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氟卡尼 | 54143-55-4

中文名称
氟卡尼
中文别名
N-(2-哌啶基甲基)-2,5-双(2,2,2-三氟乙氧基)苯甲酰胺;氟卡胺;消旋氟卡胺异构体;哌氟酰胺;氟卡尼碱;氟卡律;氟醚卡酰胺
英文名称
flecainide
英文别名
flecainide acetate;N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide;2,5-bis-(2,2,2-Trifluoroethoxy)-n-(2-piperidyl-methyl)-benzamid
氟卡尼化学式
CAS
54143-55-4
化学式
C17H20F6N2O3
mdl
MFCD00864713
分子量
414.348
InChiKey
DJBNUMBKLMJRSA-UHFFFAOYSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    105-1070C
  • 沸点:
    434.9±45.0 °C(Predicted)
  • 密度:
    1.286±0.06 g/cm3(Predicted)
  • 闪点:
    9℃
  • 溶解度:
    可溶于氯仿(少许)、甲醇(少许)
  • 物理描述:
    Solid
  • 碰撞截面:
    192.2 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
  • 保留指数:
    2271;2211.3;2230.5

计算性质

  • 辛醇/水分配系数(LogP):
    3.8
  • 重原子数:
    28
  • 可旋转键数:
    7
  • 环数:
    2.0
  • sp3杂化的碳原子比例:
    0.588
  • 拓扑面积:
    59.6
  • 氢给体数:
    2
  • 氢受体数:
    10

