倍他米松磷酸酯 | 360-63-4

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 倍他米松磷酸酯
• 中文别名: 地塞米松磷酸钠EP杂质B；1-(4-苯基环己基)乙胺
• 英文名称: betamethasone-21-phosphate
• 英文别名: betamethasone phosphate；9α-Fluor-16β-methylprednisolon-21-phosphorsaeure；[2-[(8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] dihydrogen phosphate
• CAS: 360-63-4
• 化学式: C₂₂H₃₀FO₈P
• 分子量: 472.448
• InChiKey: VQODGRNSFPNSQE-DVTGEIKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  9

ADMET

代谢

磷酸倍他米松迅速脱酯转化为倍他米松。

Betamethasone phosphate is rapidly de-esterified to betamethasone.

来源:DrugBank

毒理性

• 蛋白质结合

皮质类固醇通常与血浆中的皮质类固醇结合球蛋白和血清白蛋白结合。

Corticosteroids are generally bound to corticosteroid binding globulin and serum albumin in plasma.

来源:DrugBank

吸收、分配和排泄

• 吸收

肌肉注射3毫克醋酸倍他米松和3毫克倍他米松磷酸盐，血药浓度达到33.21 ± 8.71纳克/毫升的倍他米松Cmax，达到峰浓度的时间（Tmax）为1.56 ± 1.32小时，药时曲线下面积（AUC）为506.95 ± 125.03纳克*小时/毫升。

An intramuscular injection of 3mg betamethasone acetate and 3mg betametasone phosphate reaches a betamethasone Cmax 33.21 ± 8.71 ng/mL, with a Tmax of 1.56 ± 1.32 h, and an AUC of 506.95 ± 125.03 ng\*h/mL.

来源:DrugBank

吸收、分配和排泄

• 消除途径

皮质类固醇主要通过尿液排出。

Corticosteroids are eliminated predominantly in the urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

给予3mg醋酸倍他米松和3mg磷酸倍他米松的肌肉注射时，倍他米松的分布体积为226.00 ± 61.64 L。

The volume of distribution of betamethasone in an intramuscular injection of 3mg betamethasone acetate and 3mg betamethasone phosphate is 226.00 ± 61.64 L.

来源:DrugBank

吸收、分配和排泄

• 清除

肌肉注射3毫克醋酸倍他米松和3毫克磷酸倍他米松的倍他米松清除率为12.62 ± 3.45 L/h。

The clearance of betamethasone in an intramuscular injection of 3mg betamethasone acetate and 3mg betamethasone phosphate is 12.62 ± 3.45 L/h.

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  倍他米松磷酸酯 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 以91.8 %的产率得到betamethasone sodium phosphate
  参考文献：
  名称：

  抗炎药倍他米松磷酸钠制备新工艺的开发

  摘要：

  在本文中，我们报告了我们为开发一种新型和改进的抗炎类固醇活性药物成分制剂，即倍他米松磷酸钠所做的努力。从市售的倍他米松开始，合成策略包括 C21 位羟基的甲磺酸化，然后是甲磺酸酯衍生物与二叔丁基磷酸钾的关键磷酸化反应，二叔丁基磷酸酯的水解丁酯中间体在弱酸性条件下，最终成盐。开发的工艺使我们能够以 68% 的总收率在多公斤规模下获得所需的倍他米松磷酸钠 ≥ 99.9% HPLC 纯度。还讨论了工艺的成本效益、杂质分析和材料质量。

  DOI：

  10.1021/acs.oprd.2c00329
• 作为产物：
  描述：

  (8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11,17-dihydroxy-17-(2-iodoacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one 生成 倍他米松磷酸酯
  参考文献：
  名称：

  LI, NAIZHI, E. A., PHARM. IND., 1983, N 9, 1-2

  摘要：

  DOI：

文献信息

• [EN] BORONIC ACID DERIVATIVES<br/>[FR] DÉRIVÉS D'ACIDE BORONIQUE
  申请人：MERCK PATENT GMBH

  公开号：WO2016050358A1

  公开（公告）日：2016-04-07

  Compounds of formula (I) are inhibitors of LMP7 and can be employed, inter alia, for the treatment of an autoimmue disorder or hematological malignancies.

