11E,13E,16R)-4-(acetyloxy)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)oxacyclohexadeca-11,13-dien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate (non-preferred name); YL-704A3; Wilprafen; Josacine; (2S,3R,4R,6S)-6-{[(2R,3S,4R,5R,6S)-6-{[(4R,6S,7R,9R,10R,11E,13E,16R)-4-Acetoxy-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)oxacyclohexadeca-11,13-dien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate (non-preferred name)

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 877.8±65.0 °C at 760 mmHg
• 熔点: 131.5℃
• 分子式: C₄₂H₆₉NO₁₅
• 分子量: 827.995
• 闪点: 484.7±34.3 °C
• 精确质量: 827.466736
• PSA: 206.05000
• LogP: 3.88
• 蒸汽压: 0.0±0.6 mmHg at 25°C
• 折射率: 1.535
• 分子结构:

  1、 摩尔折射率：212.98

  2、 摩尔体积（m³/mol）：684.5

  3、 等张比容（90.2K）：1827.6

  4、 表面张力（3.0 dyne/cm）：50.8

  5、 极化率（0.5 10 ^-24cm ³）：84.43

• 计算化学:

  1、疏水参数计算参考值（XlogP）:2.9

  2、氢键供体数量：3

  3、氢键受体数量：16

  4、可旋转化学键数量:14

  5、互变异构体数量：2

  6、拓扑分子极性表面积（T6PSA）:206

  7、重原子数量：58

  8、表面电荷：0

  9、复杂度:1390

  10、同位素原子数量：0

  11、确定原子立构中心数量：16

  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：2

  14、不确定化学键立构中心数量：0

  15、共价键单元数量：1

• 更多:

  1.性状：未确定

  2.密度（g/mL,25/4℃）：1.133g/mLat 25°C(lit.); 3.相对蒸汽密度（g/mL,空气=1）：未确定

  4.熔点（ºC）：未确定

  5.沸点（ºC,常压）：151-152°C762mm Hg(lit.);

  6.沸点（ºC,5.2kPa）：未确定

  7.折射率：n 20/D 1.528(lit.); 8.闪点（ºC）：110°F; 9.比旋光度（º）：未确定

  10.自燃点或引燃温度（ºC）：未确定

  11.蒸气压（kPa,25ºC）：未确定

  12.饱和蒸气压（kPa,60ºC）：未确定

  13.燃烧热（KJ/mol）：未确定

  14.临界温度（ºC）：未确定

  15.临界压力（KPa）：未确定

  16.油水（辛醇/水）分配系数的对数值：未确定

  17.爆炸上限（%,V/V）：未确定

  18.爆炸下限（%,V/V）：未确定

  19.溶解性：未确定

生物活性

• 描述: Josamycin (EN-141) 是一种大环内酯类抗生素,对多种病原体, 比如细菌 (bacteria) 具有抗菌活性。 Josamycin (EN-141) 对核糖体的解离常数 Kd 为 5.5 nM。
• 相关类别:
  信号通路 >> 抗感染 >> 细菌
  研究领域 >> 感染
• 靶点:

  Kd: 5.5 nM (ribosome)[1]

• 体外研究: 研究表明,对于交沙霉素,核糖体的平均寿命为3小时,并且Josamycin与核糖体结合的解离常数为5.5nM。交沙霉素以氨基酸依赖性方式减慢新生肽的第一个肽键的形成,并完全抑制第二个或第三个肽键的形成,这取决于饱和药物浓度下的肽序列,全长蛋白质的合成完全关闭由Josamycin提供。在饱和药物浓度下,全长蛋白质的合成被Josamycin完全关闭[1]。
• 体内研究: 口服给药后交沙霉素的血液和组织水平为兔子200mg/kg。组织水平通常远高于血液水平,并且在给药后3小时,当血液水平非常低时,组织水平相当高于给药后1小时的组织水平。服药一小时后,肺部水平是所有组织水平中最高的[2]。
• 激酶实验: 在多晶缓冲液中制备交沙霉素，其含有5mM乙酸镁，5mM氯化铵，95mM氯化钾，0.5mM氯化钙，8mM腐胺，1mM亚精胺，5mM磷酸钾和1mM二硫赤藓糖醇。将不同浓度（2,3,4和6μM）的交沙霉素加入到初始化的核糖体中以开始培养。在每个培养时间将1体积的延伸混合物加入1体积的反应混合物中，并在10秒后淬灭反应。结合率由三肽形成核糖体的比例估算[1]。
• 动物实验: 大鼠：将氚标记的交沙霉素（200mg / kg）口服给予大鼠。通过生物测定在1小时和3小时测定血液和组织水平[2]。小鼠：将氚标记的交沙霉素（200mg / kg）口服给予小鼠。通过生物测定在1小时和3小时测定血液和组织水平[2]。
• 参考文献:

  [1]. Lovmar M, et al. Kinetics of macrolide action: the Josamycin and erythromycin cases. J Biol Chem. 2004 Dec 17;279(51):53506-15.

  [2]. Osono T, et al. Pharmacokinetics of macrolides, lincosamides and streptogramins. J Antimicrob Chemother. 1985 Jul;16 Suppl A:151-66.

毒性和生态

毒理学数据: 急性毒性：小鼠口经LD50：>7gm/kg；大鼠LD50：6400mg/kg CHEMICAL IDENTIFICATION RTECS NUMBER : OH4725810 CHEMICAL NAME : Leucomycin V, 3-acetate 4(sup B)-(3-methylbutanoate) CAS REGISTRY NUMBER : 16846-24-5 LAST UPDATED : 199603 DATA ITEMS CITED : 13 MOLECULAR FORMULA : C42-H69-N-O15 MOLECULAR WEIGHT : 828.12 WISWESSER LINE NOTATION : T-16-OV KU MUTJ DOV1 EO1 G1VH I1 JQ P1 FO- BT6OTJ CQ DN1&1 F1 EO- FT6OTJ B1 COV1Y1&1 DQ D1 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 : >7 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,364,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,364,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,364,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 390 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIPDAD Nihon Daigaku No-juigakubu Gakujutsu Kenkyu Hokoku. Research Reports of the College of Agriculture and Veterinary Medicine, Nihon University. (Nihon Daigaku Nojuigakkai, 34-1 Shimouma, 3-chome, Setagaya-ku, Tokyo 154, Japan) No.1- 1953- Volume(issue)/page/year: (35),41,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 6400 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 37,1565,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 780 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 85GDA2 "CRC Handbook of Antibiotic Compounds," Vols.1- , Berdy, J., Boca Raton, FL, CRC Press, 1980- Volume(issue)/page/year: 2,85,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,364,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 385 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIPDAD Nihon Daigaku No-juigakubu Gakujutsu Kenkyu Hokoku. Research Reports of the College of Agriculture and Veterinary Medicine, Nihon University. (Nihon Daigaku Nojuigakkai, 34-1 Shimouma, 3-chome, Setagaya-ku, Tokyo 154, Japan) No.1- 1953- Volume(issue)/page/year: (35),41,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Mammal - species unspecified DOSE/DURATION : 520 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HINAAU Hindustan Antibiotics Bulletin. (Hindustan Antibiotics, Ltd., Pimpri, Poona, India) V.1- 1958- Volume(issue)/page/year: 11,26,1969 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Mammal - species unspecified DOSE/DURATION : 786 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HINAAU Hindustan Antibiotics Bulletin. (Hindustan Antibiotics, Ltd., Pimpri, Poona, India) V.1- 1958- Volume(issue)/page/year: 11,26,1969 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - species unspecified DOSE/DURATION : 385 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HINAAU Hindustan Antibiotics Bulletin. (Hindustan Antibiotics, Ltd., Pimpri, Poona, India) V.1- 1958- Volume(issue)/page/year: 11,26,1969 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9 gm/kg/5W-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 - transaminases REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 22,219,1969 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 21 gm/kg SEX/DURATION : female 7-13 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : JJANAX Japanese Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo 141, Japan) V.21- 1968- Volume(issue)/page/year: 22,219,1969

安全

• 个人防护装备: Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 2
• RTECS号: OH4725810