ADMET

代谢
氟卡尼主要代谢为去烷基化的氟卡尼或其去烷基化内酰胺。去烷基化的氟卡尼活性为氟卡尼的20%。这两种代谢物通常以葡萄糖醛酸苷或硫酸盐结合物的形式被检测到。氟卡尼的代谢涉及CYP2D6和CYP1A2的作用。
Flecainide is mainly metabolized to meta-O-dealkylated flecainide or the meta-O-dealkylated lactam of flecainide. Meta-O-dealkylated flecainide has 20% the activity of flecainide. Both of these metabolites are generally detected as glucuronide or sulfate conjugates. Flecainide’s metabolism involves the action of CYP2D6 and CYP1A2.
来源:DrugBank
代谢
肝脏。氟卡尼不经历任何重要的预系统生物转化。两个主要的尿代谢物是代谢-O-去烷基化氟卡尼(活性,但效力大约为原来的五分之一)和氟卡尼的代谢-O-去烷基化内酰胺(非活性代谢物)。口服给药后吸收几乎完全。消除途径:在健康受试者中,单次口服剂量的约30%(范围,10%至50%)以未改变药物的形态从尿液中排出。尿液中还发现了几个次要代谢物(剂量的一小部分,3%或更少);只有5%的口服剂量从粪便中排出。在患者中,两个主要代谢物的游离(未结合)血浆平非常低(小于0.05微克/毫升)。 半衰期:20小时(范围12-27小时)
Hepatic. Flecainide does not undergo any consequential presystemic biotransformation. The two major urinary metabolites are meta-O-dealkylated flecainide (active, but about one-fifth as potent) and the meta-O-dealkylated lactam of flecainide (non-active metabolite). The absoprtion is nearly complete following oral administration. Hepatic. Flecainide does not undergo any consequential presystemic biotransformation. The two major urinary metabolites are meta-O-dealkylated flecainide (active, but about one-fifth as potent) and the meta-O-dealkylated lactam of flecainide (non-active metabolite). Route of Elimination: In healthy subjects, about 30% of a single oral dose (range, 10 to 50%) is excreted in urine as unchanged drug. Several minor metabolites (3% of the dose or less) are also found in urine; only 5% of an oral dose is excreted in feces. In patients, free (unconjugated) plasma levels of the two major metabolites are very low (less than 0.05 ug/mL). Half Life: 20 hours (range 12-27 hours)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 毒性总结
盐酸氟卡尼是一种抗心律失常药,它通过作用于心脏细胞的通道来发挥其抗心律失常的作用。它绑定到电压门控通道上,并通过抑制启动和传导冲动所需的离子流动来稳定细胞膜。这样可以降低心室的兴奋性,并在舒张期间增加心室的刺激阈值。
Flecainide acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. Flecainide is a sodium channel blocker, binding to voltage gated sodium channels. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
  • 肝毒性
在临床试验中,氟卡尼与血清转酶和碱性磷酸酶升高的低发生率有关。尽管广泛使用,氟卡尼与明显肝损伤的病例联系非常罕见。典型的表现是在开始使用氟卡尼后1到6周内出现胆汁淤积性肝炎。此外,有报道称在开始使用氟卡尼后1到3天内发生急性肝损伤,血清转平显著但短暂升高,碱性磷酸酶仅有轻微增加,但这实际上可能代表充血性心力衰竭和缺血性肝炎的急性加重,由于氟卡尼的致心律失常作用。在所有情况下,肝损伤都是自限性的。免疫过敏和自身免疫特征并未出现。
In clinical trials, flecainide was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Despite wide scale use, flecainide has only rarely been linked to cases of clinically apparent liver injury. The typical presentation is with a cholestatic hepatitis arising within 1 to 6 weeks of starting flecainide. In addition, instances of acute hepatic injury arising within 1 to 3 days of starting flecainide with marked, but short lived elevations in serum aminotransferase levels and minimal increases in alkaline phosphatase have been published, but may actually represent acute worsening of congestive heart failure and ischemic hepatitis due to the proarrhythmic effects of flecainide. In all instances, the liver injury was self limited. Immunoallergic and autoimmune features were not present.
来源:LiverTox
毒理性
  • 药物性肝损伤
化合物:氟卡尼
Compound:flecainide
来源:Drug Induced Liver Injury Rank (DILIrank) Dataset
毒理性
  • 药物性肝损伤
药物性肝损伤标注:低药物性肝损伤关注
DILI Annotation:Less-DILI-Concern
来源:Drug Induced Liver Injury Rank (DILIrank) Dataset
毒理性
  • 药物性肝损伤
严重程度等级:7
Severity Grade:7
来源:Drug Induced Liver Injury Rank (DILIrank) Dataset
吸收、分配和排泄
  • 吸收
口服氟卡尼峰浓度时间为3-4小时,生物利用度为90%。与食物或氢氧化铝抗酸药同服氟卡尼,不会显著影响氟卡尼的吸收。
Oral flecainide has a Tmax of 3-4h and a bioavialability of 90%. Taking flecainide with food or aluminum hydroxide antacids do not significantly affect the absorption of flecainide.
来源:DrugBank
吸收、分配和排泄
  • 消除途径
大约86%的单次口服剂量通过尿液排出,其中42%为未改变的氟卡尼,14%为代谢为-O-去烷基化的氟卡尼,相似数量的-O-去烷基化氟卡尼的内酰胺,大约3%为一种未识别的酸性代谢物,以及小于1%为另外两种未知代谢物。5%通过粪便排出。
Approximately 86% of a single oral dose is eliminated in the urine, with 42% as unchanged flecainide and 14% as meta-O-dealkylated flecainide, a similar amount of the meta-O-dealkylated lactam of flecainide, approximately 3% as an unidentified acid metabolite, and <1% as 2 other unknown metabolites. 5% is eliminated in the feces.
来源:DrugBank
吸收、分配和排泄
  • 分布容积
在8名男性受试者中,平均分布体积为5.0-13.4L/kg。
The average volume of distribution in 8 male subjects is 5.0-13.4L/kg.
来源:DrugBank
吸收、分配和排泄
  • 清除
静脉注射氟卡尼的平均清除率为8名男性受试者的4.6-12.1 mL/min/kg。对于口服氟卡尼,清除率为4-20 mL/min/kg。
The average clearance of intravenous flecainide is 4.6-12.1mL/min/kg in 8 male subjects. For oral flecainide, the clearance was 4-20mL/min/kg.
来源:DrugBank