  式(I)的化合物是LMP7的抑制剂，可用于治疗自身免疫性疾病或血液恶性肿瘤，等等。
• SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
  申请人：Ohio State Innovation Foundation

  公开号：US20140155577A1

  公开（公告）日：2014-06-05

  Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.

  揭示了与受保护或未受保护的氨基酸或肽连接的疏水药物的共轭物。所述的共轭物是两性的，可以自组装成纳米管。还描述了包含这些共轭物的纳米管，可以具有高药物载荷并保护药物免受降解或排泄。这些纳米管非常适合向个体输送疏水和不稳定的药物。
• [EN] ATX MODULATING AGENTS<br/>[FR] AGENTS DE MODULATION D'ATX
  申请人：BIOGEN MA INC

  公开号：WO2015188051A1

  公开（公告）日：2015-12-10

  Compounds of formula (I) can modulate the activity of autotaxin (ATX).

  式(I)的化合物可以调节自体税肽酶（ATX）的活性。
• [EN] ALPHA-AMINO BORONIC ACID DERIVATIVES, SELECTIVE IMMUNOPROTEASOME INHIBITORS<br/>[FR] DÉRIVÉS D'ACIDE ALPHA-AMINO BORONIQUE, INHIBITEURS SÉLECTIFS DE L'IMMUNOPROTÉASOME
  申请人：ARES TRADING SA

  公开号：WO2013092979A1

  公开（公告）日：2013-06-27

  The present invention provides compounds of Formula (I) as inhibitors of LMP7 for the treatment of autoimmune and inflammatory diseases. In formula (I), Rb and Rc are independently selected from one another from H or C1-C6-alkyl; whereby Rb and Rc may be linked to form a 5 or 6 membered-ring containing the oxygen atoms to which they are linked; Q denotes Ar, Het or cycloalkyl; R1 R2 independently from each other denotes H, ORa, Hal, C1-C6-alkyl wherein 1 to 5 H atoms may be independently replaced by OH or Hal; Y denotes CR 3R4, preferably CH2 or C(CH3)2; R 3, R4 independently of one another denote H or C1-C6-alkyl; L denotes L1 or L2 or alkyl; n is an integer selected from 0 to 3; L 1 is Q1-CO-M- wherein Q 1 is Ar or Het, preferably, phenyl, naphthyl or pyridine, optionally substituted with 1 to 5 groups independently selected from ORa, Hal, phenyl, and C1-C6-alkyl wherein 1 to 5 H atoms may be independently replaced by OH or Hal; L2 is Q2-M- wherein Q 2 is a fused bicyclic system containing 1 nitrogen atom and 1 to 3 additional groups independently selected from O, S, N, or CO, and wherein at least one of the rings is aromatic whereby the fused bicyclic system is optionally substituted with 1 to 5 groups independently selected from ORa, Hal, phenyl, and C1-C6-alkyl wherein 1 to 5 H atoms may be independently replaced by OH or Hal; or Q 2 is unsaturated or aromatic 5 membered-ring system containing 1 to 3 heteroatoms selected from N, O, S and CO, and optionally substituted with a phenyl ring or pyridine ring whereby phenyl ring and pyridine ring are optionally substituted with 1 to 4 groups independently selected from ORa, Hal, phenyl, and C1-C6-alkyl wherein 1 to 5 H atoms may be independently replaced by OH or Hal; M is a linear or branched alkylene having 1 to 5 carbon atoms wherein 1 or 2 H atoms may be replaced by OR a or a phenyl ring optionally substituted with 1 to 5 groups independently selected from Hal, ORa, and C1-C6-alkyl optionally substituted with 1 to 5 groups independently selected from OH, and Hal; or M denotes a cycloalkylene having 3 to 7 carbon atoms; or M denotes a thiazolidinyl group; R a is H or C1-C6-alkyl wherein 1 to 5 H atom may be independently replaced by OH or Hal; Ar denotes a 6 membered-aromatic carbocyclic ring optionally fused with another carbocyclic saturated, unsaturated or aromatic ring having 5 to 8 carbon atoms; Het denotes a 5- or 6-membered saturated, unsaturated or aromatic heterocyclic ring having 1 to 3 heteroatoms independently selected from N, N+O-, O, S, SO, and SO 2, and optionally fused with another saturated, unsaturated or aromatic ring having 5 to 8 atoms and optionally containing 1 to 3 heteroatoms selected from N, O, and S; Hal denotes CI, Br, I of F; preferably CI or F.

