61-72-3

61-72-3结构式
61-72-3结构式
  • 常用中文名:氯唑西林
  • 常用英文名:Cloxacillin
  • CAS号:61-72-3
  • 分子式:C19H18ClN3O5S
  • 分子量:435.881
  • 相关类别: 医药中间体 原料药中间体
  • 发布时间:2018-04-24 08:00:00
  • 更新时间:2024-01-09 18:52:37
  • 氯唑西林是一种口服活性抗菌剂和β-内酰胺酶抑制剂,IC50为0.04µM。氯唑西林可以通过抑制MAPK、NF-κB和NLRP3相关蛋白的激活来抑制金黄色葡萄球菌诱导的炎症反应[1][2][3]。

化源商城直购

中文名 氯唑西林
英文名 cloxacillin
中文别名 氯苯西林
英文别名 xo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylicacid
Cloxacillin (base and/or unspecified salts)
(2S,5R,6R)-6-[[[3-(2-Chlorophenyl)-5-methyl-4-isoxazolyl]carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid
[5-Methyl-3-(o-chlorophenyl)-4-isoxazolyl]penicillin
MFCD00150735
[3-(o-chlorophenyl)-5-methyl-4-isoxazolyl]penicillin
methocillins
[2S-(2a,5a,6b)]-6-[[[3-(2-Chlorophenyl)-5-methyl-4-isoxazolyl]carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid
(2S,5R,6R)-6-({[3-(2-Chlorophenyl)-5-methyl-1,2-oxazol-4-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
3-dimethyl-7-oxo-thyl-4-isoxazolecarboxamido)
Orbenin Extra Dry Cow
brl1621
4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[[3-(2-chlorophenyl)-5-methyl-4-isoxazolyl]carbonyl]amino]-3,3-dimethyl-7-oxo-, (2S,5R,6R)-
cloxacillin
Syntarpen
EINECS 200-514-7
MCIPC
6-<5-Methyl-3-(2-chlor-phenyl)-isoxazolyl-(4)-formamino>-penicillansaeure
描述 氯唑西林是一种口服活性抗菌剂和β-内酰胺酶抑制剂,IC50为0.04µM。氯唑西林可以通过抑制MAPK、NF-κB和NLRP3相关蛋白的激活来抑制金黄色葡萄球菌诱导的炎症反应[1][2][3]。
相关类别
靶点

IC50: 0.04 µM (β-lactamase from wild type A.caviae), 0.3 µM (β-lactamase from mutant A.caviae)[3].

体外研究 氯唑西林(0-2048µg/mL;20-24小时)对金黄色葡萄球菌8325-4和DU1090具有良好的抗菌活性,MIC值均为0.125µg/mL[1]。氯唑西林(0.015625μg/mL;6小时)在体外抑制Hlα的溶血活性,这种抑制作用不仅在与TZ和TZ联合使用时更为明显,而且通过抑制MAPK、NF-κB和NLRP3相关蛋白的激活来抑制炎症反应[1]。细胞活力测定[1]细胞系:金黄色葡萄球菌8325-4,金黄色葡萄杆菌DU1090(一种Hlα缺失菌株)浓度:0-2048µg/mL培养时间:20-24小时结果:抑制金黄色葡萄菌8325-2和DU1090,MIC值均为0.125µg/mL。Western Blot分析[1]细胞系:金黄色葡萄球菌8325-4浓度:0.015625μg/mL(与噻唑嗪(TZ,0.25μg/mL)和四环素(TC,0.03125μg/mL)联合使用)。孵育时间:6h结果:抑制Hlα的表达,与TZ和TC联合使用时抑制作用更明显。Western Blot分析[1]细胞系:RAW264.7细胞(暴露于金黄色葡萄球菌8325-4/DU1090或纯Hlα)浓度:0.015625μ。孵育时间:6小时结果:与TC和TZ联合使用时,抑制MAPK、NF-κB和NLRP3相关蛋白的激活,从而抑制炎症反应。
体内研究 氯唑西林(1.6125 mg/kg;皮下注射;72小时间隔12小时)与噻嗪嗪和四环素联合使用时,可在体内保护小鼠免受金黄色葡萄球菌腹膜炎[1]。氯唑西林(7.5 mg/per;i.p.;从第3天起每天两次,持续3天)与抗IL-15抗体结合时,会发生较轻的滑膜炎,并减少骨侵蚀[3]。动物模型:雌性BALB/c小鼠(6周龄;腹膜炎模型)[1]。剂量:1.6125mg/kg(与TC(3.125mg/kg)和TZ(25mg/千克)联合用药):皮下注射;结果:小鼠肺组织中炎性细胞浸润程度降低,肺泡结构趋于正常。显著减少脾脏和肝组织的病理变化,并减少腹腔内金黄色葡萄球菌的CFU计数。动物模型:雌性野生型C57BL/6小鼠(8周龄;全身性金黄色葡萄球菌诱导的关节炎模型)剂量:7.5 mg/per(与25µg/per抗IL-15抗体联合使用)给药:腹腔注射;从第3天(细菌接种后)开始每天两次,第6天停止。结果:与抗IL-15抗体联合使用时,显示出减少严重滑膜炎和骨侵蚀的活性。
参考文献

[1]. Zhou H, et al. The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation. Int J Biol Macromol. 2022 Feb 15;198:1-10.

