S) FTY720磷酸酯 | 402616-26-6

• 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 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 中文名称: S) FTY720磷酸酯
• 中文别名: S)FTY720磷酸酯
• 英文名称: (S)-fingolimod phosphate
• 英文别名: (S)-FTY720P；(S)-2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol mono(dihydrogenphosphate) ester；(2S)-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol monophosphorylated form；(S)-FTY720-phosphate；(S)-FTI720-P；FTY 720(S)-P；(S) FTY720 Phosphate；[(2S)-2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate
• CAS: 402616-26-6
• 化学式: C₁₉H₃₄NO₅P
• 分子量: 387.456
• InChiKey: LRFKWQGGENFBFO-IBGZPJMESA-N

物化性质

• 熔点：
  184-186°C
• 沸点：
  584.2±60.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为0.3mg/mL，澄清（加热）

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  26
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  6

安全信息

• 储存条件：
  -20°C，密闭保存，干燥环境中存放

制备方法与用途

生物活性

FTY720 (S)-磷酸盐是一种S1P受体1（S1PR1）激动剂，适用于急性肺损伤等急性炎症的研究。

靶点

• S1PR1

体外研究

FTY720 (S)-磷酸盐是S1PR1的激动剂。在浓度为1 µM时，FTY720 (S)-磷酸盐能够维持S1PR1蛋白表达，并通过激活S1PR1增强人肺动脉内皮细胞屏障功能，但不会诱导S1PR1的泛素化。此外，在浓度范围从0.01 µM到50 µM时，FTY720 (S)-磷酸盐还能减少β- Arrestin对S1PR1的募集。

体内研究

在小鼠中，以0.5 mg/kg剂量（腹腔注射）给予FTY720 (S)-磷酸盐能够保护肺部免受博莱霉素诱导的急性肺损伤，并减轻博莱霉素受伤小鼠的肺组织白细胞浸润。

反应信息

• 作为反应物：
  描述：

  S) FTY720磷酸酯 、 邻苯二甲醛 在 氢氧化钾 、 乙二胺四乙酸 、 硼酸 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 phosphoric acid mono[(S)-2-hydroxymethyl-4-(4-octylphenyl)-2-(1-oxo-1,3-dihydroisoindol-2-yl)butyl]ester
  参考文献：
  名称：

  Novel Immunomodulator FTY720 Is Phosphorylated in Rats and Humans To Form a Single Stereoisomer. Identification, Chemical Proof, and Biological Characterization of the Biologically Active Species and Its Enantiomer

  摘要：

  In vivo phosphorylation. of FTY720 (1) in rats and humans resulted exclusively in the biologically active (S)-configured enantiomer, which was proven by an ex vivo o-phthaldialdehyde derivatization protocol especially elaborated for phosphates of 1. Starting from the prochiral amino alcohol 1, racemic and enantiomerically pure phosphates of 1 were synthesized. Pure enantiomers were obtained after purification of a partially protected key intermediate on an enantioselective support. The absolute stereochemistry was determined by X-ray diffraction.

  DOI：

  10.1021/jm050242f
• 作为产物：
  描述：

  2-氨基-2-[2-(4-辛基苯基)乙基]-1,3-丙二醇 在 palladium on activated charcoal 四氮唑 、 lithium hydroxide 、 sodium hydroxide 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 93.0h， 生成 S) FTY720磷酸酯
  参考文献：
  名称：

  Novel Immunomodulator FTY720 Is Phosphorylated in Rats and Humans To Form a Single Stereoisomer. Identification, Chemical Proof, and Biological Characterization of the Biologically Active Species and Its Enantiomer

  摘要：

  In vivo phosphorylation. of FTY720 (1) in rats and humans resulted exclusively in the biologically active (S)-configured enantiomer, which was proven by an ex vivo o-phthaldialdehyde derivatization protocol especially elaborated for phosphates of 1. Starting from the prochiral amino alcohol 1, racemic and enantiomerically pure phosphates of 1 were synthesized. Pure enantiomers were obtained after purification of a partially protected key intermediate on an enantioselective support. The absolute stereochemistry was determined by X-ray diffraction.

  DOI：

  10.1021/jm050242f

文献信息

• Phosphate derivatives as immunoregulatory agents
  申请人：——

  公开号：US20020091105A1

  公开（公告）日：2002-07-11

  Immunoregulatory compounds are disclosed of the formula: 1 and 2 as well as the pharmaceutically acceptable salts and hydrates thereof, are disclosed. The compounds are useful for treating immune mediated diseases and conditions, such as bone marrow, organ and tissue transplant rejection. Pharmaceutical compositions and methods of use are included.