  本发明提供了化合物的公式（I）作为LMP7的抑制剂，用于治疗自身免疫和炎症性疾病。在公式（I）中，Rb和Rc分别独立地从H或C1-C6-烷基中选择；其中Rb和Rc可以连接形成一个含有它们连接的氧原子的5或6元环；Q表示Ar，Het或环烷基；R1和R2彼此独立地表示H，ORa，Hal，C1-C6-烷基，其中1到5个H原子可以独立地被OH或Hal替换；Y表示CR 3R4，优选CH2或C(CH3)2；R3，R4彼此独立地表示H或C1-C6-烷基；L表示L1或L2或烷基；n是从0到3选择的整数；L1是Q1-CO-M-，其中Q1是Ar或Het，优选苯基，萘基或吡啶基，可选地取代为1到5个从ORa，Hal，苯基和C1-C6-烷基中独立选择的基团，其中1到5个H原子可以独立地被OH或Hal替换；L2是Q2-M-，其中Q2是含有1个氮原子和1到3个额外基团的融合双环系统，独立选择自O，S，N或CO，其中至少一个环是芳香环，融合双环系统可选地取代为1到5个从ORa，Hal，苯基和C1-C6-烷基中独立选择的基团，其中1到5个H原子可以独立地被OH或Hal替换；或Q2是不饱和或芳香的含有1到3个从N，O，S和CO中选择的杂原子的5元环系统，并可选地取代为苯环或吡啶环，其中苯环和吡啶环可选地取代为1到4个从ORa，Hal，苯基和C1-C6-烷基中独立选择的基团，其中1到5个H原子可以独立地被OH或Hal替换；M是具有1到5个碳原子的线性或支链烷基，其中1或2个H原子可以被ORa或可选地取代为1到5个从Hal，ORa和C1-C6-烷基中独立选择的基团，可选地取代为1到5个从OH和Hal中独立选择的基团；或M表示具有3到7个碳原子的环烷基；或M表示噻唑烷基；Ra是H或C1-C6-烷基，其中1到5个H原子可以独立地被OH或Hal替换；Ar表示一个6元芳香碳环，可选地与另一个含有5到8个碳原子的碳环饱和、不饱和或芳香环融合；Het表示一个含有1到3个从N，N+O-，O，S，SO和SO2中独立选择的杂原子的5或6元饱和、不饱和或芳香杂环，可选地与另一个含有5到8个原子的饱和、不饱和或芳香环融合，并可选地含有1到3个从N，O和S中选择的杂原子；Hal表示CI，Br，I或F；优选CI或F。
• [EN] 5-(BIPHENYL-4-YL)-3-PHENYL-1,2,4-OXADIAZOLYL DERIVATIVES AS LIGANDS ON THE SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTORS<br/>[FR] DÉRIVÉS DE 5-(BIPHÉNYL-4-YL)-3-PHÉNYL-1,2,4-OXADIAZOLYLE COMME LIGANDS SUR LES RÉCEPTEURS AU SPHINGOSINE-1-PHOSPHATE (S1P)
  申请人：MERCK SERONO SA

  公开号：WO2012004287A1

  公开（公告）日：2012-01-12

  The present invention provides compounds of Formula (I), as selective S1 P1 inhibitors, as well as their use for treating multiple sclerosis and other diseases.

  本发明提供了化合物I的公式，作为选择性S1 P1抑制剂，以及它们用于治疗多发性硬化症和其他疾病的用途。