CAS: 843663-66-1; (1R,2S)-1-(6-Bromo-2-Methoxyquinolin-3-yl)-4-(Dimethylamino)-2-(Naphthalen-1-yl)-1-Phenylbutan-2-Ol

• 英文名称(1R,2S)-1-(6-Bromo-2-Methoxyquinolin-3-yl)-4-(Dimethylamino)-2-(Naphthalen-1-yl)-1-Phenylbutan-2-Ol
• 中文名称6-溴-α-[2-(二甲基氨基)乙基]-2-甲氧基-α-1-萘基-β-苯基-3-喹啉乙醇
• IUPAC名称(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol
• 其它别名Bedaquiline; Bedaquilina; Bedaquilinum; Bedaquiline [usan:Inn]; (1R,2S)-1-(6-Bromo-2-Methoxyquinolin-3-yl)-4-(Dimethylamino)-2-(Naphthalen-1-yl)-1-P
• CAS编号843663-66-1
• MFCD编号:MFCD14635354
• EINECS号:831-215-5
• 分子式:C32H31BrN2O2
• 分子量:555.5
• 产品CID: 1832154
• 同类组份化合物CAS843663-66-1 (free base)845533-86-0 (fumarate)Unknown (HCl)
• 产品分类原料药 → 人工合成抗感染类药 → 抗结核麻风分支杆菌类药

• 相似结构搜索
• InChIKey: QUIJNHUBAXPXFS-XLJNKUFUSA-N
• InChI=1S/C32H31BrN2O2/c1-35(2)19-18-32(36,28-15-9-13-22-10-7-8-14-26(22)28)30(23-11-5-4-6-12-23)27-21-24-20-25(33)16-17-29(24)34-31(27)37-3/…
• 计算化学: 氢键受体数4.0氢键供体数1.0可旋转键数8.0

物理性质

• 熔点104 °C
• 沸点702.7±60.0 °C at 760 mmHg
• 闪点378.8±32.9 °C
• 密度1.3±0.1 g/cm3
• pKa:13.05±0.29(预测)
• PSA:36.36
• LogP:7.59
• 折射率1.666
• 蒸汽压0.0±2.3 mmHg at 25°C
• 溶解性Soluble In DMSO (10 mg/mL)
• 外观形态白色固体
• 储存条件室温
• 产品应用该化合物用于用GC-或LC-质谱测量法量化BEDAQUILINE的内部标准.

MSDS等安全信息

• GHS象形图
• GHS符号GHS06 & GHS08 & GHS09;
  注释: Skull and crossbones & Health hazard & Environment
• 危险类别急性毒性 类别3(经口)
  特定目标器官毒性-重复接触 类别2
  水生急性毒性 类别1
  水生慢性毒性 类别1
• 警示词Danger(危险)
• 危险描述H301 |吞咽会中毒.
  H373 |长期或反复接触可能损害器官.
  H400 |对水生生物毒性极大.
  H410 |对水生生物毒性极大并具有长期持续影响.
• 防范说明P273-P391-P501-P264-P270-P301+P310-P321-P330-P405-P501-P273-P391-P501-P260-P314-P501
• 安全声明IDENTIFICATION AND USE: Bedaquiline is a white solid. It is used as a antitubercular medication. HUMAN EXPOSURE AND TOXICITY: An increased risk of death was observed in patients receiving bedaquiline in a placebo-controlled clinical trial. In this study, there were 9 deaths in bedaquiline-treated patients; one death occurred during the 24 weeks of bedaquiline therapy and the median time to death for the other 8 patients was 329 days after the last dose of bedaquiline. Five of the 9 deaths in bedaquiline-treated patients and both deaths in placebo-treated patients were related to tuberculosis. The explanation for the imbalance in deaths in this study is not known; no correlation was demonstrated between death and sputum culture conversion, relapse, susceptibility to other antituberculosis drugs, HIV status, or disease severity. Bedaquiline and the M2 metabolite are cationic amphiphilic substances and induce phospholipidosis. The cells of the monocytic phagocytic system are affected in all species. Data from in vitro studies using human monocyte cell-line indicated that the phospholipidogenic potential was highest for the M2 metabolite followed by M3 and the parent compound. ANIMAL STUDIES: In mouse and rat, single oral doses of 800 mg/kg produced lethality preceded by signs of general toxicity. Mortalities in mouse and dog after single and repeated doses were principally attributed to skeletal muscle/myocardial degeneration and/or pancreatitis. Bedaquiline was not carcinogenic in rats up to the maximum tolerated dose of 10 mg/kg/day. In embryofetal toxicity studies conducted in rat and rabbit bedaquiline appeared to have no adverse effects on the embryonal development and the incidence of variations and malformations in fetuses in bedaquiline groups were within normal ranges. Exposure to bedaquiline and the M2 metabolite in rat at the high dose was considerable (up to 6-7 times higher compared with expected human exposure), while in rabbit a maximum exposure ratio of 2 were achieved. However, in rabbit the high dose of 100 mg/kg caused deaths, one abortion and increases in pre and postimplantation losses. Bedaquiline had no effect on fertility in females up to the highest dose tested, 24 mg/kg. Male fertility appeared to be decreased with a NOAEL of 5 mg/kg. No mutagenic or clastogenic effects were detected in the in vitro non-mammalian reverse mutation (Ames) test, in vitro mammalian (mouse lymphoma) forward mutation assay and an in vivo mouse bone marrow micronucleus assay.