  揭示了具有以下式子的免疫调节化合物：1和2以及其药用盐和水合物。这些化合物可用于治疗免疫介导的疾病和状况，如骨髓、器官和组织移植排斥。包括药物组成和使用方法。
• Synthesis, stereochemical determination and biochemical characterization of the enantiomeric phosphate esters of the novel immunosuppressive agent FTY720
  作者：Jeffrey J. Hale、Lin Yan、William E. Neway、Richard Hajdu、James D. Bergstrom、James A. Milligan、Gan-Ju Shei、Gary L. Chrebet、Rosemary A. Thornton、Deborah Card、Mark Rosenbach、HughRosen、Suzanne Mandala

  DOI：10.1016/j.bmc.2004.07.020

  日期：2004.9

  The novel immunosuppressive agent FTY720 (1) is phosphorylated in vivo in a variety of species yielding an active metabolite that is an agonist of four of the five known G-protein-coupled sphingosine-1-phosphate (S1P) receptors. A synthesis amenable to producing gram quantities of the stereoisomeric phosphate esters, a determination of their absolute stereochemistry via an enantioselective synthesis

  新型免疫抑制剂FTY720（1）在多种物种中都体内磷酸化，产生一种活性代谢产物，该代谢产物是5种已知的G蛋白偶联1鞘氨醇（S1P）受体中的4种的激动剂。据报道，该合成方法适于产生克量的立体异构磷酸酯，通过对映选择性合成确定其绝对立体化学，并将其表征为S1P受体激动剂和拮抗剂。
• Asymmetric synthesis and biological evaluation of the enantiomeric isomers of the immunosuppressive FTY720-phosphate
  作者：Masatoshi Kiuchi、Kunitomo Adachi、Ayumi Tomatsu、Masao Chino、Shuzo Takeda、Yoshihito Tanaka、Yasuhiro Maeda、Noriko Sato、Naoko Mitsutomi、Kunio Sugahara、Kenji Chiba

  DOI：10.1016/j.bmc.2004.10.008

  日期：2005.1

  A practical asymmetric synthesis of both enantiomers of the immunosuppressive FTY720-phosphate (2) was accomplished, and the enantiomers were pharmacologically evaluated. Several lipases showed considerable activity and enantioselectivity for O-acylation of N-acetyl FTY720 (3) or N-benzyloxycarbonyl FTY720 (7) in combination with vinyl acetate or benzyl vinyl carbonate as the acyl donors. The synthesis

  完成了对免疫抑制性FTY720-磷酸酯（2）的两种对映异构体的实际不对称合成，并通过药理学评估了该对映异构体。几种脂肪酶与N-乙酰基FTY720（3）或N-苄氧基羰基FTY720（7）结合乙酸乙烯酯或碳酸苄基乙烯基酯作为酰基供体，对O-酰化显示出显着的活性和对映选择性。使用脂肪酶催化的酰化作用作为关键步骤的合成产生了对映体纯的（> 99.5％ee）对映体，数量为2克。（2）的（S）-异构体比（R）-2具有更强的与S1P（1,3,4,5）的结合亲和力和对淋巴细胞向S1P迁移的抑制活性，这表明2的（S）-异构体对给药1后的免疫抑制活性。
• [EN] PHOSPHATE DERIVATIVES AS IMMUNOREGULATORY AGENTS<br/>[FR] DERIVES DE PHOSPHATES UTILISES EN TANT QU'AGENTS IMMUNO-REGULATEURS
  申请人：MERCK & CO INC

  公开号：WO2002018395A1

  公开（公告）日：2002-03-07

  Immunoregulatory compounds are disclosed of the formula: and as well as the pharmaceutically acceptable salts and hydrates thereof, are disclosed. The compounds are useful for treating immune mediated diseases and conditions, such as bone marrow, organ and tissue transplant rejection. Pharmaceutical compositions and methods of use are included.

  公开了如下式的免疫调节化合物：以及其药学上可接受的盐和水合物。该化合物可用于治疗免疫介导的疾病和病况，如骨髓、器官和组织移植排斥反应。还包括制药组合物和使用方法。
• FTY720 HALOGENATED DERIVATIVES
  申请人：Auberson Yves

  公开号：US20120244071A1

  公开（公告）日：2012-09-27

  There are provided new iodo- and bromo-compounds, and their use as diagnostic agents and imaging agents for diseases and disorders wherein S1P receptor expression is altered.

  提供了新的碘和溴化合物，并将其用作诊断剂和成像剂，用于表达S1P受体发生改变的疾病和疾病的诊断和成像。