膦酰甲酸 | 4428-95-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: 膦酰甲酸
• 中文别名: 膦甲酸
• 英文名称: foscarnet
• 英文别名: foscavir；phosphonoformic acid
• CAS: 4428-95-9
• 化学式: CH₃O₅P
• 分子量: 126.006
• InChiKey: ZJAOAACCNHFJAH-UHFFFAOYSA-N

物化性质

• 沸点：
  490.7±28.0 °C(Predicted)
• 密度：
  2.142±0.06 g/cm3(Predicted)
• 物理描述：
  Solid
• 熔点：
  88.06 °C
• 溶解度：
  In water, 1.0X10+6 mg/L (miscible) at 25 °C (est)
• 蒸汽压力：
  1.62X10-6 mm Hg at 25 °C (est)
• 解离常数：
  pKa = 3.13 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

未代谢。

Not metabolized.

来源:DrugBank

毒理性

• 肝毒性

静脉注射膦甲酸钠治疗与一部分患者中轻至中度的血清ALT（谷丙转氨酶）升高有关，但该药物通常给予患有多器官疾病和可能伴有某种程度肝脏损伤的患者。ALT升高通常无症状，即使在继续使用膦甲酸钠的情况下也会缓解。有单个病例报告显示可能由膦甲酸钠引起的临床明显肝损伤。损伤的模式是胆汁淤积性的，通常在使用膦甲酸钠开始后的几周内出现，但肝损伤的临床特征尚未在任何详细程度上进行描述。

Intravenous foscarnet therapy is associated with mild-to-moderate serum ALT elevations in a proportion of patients, but the drug is usually given to patients with multiorgan disease and conditions that may be associated with some degree of hepatic injury. The ALT elevations are usually asymptomatic and resolve even with continuation of foscarnet. Single case reports of clinically apparent liver injury that were possibly attributable to foscarnet have been reported. The pattern of injury was cholestatic arising within weeks of starting foscarnet but the clinical features of the liver injury have not been described in any detail.

来源:LiverTox

毒理性

• 药物性肝损伤

化合物：膦甲酸钠

Compound:foscarnet

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI标注：模糊的DILI关注

DILI Annotation:Ambiguous DILI-concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重性等级：3

Severity Grade:3

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

不良反应部分

Label Section:Adverse reactions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

口服给药后吸收不良（生物利用度从12%到22%）。

Poorly absorbed after oral administration (bioavailability from 12 to 22%).

来源:DrugBank

吸收、分配和排泄

• 清除

2.13 ± 0.71 毫升/分钟/千克 [患者肾功能正常（肌酐清除率 > 80 毫升/分钟）] 68 ± 8 毫升/分钟/千克 [肌酐清除率为 50-80 毫升/分钟] 34 ± 9 毫升/分钟/千克 [肌酐清除率为 25-49 毫升/分钟] 20 ± 4 毫升/分钟/千克 [肌酐清除率为 10-24 毫升/分钟]

2.13 +/- 0.71 mL/min/kg [patients had normal renal function (CrCl > 80 mL/min] 68 +/- 8 mL/min/kg [CrCl was 50-80 mL/min] 34 +/- 9 mL/min/kg [CrCl was 25-49 mL/min] 20 +/- 4 mL/min/kg [CrCl was 10 - 24 mL/min]

来源:DrugBank

吸收、分配和排泄

这项研究调查了在没有活动性巨细胞病毒感染且上消化道功能正常的15名无症状、人类免疫缺陷病毒血清阳性男性患者中，福斯卡尼特的口服制剂（90毫克/千克体重每日一次[QD][n=6]，90毫克/千克体重每日两次[BID][n=6]，以及180毫克/千克体重QD[n=31]）的药代动力学、绝对生物利用度以及8天内的积累情况。第1天的峰血浆药物浓度（平均值±标准差）分别为46.4±10.8 uM（90毫克/千克QD），45.7±6.9 uM（90毫克/千克BID）和64.9±31.7 uM（180毫克/千克QD），在第8天分别上升至86.2±35.8、78.7±35.2和86.4±25.0 uM。福斯卡尼特静脉给药（90毫克/千克）后的平均峰浓度在血浆中为887.3±102.7 uM（n=13）。血浆中的终末半衰期保持不变，第1天（n=15）平均为5.5±2.2小时，第8天（n=13）为6.6±1.9小时，而静脉给药后为5.7±0.7小时。口服生物利用度分别为9.1%±2.2%（90毫克/千克QD），9.5%±1.7%（90毫克/千克BID）和7.6%±3.7%（180毫克/千克QD）；第8天给药的积累比率分别为2.1±1.1、1.8±0.4和1.7±0.7。口服福斯卡尼特的总24小时尿排泄率平均为7.8%±2.6%（第1天）和13.4%±6.0%（第8天），而静脉给药后为95.0%±4.9%。肾小球滤过率和肌酐清除率保持恒定，整个研究组的福斯卡尼特平均24小时肾清除率分别为96±18 mL/min（第1天），88±13 mL/min（第8天）和103±16 mL/min（静脉给药后）。