安全信息

  • 危险等级:
    6.1(b)
  • 危险品标志:
    F,T
  • 安全说明:
    S16,S36/37,S45,S7
  • 危险类别码:
    R11,R23/24/25,R39/23/24/25
  • WGK Germany:
    1,2
  • 危险品运输编号:
    3249
  • 包装等级:
    III
  • 危险类别:
    6.1(b)
  • 危险性防范说明:
    P261,P305+P351+P338
  • 危险性描述:
    H302,H315,H319,H335
  • 储存条件:
    | 冰箱 |

SDS

SDS:ba01e2fb8617b90463bf3c5be53a965d
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制备方法与用途

化学性质
UV最大吸收(乙醇):205、230、300 nm (ε1cm1% 521、219、59)。单乙酸氟卡尼(Flecainide Monoacetate):C₁₇H₂₀F₆N₂O₃·C₂H₄O₂。[54143-56-5]。从异丙醇-异丙醚中结晶得到白色颗粒状物质,熔点为145~147℃。在37℃时溶解度(ng/mL):48.4、乙醇300。

用途
乙酸氟卡尼是一种新型、广谱、高效抗心律失常药物,用于治疗多种类型的心律失常,如室上性心动过速、心房颤动、单源性和多源性室性早搏综合征及对其他抗心律失常药物无效的病例。它是首选药物之一。

氟卡尼属于Vaughn-Williams分类中的IC类抗心律失常药物,是一种心脏通道阻滞剂。推荐用于无器质性心脏病的近期发作房颤患者的药物复律。不良心脏影响包括中等程度的负性肌力作用和抑制所有传导途径。

生产方法
方法1:以2,5-二羟基苯甲酸为原料,经三乙基化后,对2-甲基吡啶进行酰化得酰胺,最后在氧化铂存在下氢化得氟卡尼

方法2:在氮气保护下,在25分钟内滴加10.0g(0.0249 mo1)2,5-双(2,2,2-三氟乙氧基)苯甲酸-2,2,2-三乙酯至28.4g(0.249 mo1)2-氨甲基哌啶中。3小时后,往该粘稠的反应液中加入50ml苯,在45℃下继续搅拌40小时。减压加热浓缩以除去挥发性组分,剩余物冷却固化后进行蒸气蒸馏进一步纯化,过滤并用二氯甲烷萃取。萃取液用饱和氯化钠溶液洗涤、无硫酸干燥,过滤除去干燥剂,在搅拌下往滤液中加入4ml 8.4mol/L氯化氢异丙醇溶液。搅拌2小时后冷却至0℃,过滤收集粗产品,用乙醚洗并真空干燥,然后进行活性炭脱色,并以等量的异丙醇甲醇重结晶得盐酸氟卡尼,熔点为228~229℃。