[2]. Bergmann B, et al. Antibiotics with Interleukin-15 Inhibition Reduce Joint Inflammation and Bone Erosions but Not Cartilage Destruction in Staphylococcus aureus-Induced Arthritis. Infect Immun. 2018 Apr 23;86(5):e00960-17.

[3]. Lupiola-Gómez PA, et al. Group 1 beta-lactamases of Aeromonas caviae and their resistance to beta-lactam antibiotics. Can J Microbiol. 2003 Mar;49(3):207-15.

密度 1.6±0.1 g/cm3
沸点 689.7±55.0 °C at 760 mmHg
分子式 C19H18ClN3O5S
分子量 435.881
闪点 370.9±31.5 °C
精确质量 435.065582
PSA 138.04000
LogP 2.53
外观性状 白色至灰白色自由流动结晶粉末
蒸汽压 0.0±2.3 mmHg at 25°C
折射率 1.685
分子结构

五、分子性质数据:

1、 摩尔折射率:106.15

2、 摩尔体积(m3/mol):279.2

3、 等张比容(90.2K):833.1

4、 表面张力(dyne/cm):79.2

5、 极化率(10 -24cm 3):42.08

计算化学

1.疏水参数计算参考值(XlogP):无

2.氢键供体数量:2

3.氢键受体数量:7

4.可旋转化学键数量:4

5.互变异构体数量:4

6.拓扑分子极性表面积138

7.重原子数量:29

8.表面电荷:0

9.复杂度:722

10.同位素原子数量:0

11.确定原子立构中心数量:3

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:0

14.不确定化学键立构中心数量:0

15.共价键单元数量:1

毒理学数据:

1 、急性毒性:男人经口TDLo:429mg/kg/10D-I;女人经口TDLo:200mg/kg/5D-I;小孩经口TDLo:5600mg/kg/5W-I;小鼠经脑 LD50:8100ug/kg 2、其它多剂量毒性:大鼠静脉TDLo:7mg/kg/4W-I

3、致突变性:姐妹染色单体exchangeTEST系统:人类淋巴细胞:400mg/L

CHEMICAL IDENTIFICATION

RTECS NUMBER :
XH8720000
CHEMICAL NAME :
4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-(3-(o-chlorophenyl)-S-methyl-4- isoxazolecarboxamido)-3,3-dimethyl-7-oxo-
CAS REGISTRY NUMBER :
61-72-3
LAST UPDATED :
199709
DATA ITEMS CITED :
6
MOLECULAR FORMULA :
C19-H18-Cl-N3-O5-S
MOLECULAR WEIGHT :
435.91

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
429 mg/kg/10D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - interstitial nephritis Blood - eosinophilia
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
200 mg/kg/5D-I
TOXIC EFFECTS :
Liver - jaundice, other or unclassified Liver - liver function tests impaired
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - child
DOSE/DURATION :
5600 mg/kg/5W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - interstitial nephritis Nutritional and Gross Metabolic - body temperature increase
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intracerebral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
8100 ug/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
7 gm/kg/4W-I
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - changes in lung weight Liver - changes in liver weight Endocrine - hypoglycemia

MUTATION DATA

TYPE OF TEST :
Sister chromatid exchange
TEST SYSTEM :
Human Lymphocyte
DOSE/DURATION :
400 mg/L
REFERENCE :
BSIBAC Bolletino della Societe Italiana di Biologia Sperimentale. (Casa Editrice Idelson, Via A. de Gasperi, 55, 80133 Naples, Italy) V.2- 1927- Volume(issue)/page/year: 60,2143,1984

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61-72-3结构式

61-72-3

文献:Journal of the Chemical Society, , p. 5838 - 5845

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61-72-3结构式

61-72-3

文献:Journal of the Chemical Society, , p. 5838 - 5845

~%

61-72-3结构式

61-72-3

文献:Journal of the Chemical Society, , p. 5838 - 5845

~%

61-72-3结构式

61-72-3

文献:Journal of the Chemical Society, , p. 5838 - 5845

~%

61-72-3结构式

61-72-3

文献:Journal of the Chemical Society, , p. 5838 - 5845