The pharmacokinetics, absolute bioavailability, /and/ accumulation over 8 days of an oral formulation of foscarnet (90 mg/kg of body weight once daily [QD] [n = 6], 90 mg/kg twice daily [BID] [n = 6], and 180 mg/kg QD [n = 31) were investigated in 15 asymptomatic, human immunodeficiency virus-seropositive male patients free of active cytomegalovirus infection and with normal upper gastrointestinal function. Peak plasma drug concentrations were (mean +/- standard deviation) 46.4 +/- 10.8 uM (90 mg/kg QD), 45.7 +/- 6.9 uM (90 mg/ kg BID), and 64.9 +/- 31.7 uM (180 mg/kg QD) on day 1 and rose to 86.2 +/- 35.8, 78.7 +/- 35.2, and 86.4 +/- 25.0 uM, respectively, on day 8. The mean peak concentration in plasma following the intravenous administration of foscarnet (90 mg/kg) was 887.3 +/- 102.7 uM (n = 13). The terminal half-life in plasma remained unchanged, averaging 5.5 +/- 2.2 hr on day 1 (n = 15) and 6.6 +/- 1.9 hr on day 8 (n = 13), whereas it was 5.7 +/- 0.7 hr following intravenous dosing. Oral bioavailabilities were 9.1% +/- 2.2% (90 mg/kg QD), 9.5% +/- 1.7% (90 mg/kg BID), and 7.6% +/- 3.7% (180 mg/kg QD); the accumulation ratios on the 8th day of dosing were 2.1 +/- 1.1, 1.8 +/- 0.4, and 1.7 +/- 0.7, respectively. The overall 24-hr urinary excretion of oral foscarnet averaged 7.8% +/- 2.6% (day 1) and 13.4% +/- 6.0% (day 8), whereas it was 95.0% +/- 4.9% after intravenous dosing. The glomerular filtration rate and creatinine clearance remained constant, and the mean 24-hr renal clearances of foscarnet for the entire study group were 96 +/- 18 mL/min (day 1), 88 +/- 13 mL/min (day 8), and 103 +/- 16 mL/min after intravenous dosing.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

六名人类免疫缺陷病毒患者在口服溶液中给予磷丙酸钠，每6小时4000毫克，持续3天，然后进行2天的洗脱期，并连续静脉输注72小时内的16,000毫克/24小时。口服磷丙酸钠后，四名患者的血浆浓度低于33微摩尔/升；两名的偶尔浓度为35至50微摩尔/升。吸收程度在12%至22%之间变化。在静脉输注期间，血浆浓度在75至265微摩尔/升之间。磷丙酸钠的处置呈三相，平均半衰期为0.45、3.3和18小时。排泄数据表明消除是通过肾小管分泌和肾小球过滤。肾清除率为176毫升/分钟/1.73平方米。明显的非肾清除率，40毫升/分钟/1.73平方米，可能反映了磷丙酸钠进入骨骼。输注后两天，累计剂量的10%至28%可能沉积在骨骼中。血清钙水平轻微升高和血清磷酸盐值的改变可能反映了磷丙酸钠在骨骼中的摄取。五名患者出现腹泻（口服）和两名患者出现静脉炎（静脉输注）。

Six patients with human immunodeficiency virus were given foscarnet in oral solution, 4000 mg every 6 hours for 3 days, followed by a washout period for 2 days and continuous intravenous infusion of 16,000 mg/24 hr over 72 hours. After oral foscarnet, plasma concentrations were less than 33 mumol/L in four patients; two had occasional concentrations of 35 to 50 mumol/L. The extent of absorption varied between 12% and 22%. During intravenous infusion, plasma concentrations ranged between 75 and 265 mumol/L. The disposition of foscarnet was triphasic, with mean half-lives of 0.45, 3.3, and 18 hours. Excretion data suggested elimination was by tubular secretion and glomerular filtration. Renal clearance was 176 mL/min 1.73 sq m. The apparent nonrenal clearance, 40 mL/min 1.73 sq m, probably reflects sequestration of foscarnet into bone. Ten percent to 28% of the cumulative dose may have been deposited in bone 2 days after infusion. A slight increase in serum calcium levels and changes in serum phosphate values may reflect the uptake of foscarnet in bone. Five patients had diarrhea (oral) and two had thrombophlebitis (intravenous).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚不清楚夫司卡乃特钠是否经人乳排泄...