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

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文献信息

  • CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY
    申请人:Cerulean Pharma Inc.
    公开号:US20130196906A1
    公开(公告)日:2013-08-01
    Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.
    提供了关于使用CDP-治疗剂偶联物治疗疾病或紊乱的方法,例如自身免疫疾病、炎症性疾病、中枢神经系统紊乱、心血管疾病或代谢紊乱。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。
  • JNK INHIBITOR
    申请人:Takeda Chemical Industries, Ltd.
    公开号:EP1484320A1
    公开(公告)日:2004-12-08
    A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula wherein ring A and ring B are each an optionally substituted benzene ring, X is -O-, -N=, -NR3- or -CHR3-, R2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.
    一种含有异喹啉酮骨架或其盐的JNK抑制剂,例如由以下公式表示的化合物: 其中环A和环B分别是可选择取代的苯环,X是-O-,-N=,-NR3-或-CHR3-,R2是酰基,可选择酯化或酯化的羧基,可选择取代的基甲酰基或可选择取代的基等,虚线表示单键或双键,R1是氢原子,可选择取代的碳氢基团,可选择取代的杂环基团等。
  • Nitrogen containing heterocyclic compounds and medicines containing the same
    申请人:——
    公开号:US20040167224A1
    公开(公告)日:2004-08-26
    Compounds represented by the following general formula: 1 (wherein X 1 , X 2 , X 3 and X 4 each independently represent a single bond, C 1-6 alkylene, etc.; A 2 represents optionally substituted phenyl, etc.; A 1 represents an optionally substituted 5- to 7-membered heterocyclic group containing —C(═Q 1 )— (wherein Q 1 represents oxygen, sulfur or ═N—R 11 (wherein R 11 represents hydrogen or C 1-6 alkyl)) and nitrogen, etc.; and Z 1 represents piperidin-diyl, etc.), salts thereof and hydrates of the foregoing.
    由以下一般式表示的化合物: 1 (其中X 1 、X 2 、X 3 和X 4 分别独立表示单键,C 1-6 烷基等;A 2 表示可选择地取代的苯基等;A 1 表示可选择地取代的含有—C(═Q 1 )—的5-至7-成员杂环基团(其中Q 1 表示氧、或═N—R 11 (其中R 11 表示氢或C 1-6 烷基))和氮等;以及Z 1 表示哌啶二基等),以及其盐和上述化合物的合物。
  • [EN] PRODRUGS OF SECONDARY AMINE COMPOUNDS<br/>[FR] PROMÉDICAMENTS DE COMPOSÉS AMINE SECONDAIRES
    申请人:ALKERMES PHARMA IRELAND LTD
    公开号:WO2013088255A1
    公开(公告)日:2013-06-20
    The present invention relates to compounds of Formula (I).
    本发明涉及式(I)的化合物。
  • BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
    申请人:Takeda Chemical Industries, Ltd.
    公开号:EP1422228A1
    公开(公告)日:2004-05-26
    The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.
    本发明提供了一种新型的苯并氮杂环衍生物,其由以下公式表示: 其中,R1是一个5-或6-成员的芳香环,R2是低级烷基团等,Y是可选地取代的亚基,环A和环B是独立地选自一个可选地取代的芳香环,W是公式-W1-X2-W2-(W1和W2是独立地为S(O)m1(m1是0、1或2)等,X2是一个可选地取代的亚烷基团等),其制备方法及其用途。
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同类化合物

