248281-84-7

• 常用中文名：拉喹莫德
• 常用英文名：Laquinimod
• CAS号：248281-84-7
• 分子式：C₁₉H₁₇ClN₂O₃
• 分子量：356.80
• 相关类别： 信号通路 NF-κB信号通路 NF-κB
• 发布时间：2018-09-17 18:43:12
• 更新时间：2024-01-07 09:08:08
• Laquinimod是一种有效的免疫调节剂,可预防中枢神经系统的神经变性和炎症。

名称

• 中文名: 拉喹莫德
• 英文名: 5-chloro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenylquinoline-3-carboxamide
• 英文别名: 5-Chloro-N-Et-4-hydroxy-1-methyl-2-oxo-N-Ph-1,2-dihydroquinoline-3-carboxamide; 5-chloro-N-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinolinecarboxamide; 5-CHLORO-N-ETHYL-4-HYDROXY-1-METHYL-2-OXO-N-PHENYL-1,2-DIHYDROQUINOLINE-3-CARBOXAMIDE; 5-chloro-n-ethyl-2-hydroxy-1-methyl-4-oxo-n-phenyl-1,4-dihydroquinoline-3-carboxamide; 5-Chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid ethyl-phenyl-amide; Lanquinimod; Laquinimod; 2-{[(2,4-Dichlorophenoxy)acetyl]amino}ethyl thiocyanate; N-ethyl-N-phenyl-1,2-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxoquinoline-3-carboxamide; Thiocyanic acid, 2-[[2-(2,4-dichlorophenoxy)acetyl]amino]ethyl ester; 5-chloro-1,2-dihydro-N-ethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinoline carboxamide; 5-Chloro-4-hydroxy-1-methyl-2-oxo-N-ethyl-N-phenyl-1,2-dihydroquinoline-3-carboxamide; N-ethyl-N-phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide; [14C]-Laquinimod; ABR-215062

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 546.0±50.0 °C at 760 mmHg
• 分子式: C₁₉H₁₇ClN₂O₃
• 分子量: 356.80
• 闪点: 284.0±30.1 °C
• PSA: 87.42000
• LogP: 2.79
• 外观性状: 固体;White to Light yellow powder to crystal
• 蒸汽压: 0.0±1.5 mmHg at 25°C
• 折射率: 1.587
• 储存条件: 存放于惰性气体之中;避免空气

生物活性

• 描述: Laquinimod是一种有效的免疫调节剂,可预防中枢神经系统的神经变性和炎症。
• 相关类别:
  信号通路 >> NF-κB信号通路 >> NF-κB
  研究领域 >> 炎症/免疫
• 靶点:

  NF-κB

• 体外研究: 拉喹莫德逆转EAE并抑制致病性T细胞免疫应答。拉喹莫德逆转RR-EAE并通过对骨髓APC的直接作用抑制炎性T细胞应答。拉喹莫德改变骨髓APC亚群并抑制髓鞘特异性T细胞的Th1和Th17极化。拉喹莫德诱导的II型(M2)单核细胞逆转建立的EAE [1]。拉喹莫德调节健康供体的B细胞的表型。拉喹莫德调节与RRMS患者的B细胞中的调节能力相关的标志物的表达。拉喹莫德降低CD4 + T细胞中IFNγ细胞因子的表达[2]。
• 体内研究: 拉喹莫德治疗抑制供体髓鞘特异性T细胞将EAE转移至幼稚受体小鼠。体内拉喹莫德治疗改变骨髓抗原呈递细胞亚群(APC),包括CD11c + CD11b + CD4 +树突状细胞(DC)的减少和CD11bhiGr1hi单核细胞的升高[1]。
• 细胞实验: 将来自拉喹莫德或媒介物处理的小鼠的纯化的CD11b +细胞与从拉喹莫德或媒介物处理的2D2小鼠和抗原（MOGp35-55,20μg/ mL）分离的幼稚CD4 +细胞一起培养。将细胞以0.25×10 6个细胞/ mL的浓度在96孔微量滴定板中培养。培养基由RPMI 1640组成，补充L-谷氨酰胺（2 mM），丙酮酸钠（1 mM），青霉素（100 U / mL），链霉素（0.1 mg / mL），2-巯基乙醇（5×10-5 M）和10％（v / v）胎牛血清。将细胞温育48小时，并在收获前用每孔1μCi的[3H] - 胸苷脉冲18小时。
• 动物实验: 7至10周龄雌性C57BL / 6，DBA / 1或SJL / J小鼠分别在完全弗氏佐剂中皮下注射50μgMOGp35-55,50μgrMOG或100μgPLPp139-151。免疫后和2天后，小鼠腹膜内（ip）接受200ng（C57BL / 6）或100ng（SJL / J）百日咳毒素。对于过继转移，如上所述免疫供体SJL / J小鼠并每天用拉喹莫德或载体处理。 10天后，分离来自引流淋巴结和脾的细胞，再刺激48小时（20μg/ mL PLP p139-151），并腹膜内注射到幼稚SJL / J受体（每只小鼠107个细胞）中。每天观察动物并评估临床评分如下：0，无迹象; 1，尾音减少; 2，轻度单发或下肢轻瘫; 3，严重的瘫痪; 4，截瘫和/或quadraparesis; 5，垂死或死亡。
• 参考文献:

  [1]. Schulze-Topphoff, Ulf., et al. Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity. PLoS One (2012), 7(3), e33797.

  [2]. Toubi E, et al. Laquinimod modulates B cells and their regulatory effects on T cells in Multiple Sclerosis. J Neuroimmunol. 2012 Oct 15;251(1-2):45-54.

  [3]. Brück W, et al. Reduced astrocytic NF-κB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol. 2012 Sep;124(3):411-24.

MSDS

Material Safety Data Sheet Section1. Identification of the substance Product Name: Laquinimod Synonyms: Section2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section3. Composition/information on ingredients. Ingredient name:Laquinimod CAS number:248281-84-7 Section4. First aid measures Skin contact:Immediately wash skin with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. If irritation persists, seek medical attention. Eye contact:Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical attention. Inhalation:Remove to fresh air. In severe cases or if symptoms persist, seek medical attention. Ingestion:Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention. Section5. Fire fighting measures In the event of a fire involving this material, alone or in combination with other materials, use dry powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus should be worn. Section6. Accidental release measures Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national standards. Respiratory precaution:Wear approved mask/respirator Hand precaution:Wear suitable gloves/gauntlets Skin protection:Wear suitable protective clothing Eye protection:Wear suitable eye protection Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container for disposal. See section 12. Environmental precautions: Do not allow material to enter drains or water courses. Section7. Handling and storage Handling:This product should be handled only by, or under the close supervision of, those properly qualified in the handling and use of potentially hazardous chemicals, who should take into account the fire, health and chemical hazard data given on this sheet. Store in closed vessels. Storage: Section8. Exposure Controls / Personal protection Engineering Controls: Use only in a chemical fume hood. Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles. General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse. Section9. Physical and chemical properties Appearance:Not specified Boiling point:No data No data Melting point: Flash point:No data Density:No data Molecular formula:C19H17ClN2O3 Molecular weight:356.8 Section10. Stability and reactivity Conditions to avoid: Heat, flames and sparks. Materials to avoid: Oxidizing agents. Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride. Section11. Toxicological information No data. Section12. Ecological information No data. Section13. Disposal consideration Arrange disposal as special waste, by licensed disposal company, in consultation with local waste disposal authority, in accordance with national and regional regulations. Section14. Transportation information Non-harzardous for air and ground transportation. Section15. Regulatory information No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302, or have known CAS numbers that exceed the threshold reporting levels established by SARA Title III, Section 313. SECTION 16 - ADDITIONAL INFORMATION N/A

安全

• 危害码 (欧洲): T+
• 海关编码: 2933790090

合成路线

上下游产品

上游产品  9
103-69-5 335640-50-1 637027-41-9 20829-96-3
2148-56-3 40707-01-5 248282-10-2 142613-14-7
118081-77-9
下游产品  1
637027-41-9

海关

海关编码	2933790090
中文概述	2933790090 其他内酰胺. 增值税率:17.0% 退税率:9.0% 监管条件:无 最惠国关税:9.0% 普通关税:20.0%
申报要素	品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期
Summary	2933790090. other lactams. VAT:17.0%. Tax rebate rate:9.0%. . MFN tariff:9.0%. General tariff:20.0%