It is not known whether foscarnet sodium is excreted in human milk...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2931900090

反应信息

• 作为反应物：
  描述：

  膦酰甲酸 在 magnesium chloride 作用下， 以 水 为溶剂， 生成 CHO₅P^(2-)*Mg⁽²⁺⁾
  参考文献：
  名称：

  膦酰基羧酸在水溶液中的络合性质

  摘要：

  膦酰乙酸 (PAA) 与 Ca2+ 和 Mg2+ 离子配合物的浓度形成常数是在 25°C 的水溶液中通过电位滴定和库仑滴定在不同离子强度下测定的，并外推至 I=0 以获得该离子的热力学值。形成常数。配合物由完全去质子化的 Kf (ML) 和单质子化的 Kf (MHL) 形式的 PAA 阴离子形成。复合物的各自值为：log Kf (CaL)=4.68±0.03，log Kf (CaHL)=2.61±0.08；log Kf (MgL)=5.58±0.09，log Kf (MgHL)=3.0±0.3。去质子化的 Ca2+ 和 Mg2+ PAA 物质的络合焓和熵，由 log Kf (ML) 的温度依赖性确定，为：ΔH0(Ca) =0.6±0.2 kcal-mol-1，ΔS0(Ca)=21.4 ±0.6 cal-mol-1-K-1，ΔH0(Mg)=3.0±0.7 kcal-mol-1，ΔS0(Mg)=35±2

  DOI：

  10.1007/bf00646933
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 alkaline solution 作用下， 生成 膦酰甲酸
  参考文献：
  名称：

  Presumptive sialadenosis in a cat

  摘要：

  A cat was presented with signs associated with enlargement of the mandibular salivary glands. Histological findings were normal, consistent with a diagnosis of sialadenosis, and the cat responded to symptomatic treatment with oral phenobarbitone.

  DOI：

  10.1111/j.1748-5827.2000.tb03158.x
• 作为试剂：
  描述：

  N,N-二乙基-3-噻吩羧酰胺 在 正丁基锂 、 四甲基乙二胺 、 膦酰甲酸 作用下， 生成 1-(3-噻吩基)-1-戊酮 、 苯并[1,2-b:4,5-b']二噻吩-4,8-二酮 、 N,N-diethyl-2-(1,1,1,3,3-pentafluoro-2-hydroxypropan-2-yl)thiophene-3-carboxamide
  参考文献：
  名称：

  Reinecke, Manfred G.; Chen, Lao-Jer, Acta Chemica Scandinavica, 1993, vol. 47, # 3, p. 318 - 322

  摘要：

  DOI：

文献信息

• Phosphonoformic acid esters
  申请人：Astra Lakemedel Aktiebolag

  公开号：US04372894A1

  公开（公告）日：1983-02-08

  A compound of the formula ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are the same or different, and each is selected from the group consisting of hydrogen and phenyl groups of the formula ##STR2## wherein R.sub.4 and R.sub.5 are the same or different and each is selected from the group consisting of hydrogen, halogen, alkyl having 1, 2, or 3 carbon atoms, alkoxy having 1, 2, or 3 carbon atoms, alkoxycarbonyl having 2-7 carbon atoms; and alkylcarbonyl groups having 2-7 carbon atoms; or R.sub.4 and R.sub.5 together from a straight saturated alkylene chain having 3 or 4 carbon atoms and being bound to adjacent positions, i.e. 2,3- or 3,4- in the phenyl ring; provided that one of R.sub.1 and R.sub.2 is a phenyl group of the formula II when R.sub.3 is H; and physiologically acceptable salts and optical isomers thereof; methods for preparation of the compounds, pharmaceutical compositions containing them, and their medicinal use.

  式##STR1##的化合物，其中R.sub.1、R.sub.2和R.sub.3相同或不同，且每个均选自由氢和苯基组成的群，该群的式为##STR2##，其中R.sub.4和R.sub.5相同或不同，每个均选自由氢、卤素、具有1、2或3个碳原子的烷基、具有1、2或3个碳原子的烷氧基、具有2-7个碳原子的烷氧羰基；和具有2-7个碳原子的烷基羰基；或者R.sub.4和R.sub.5一起形成直链饱和的具有3或4个碳原子的烷基链，并与相邻位置即苯环中的2,3-或3,4-相连；前提是当R.sub.3为H时，R.sub.1和R.sub.2中的一个是式II的苯基；以及其生理上可接受的盐和光学异构体；制备这些化合物的方法，含有它们的药物组合物，以及它们的药用。
• Phenethylamine compounds
  申请人：SmithKline Beecham Corporation

  公开号：US05710180A1

  公开（公告）日：1998-01-20

  Substituted phenethylamines of formula (I) useful for treating phosphodiesterase IV related ##STR1## disease states are disclosed herein.