(βS)-β-氨基-4-(4-羟基苯氧基)-3,5-二碘苯甲丙醇 (S,S)-邻甲苯基-DIPAMP (S)-(-)-7'-〔4(S)-(苄基)恶唑-2-基]-7-二(3,5-二-叔丁基苯基)膦基-2,2',3,3'-四氢-1,1-螺二氢茚 (S)-盐酸沙丁胺醇 (S)-3-(叔丁基)-4-(2,6-二甲氧基苯基)-2,3-二氢苯并[d][1,3]氧磷杂环戊二烯 (S)-2,2'-双[双(3,5-三氟甲基苯基)膦基]-4,4',6,6'-四甲氧基联苯 (S)-1-[3,5-双(三氟甲基)苯基]-3-[1-(二甲基氨基)-3-甲基丁烷-2-基]硫脲 (R)富马酸托特罗定 (R)-(-)-盐酸尼古地平 (R)-(-)-4,12-双(二苯基膦基)[2.2]对环芳烷(1,5环辛二烯)铑(I)四氟硼酸盐 (R)-(+)-7-双(3,5-二叔丁基苯基)膦基7''-[((6-甲基吡啶-2-基甲基)氨基]-2,2'',3,3''-四氢-1,1''-螺双茚满 (R)-(+)-7-双(3,5-二叔丁基苯基)膦基7''-[(4-叔丁基吡啶-2-基甲基)氨基]-2,2'',3,3''-四氢-1,1''-螺双茚满 (R)-(+)-7-双(3,5-二叔丁基苯基)膦基7''-[(3-甲基吡啶-2-基甲基)氨基]-2,2'',3,3''-四氢-1,1''-螺双茚满 (R)-(+)-4,7-双(3,5-二-叔丁基苯基)膦基-7“-[(吡啶-2-基甲基)氨基]-2,2”,3,3'-四氢1,1'-螺二茚满 (R)-3-(叔丁基)-4-(2,6-二苯氧基苯基)-2,3-二氢苯并[d][1,3]氧杂磷杂环戊烯 (R)-2-[((二苯基膦基)甲基]吡咯烷 (R)-1-[3,5-双(三氟甲基)苯基]-3-[1-(二甲基氨基)-3-甲基丁烷-2-基]硫脲 (N-(4-甲氧基苯基)-N-甲基-3-(1-哌啶基)丙-2-烯酰胺) (5-溴-2-羟基苯基)-4-氯苯甲酮 (5-溴-2-氯苯基)(4-羟基苯基)甲酮 (5-氧代-3-苯基-2,5-二氢-1,2,3,4-oxatriazol-3-鎓) (4S,5R)-4-甲基-5-苯基-1,2,3-氧代噻唑烷-2,2-二氧化物-3-羧酸叔丁酯 (4S,4''S)-2,2''-亚环戊基双[4,5-二氢-4-(苯甲基)恶唑] (4-溴苯基)-[2-氟-4-[6-[甲基(丙-2-烯基)氨基]己氧基]苯基]甲酮 (4-丁氧基苯甲基)三苯基溴化磷 (3aR,8aR)-(-)-4,4,8,8-四(3,5-二甲基苯基)四氢-2,2-二甲基-6-苯基-1,3-二氧戊环[4,5-e]二恶唑磷 (3aR,6aS)-5-氧代六氢环戊基[c]吡咯-2(1H)-羧酸酯 (2Z)-3-[[(4-氯苯基)氨基]-2-氰基丙烯酸乙酯 (2S,3S,5S)-5-(叔丁氧基甲酰氨基)-2-(N-5-噻唑基-甲氧羰基)氨基-1,6-二苯基-3-羟基己烷 (2S,2''S,3S,3''S)-3,3''-二叔丁基-4,4''-双(2,6-二甲氧基苯基)-2,2'',3,3''-四氢-2,2''-联苯并[d][1,3]氧杂磷杂戊环 (2S)-(-)-2-{[[[[3,5-双(氟代甲基)苯基]氨基]硫代甲基]氨基}-N-(二苯基甲基)-N,3,3-三甲基丁酰胺 (2S)-2-[[[[[((1S,2S)-2-氨基环己基]氨基]硫代甲基]氨基]-N-(二苯甲基)-N,3,3-三甲基丁酰胺 (2S)-2-[[[[[[((1R,2R)-2-氨基环己基]氨基]硫代甲基]氨基]-N-(二苯甲基)-N,3,3-三甲基丁酰胺 (2-硝基苯基)磷酸三酰胺 (2,6-二氯苯基)乙酰氯 (2,3-二甲氧基-5-甲基苯基)硼酸 (1S,2S,3S,5S)-5-叠氮基-3-(苯基甲氧基)-2-[(苯基甲氧基)甲基]环戊醇 (1S,2S,3R,5R)-2-(苄氧基)甲基-6-氧杂双环[3.1.0]己-3-醇 (1-(4-氟苯基)环丙基)甲胺盐酸盐 (1-(3-溴苯基)环丁基)甲胺盐酸盐 (1-(2-氯苯基)环丁基)甲胺盐酸盐 (1-(2-氟苯基)环丙基)甲胺盐酸盐 (1-(2,6-二氟苯基)环丙基)甲胺盐酸盐 (-)-去甲基西布曲明 龙蒿油 龙胆酸钠 龙胆酸叔丁酯 龙胆酸 龙胆紫-d6 龙胆紫