10118-90-8

• 常用中文名：米诺环素
• 常用英文名：Minocycline
• CAS号：10118-90-8
• 分子式：C₂₃H₂₇N₃O₇
• 分子量：457.476
• 相关类别： 原料药 抗生素类药物 四环素类药
• 发布时间：2018-07-26 18:29:35
• 更新时间：2024-01-02 14:12:47
• 米诺环素是一种口服活性、强效和BBB渗透的半合成四环素抗生素。米诺环素是一种缺氧诱导因子(HIF)-1α抑制剂。米诺环素具有抗癌、抗炎和谷氨酸拮抗作用。米诺环素可减少谷氨酸神经传递,并具有神经保护和抗抑郁作用。米诺环素通过与细菌核糖体的30S亚单位结合抑制细菌蛋白质合成,从而产生抑菌作用[1][2][3][4][5][6][7]。

名称

• 中文名: 米诺环素
• 英文名: minocycline
• 中文别名: 4,7-双(二甲氨基)-1,4,4a,5,5a,6,11,12a-八氢-3,10,12,12a-四羟基-1,11-二氧-2-并四苯甲酰胺; 二甲胺四环素; 7-二甲胺基-6-去甲基-6-去氧四环素
• 英文别名: (4S,4aS,5aR,12aS)-4,7-Bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-tetracenecarboximidic acid; Minocyclin; Minocin; 7-dimethylamino-6-demethyl-6-deoxytetracycline; (4S,4aS,5aR,12aS)-4,7-Bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-tetracenecarboxamide; 4S-(4a,4aa,5aa,12aa)-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacene carboxamide; Minocyclinum; [4S-(4a,4aa,5aa,12aa)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide; 2-Naphthacenecarboximidic acid, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-, (4S,4aS,5aR,12aS)-; Apo-Minocycline; (4S,4aS,5aR,12aR)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide; (4S,4aS,5aR,12aS)-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide; 2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-, (4S,4aS,5aR,12aS)-; Minocycline; Arestin; 7-(N,N-dimethylamino)sancycline; Aknemin; Minocyclinum [INN-Latin]; EINECS 237-099-7; Dynacin; Minociclina; MFCD00083669

物化性质

• 密度: 1.6±0.1 g/cm3
• 沸点: 803.3±65.0 °C at 760 mmHg
• 分子式: C₂₃H₂₇N₃O₇
• 分子量: 457.476
• 闪点: 439.6±34.3 °C
• 精确质量: 457.184906
• PSA: 164.63000
• LogP: -0.65
• 外观性状: 亮黄色-橙色非晶形的固体
• 蒸汽压: 0.0±3.0 mmHg at 25°C
• 折射率: 1.718

生物活性

• 描述: 米诺环素是一种口服活性、强效和BBB渗透的半合成四环素抗生素。米诺环素是一种缺氧诱导因子(HIF)-1α抑制剂。米诺环素具有抗癌、抗炎和谷氨酸拮抗作用。米诺环素可减少谷氨酸神经传递,并具有神经保护和抗抑郁作用。米诺环素通过与细菌核糖体的30S亚单位结合抑制细菌蛋白质合成,从而产生抑菌作用[1][2][3][4][5][6][7]。
• 相关类别:
  信号通路 >> 跨膜转运 >> 钙通道
  信号通路 >> 细胞凋亡 >> 细胞凋亡
  研究领域 >> 癌症
  研究领域 >> 心血管疾病
  研究领域 >> 感染
  信号通路 >> 细胞凋亡 >> MDM-2/p53
  研究领域 >> 炎症/免疫
  信号通路 >> 代谢酶/蛋白酶 >> HIF/HIF脯氨酰-羟化酶
  研究领域 >> 代谢疾病
  研究领域 >> 神经疾病
  信号通路 >> 跨膜转运 >> 钾通道
  信号通路 >> 抗感染 >> 细菌
• 靶点:

  L-type calcium channel

• 体外研究: 米诺环素(0-100μM,24-72小时)抑制卵巢癌细胞系(OVCAR-3、SKOV-3和A2780)的增殖和克隆形成活性[3]。米诺环素(0-100μM,24-48小时)通过抑制细胞周期蛋白和抑制DNA掺入来阻止细胞周期[3]。米诺环素(0-100μM,72小时)诱导卵巢癌细胞系中的细胞凋亡[3]。米诺环素显示出直接的神经元保护,这种保护模式可能与线粒体完整性和细胞色素c的保存有关,随后抑制caspase依赖性和caspase非依赖性细胞死亡[2]。米诺环素导致缺氧诱导因子(HIF)-1α的抑制,伴随着p53蛋白水平的上调和AKT/mTOR/p70S6K/4E-BP1途径的失活[6]。细胞增殖试验[3]细胞系：人卵巢癌细胞系(OVCAR-3、SKOV-3和A2780)和原代细胞(HEK-293、HMEC、HUVEC、ATCC)浓度：0、1、10、50和100μM孵育时间：24、48或
• 体内研究: 米诺环素(0-30mg/kg,口服,每日4周)抑制雌性裸鼠OVCAR-3肿瘤生长[3]。在大剂量腹腔注射时,米诺环素(IP)是脑缺血动物模型中的有效神经保护剂[1]。米诺环素(0-40mg/kg,IP,一次)可显著减轻甲基苯丙胺诱导的小鼠过度运动和行为敏化[2]。米诺环素(3和10 mg/kg,静脉注射一次)可有效减少暂时性大脑中动脉闭塞模型(TMCAO)中的梗死面积[1]。二甲胺四环素(3-10 mg/kg,静脉注射一次)的血清水平(3 mg/kg)与标准200 mg剂量后的人体水平相似[1]。米诺环素减轻大鼠缺血诱发的室性心律失常。这种效应可能与PI3K/Akt信号通路、线粒体KATP通道和L型Ca2+通道的激活有关[7]。动物模型：雌性裸鼠(6周龄,每组9只,将OVCAR-3细胞经皮下注射至左侧腹壁
• 参考文献:

  [1]. Xu L, et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004 Apr 26;4:7.

  [2]. Zhang L, et al. Protective effects of minocycline on behavioral changes and neurotoxicity in mice after administration of methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Dec 30;30(8):1381-93.

  [3]. Pourgholami MH, et al. Minocycline inhibits growth of epithelial ovarian cancer. Gynecol Oncol. 2012 May;125(2):433-40.

  [4]. Molina-Hernández M, et al. Antidepressant-like actions of minocycline combined with several glutamate antagonists. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):380-6.

  [5]. Ritchie DJ, et al. A review of intravenous minocycline for treatment of multidrug-resistant Acinetobacter infections. Clin Infect Dis. 2014 Dec 1;59 Suppl 6:S374-80.

  [6]. Ataie-Kachoie P, et al. Minocycline attenuates hypoxia-inducible factor-1α expression correlated with modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro and in vivo studies. Am J Cancer Res. 2015 Jan 15;5(2):575-88.

  [7]. Hu X, Wu B, Wang X, Xu C, He B, Cui B, Lu Z, Jiang H. Minocycline attenuates ischemia-induced ventricular arrhythmias in rats. Eur J Pharmacol. 2011 Mar 11;654(3):274-9.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : QI7630000 CHEMICAL NAME : 2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro -3,10,12,12a- tetrahydroxy-1,11-dioxo- CAS REGISTRY NUMBER : 10118-90-8 LAST UPDATED : 199712 DATA ITEMS CITED : 12 MOLECULAR FORMULA : C23-H27-N3-O7 MOLECULAR WEIGHT : 457.53 WISWESSER LINE NOTATION : L E6 C666 BV FV CU GUTTT&J DQ EQ GMVH HQ IN1&1 ON1&1 RQ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 28 mg/kg/2W-I TOXIC EFFECTS : Brain and Coverings - changes in circulation (hemorrhage, thrombosis, etc.) Sense Organs and Special Senses (Eye) - visual field changes Behavioral - headache TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 343 mg/kg/17W-I TOXIC EFFECTS : Liver - hepatitis (hepatocellular necrosis), diffuse Liver - liver function tests impaired Blood - eosinophilia TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 112 mg/kg/4W-I TOXIC EFFECTS : Liver - liver function tests impaired Skin and Appendages - dermatitis, other (after systemic exposure) Nutritional and Gross Metabolic - body temperature increase TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 100 mg/kg TOXIC EFFECTS : Kidney, Ureter, Bladder - interstitial nephritis Kidney, Ureter, Bladder - proteinuria Kidney, Ureter, Bladder - hematuria TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 1204 mg/kg/86W-I TOXIC EFFECTS : Musculoskeletal - joints TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 730 mg/kg/1Y-I TOXIC EFFECTS : Behavioral - anorexia (human) Gastrointestinal - nausea or vomiting Liver - liver function tests impaired TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3100 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 310 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 140 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intracerebral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 38 mg/kg TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions Behavioral - excitement Musculoskeletal - changes in teeth and supporting structures MUTATION DATA TYPE OF TEST : DNA inhibition TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 3750 ug/L REFERENCE : BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year: 16,127,1983 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3732 No. of Facilities: 13 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 7704 (estimated) No. of Female Employees: 7190 (estimated)

合成路线

13614-98-7 ~% 10118-90-8

文献：WO2010/33939 A1, ; Page/Page column 36 ;

993-50-0 113164-67-3 ~66% 10118-90-8

文献：The Journal of organic chemistry, , vol. 67, # 14 p. 5025 - 5027

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