  本文揭示了用于治疗磷酸二酯酶IV相关疾病状态的式(I)的取代苯乙胺。
• Polyoxomolybdates Functionalized with Phosphonocarboxylates
  作者：Ulrich Kortz、Catherine Marquer、René Thouvenot、Martine Nierlich

  DOI：10.1021/ic026140m

  日期：2003.2.24

  The novel, functionalized heteropolymolybdate [(O(2)CCH(2)PO(3))(2)Mo(5)O(15)](6-) (1) has been synthesized and characterized by IR and (31)P NMR spectroscopy and elemental analysis. Single-crystal X-ray analysis was carried out on Rb(4)KNa[(O(2)CCH(2)PO(3))(2)Mo(5)O(15)].H(2)O, which crystallizes in the monoclinic system, space group P2(1)/n, with a = 10.146(2) A, b = 13.704(3) A, c = 20.577(4) A

  新颖的，功能化的杂多钼酸盐[[O（2）CCH（2）PO（3））（2）Mo（5）O（15）]（6-）（1）已合成并通过IR和（31）表征P NMR光谱和元素分析。在Rb（4）KNa [（O（2）CCH（2）PO（3））（2）Mo（5）O（15）]。H（2）O上进行单晶X射线分析在单斜晶系空间群P2（1）/ n中结晶，其中a = 10.146（2）A，b = 13.704（3）A，c = 20.577（4）A，β= 94.88（3）度，并且Z =4。标题多阴离子由五个MoO（6）八面体的环组成，具有四个边缘连接和一个角连接。这种非平面排列被两个膦酰基羧酸酯基团稳定，这两个膦酰基羧酸酯基团通过其膦酸酯官能团结合在环的相对侧上。结果，两个悬垂的臂及其末端羧酸酯基团沿完全相反的方向从钼-氧代构架伸出。1的固态结构基于NMR保留在溶液中。我们还报告了同构衍生物[[O（2）CC（2）H（4）PO（3））
• Use of a compound for enhancing the expression of membrane proteins on the cell surface
  申请人：Freissmuth Michael

  公开号：US20060008454A1

  公开（公告）日：2006-01-12

  The present invention is directed to the use of a compound stimulating deubiquitinating activity in a cell for the manufacture of a medicament for enhancing the expression of integral membrane proteins on the cell surface. Especially, the invention is directed to the use of such compound for the manufacture of a medicament for the treatment of a disease of condition selected from the group consisting of cystic fibrosis, diabetes insipidus, hypercholesterinaemia and long QT-syndrome-2.

  本发明涉及使用一种刺激细胞去泛素化活性的化合物，用于制造一种药物，以增强细胞表面的完整膜蛋白的表达。特别地，本发明涉及使用这种化合物制造一种药物，用于治疗来自囊性纤维化、尿崩症、高胆固醇血症和长QT综合症2等疾病或症状的药物。
• Chemical and Redox Speciation of Uranyl with Three Environmentally Relevant Bifunctional Chelates: Multi-Technique Approach Combined with Theoretical Estimations
  作者：Ashutosh Srivastava、Rama Mohana Rao Dumpala、Pranaw Kumar、Ravi Kumar、Neetika Rawat

  DOI：10.1021/acs.inorgchem.2c01991

  日期：2022.10.3

  Carbon and phosphorous are two primary elements common to the bio-geosphere and are omnipresent in both biotic and abiotic arenas. Phosphonate and carboxylate are considered as building blocks of glyphosate and humic substances and constituents of the cellular wall of bacteria and are the driving functionalities for most of the chemical interactions involving these two elements. Phosphonocarboxylates

  碳和磷是生物地圈共有的两种主要元素，在生物和非生物领域都普遍存在。膦酸盐和羧酸盐被认为是草甘膦和腐殖质物质以及细菌细胞壁的组成部分，并且是涉及这两种元素的大多数化学相互作用的驱动功能。膦酸羧酸盐是两个官能团在一个部分中的组合，是深入研究了解两个官能团与金属离子的化学相互作用的理想模型。磷和碳主要分别以无机/有机磷酸盐和羧酸盐的形式存在于生物地圈中。水污染是铀的一个主要问题，络合剂的存在会改变含水层中的铀浓度。通过密度泛函理论计算对E h -pH 图、配位结构和分子水平的理解进行了解释，以解释铀酰 (UO 2 2+ ) 与三种环境相关的膦酰基羧酸盐的相互作用，即膦酰基甲酸 (PFA)、膦酰基-乙酸（PAA）和膦酰基丙酸（PPA）。UO 2 2+与单质子化形式的三种膦酰基羧酸盐形成 1:1 的配合物，稳定性几乎相同，配合物 [UO 2 (PFAH)]、[UO 2 (PAAH)] 和 [UO 2(PPAH)]