欧盟法规

上下游产品

合成工艺路线路线简述

• 654653-93-7 = 843663-66-1 + 857086-93-2 + 654653-92-6
  反应条件:1.1 Reagents: (-)-1,1′-Binaphthyl-2,2′-Diyl Hydrogen Phosphate Solvents: Acetone; 1 H,Reflux1.2 Reagents: Potassium Carbonate Solvents: Toluene,Water; 30 Min,80 °C
  标题:A Highly Efficient Way To Recycle Inactive Stereoisomers Of Bedaquiline Into Two Previous Intermediates Via Base-Catalyzed Csp3-Csp3 Bond Cleavage
  作者:Kong,De-Long; Et Al
  参考文献:Chinese Chemical Letters 日期:2015 卷标:26(6) 页码:790-792]
  
  654655-69-3 + 10320-49-7 = 843663-66-1 + 857086-93-2 + 654653-92-6
  反应条件:1.1 Reagents: Lithium Diisopropylamide Solvents: Tetrahydrofuran; -78 °C; 1 H,-78 °C1.2 Solvents: Tetrahydrofuran; 1 H,-78 °C; 12 H,-78 °C; -78 °C -> -40 °C1.3 Reagents: Water; 30 Min,-40 °C2.1 Reagents: (-)-1,1′-Binaphthyl-2,2′-Diyl Hydrogen Phosphate Solvents: Acetone; 1 H,Reflux2.2 Reagents: Potassium Carbonate Solvents: Toluene,Water; 30 Min,80 °C
  标题:A Highly Efficient Way To Recycle Inactive Stereoisomers Of Bedaquiline Into Two Previous Intermediates Via Base-Catalyzed Csp3-Csp3 Bond Cleavage
  作者:Kong,De-Long; Et Al
  参考文献:Chinese Chemical Letters 日期:2015 卷标:26(6) 页码:790-792]
  
  110-17-8 + 843663-66-1 = 843663-66-1
  反应条件:1.1 Reagents: Sodium Bicarbonate Solvents: Dichloromethane; Rt
  标题:Crystal Structures Of Salts Of Bedaquiline
  作者:Okezue,Mercy; Et Al
  参考文献:Acta Crystallographica 日期:2020 卷标:76(11) 页码:1010-1023]
  
  1229443-13-3 = 843663-66-1
  反应条件:1.1 Reagents: 4-(Dimethylamino)Pyridine Solvents: Pyridine; 16 H,Rt1.2 Reagents: Water; Rt2.1 Solvents: Dimethylformamide,Water; 10 H,40 °C2.2 Reagents: Water
  标题:Catalytic Asymmetric Synthesis Of R207910
  作者:Saga,Yutaka; Et Al
  参考文献:Journal Of The American Chemical Society 日期:2010 卷标:132(23) 页码:7905-7907]
  
  1229443-16-6 = 843663-66-1
  反应条件:1.1 Solvents: Dimethylformamide,Water; 10 H,40 °C1.2 Reagents: Water
  标题:Catalytic Asymmetric Synthesis Of R207910
  作者:Saga,Yutaka; Et Al
  参考文献:Journal Of The American Chemical Society 日期:2010 卷标:132(23) 页码:7905-7907]
  
  654655-80-8 = 843663-66-1
  反应条件:1.1 Rt
  标题:Synthesis Of Related Substance Of Bedaquiline Fumarate
  作者:Pan,Lin-Yu; Et Al
  参考文献:Zhongguo Yaowu Huaxue Zazhi 日期:2014 卷标:24(6) 页码:441-444]
  
  654653-93-7 = 843663-66-1 [标题:Reaction Conditions
  标题:Asymmetric Synthesis Of Bedaquiline Based On Bimetallic Activation And Non-Covalent Interaction Promotion Strategies
  作者:Gao,Feng; Et Al
  参考文献:Science China: Chemistry 日期:2022 卷标:65(10) 页码:1968-1977

海关参考信息

• 2902600000-乙苯
  2902700000-异丙基苯
  2902902000-精萘
  2905122000-异丙醇
• 💡 提示：海关信息按照顺序优先匹配，如需确认的海关信息，请参考相关资料。
• 详情请参考：📖 海关编码查询和海关进出口税则

其他信息查阅

• ➥ 象形图和危险代码
• ➥ 防范代码详解
• ➥ 危险代码说明
• ➥ Globally Harmonized System
• ➥ REACH监管