benzyl (2S)-3-[bis[(2-methylpropan-2-yl)oxy]phosphoryloxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate | 448959-60-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl (2S)-3-[bis[(2-methylpropan-2-yl)oxy]phosphoryloxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 448959-60-2
• 化学式: C₂₃H₃₈NO₈P
• 分子量: 487.53
• InChiKey: OKKUZQPUSJGREI-SFHVURJKSA-N

物化性质

• 沸点：
  561.2±50.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-3-[bis[(2-methylpropan-2-yl)oxy]phosphoryloxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate 在 palladium on activated charcoal benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Synthesis of para-Alkyl aryl amide analogues of sphingosine-1-phosphate: discovery of potent S1P receptor agonists

  摘要：

  Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several potent S1P receptor agonists. For instance, compound 9c displayed an EC50=8.6 nM at the S1P(1) receptor using a [gamma-S-35]GTP binding assay as compared to an EC50=4.5 nM for the endogenous ligand. We also report the effects associated with introduction of a phenyl ring between the 'linker' and 'lipophilic tail' regions of the analogues, for example total loss of activity at S1P(2) and increased agonism at S1P(5). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00812-6
• 作为产物：
  描述：

  N-叔丁氧羰基-L-丝氨酸 在 四氮唑 、 双氧水 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 benzyl (2S)-3-[bis[(2-methylpropan-2-yl)oxy]phosphoryloxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
  参考文献：
  名称：

  Synthesis of para-Alkyl aryl amide analogues of sphingosine-1-phosphate: discovery of potent S1P receptor agonists

  摘要：

  Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several potent S1P receptor agonists. For instance, compound 9c displayed an EC50=8.6 nM at the S1P(1) receptor using a [gamma-S-35]GTP binding assay as compared to an EC50=4.5 nM for the endogenous ligand. We also report the effects associated with introduction of a phenyl ring between the 'linker' and 'lipophilic tail' regions of the analogues, for example total loss of activity at S1P(2) and increased agonism at S1P(5). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00812-6

文献信息

• Compounds Active in Sphingosine 1-Phosphate Signaling
  申请人：Lynch R. Kevin

  公开号：US20070219163A1

  公开（公告）日：2007-09-20

  The present invention relates to S1P analogs that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure: wherein R 11 is C 5 -C 18 alkyl or C 5 -C 18 alkenyl; Q is C 3 -C 6 optionally substituted cycloalkyl, C 3 -C 6 optionally substituted heterocyclic, C 3 -C 6 optionally substituted aryl C 3 -C 6 optionally substituted heteroaryl or —NH(CO)—; R 3 is H, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)OH or (C 1 -C 4 alkyl)NH 2 ; R 23 is H or C 1 -C 4 alkyl, and R 15 is hydroxy, phosphonate, or wherein X and R 12 is O or S; or a pharmaceutically acceptable salt or tautomer thereof.

  本发明涉及具有S1P受体调节剂活性的S1P类似物，以及使用这些化合物治疗与不适当的S1P受体活性相关的疾病。这些化合物具有以下一般结构：其中R11是C5-C18烷基或C5-C18烯基；Q是C3-C6可选取代的环烷基，C3-C6可选取代的杂环基，C3-C6可选取代的芳基，C3-C6可选取代的杂芳基或—NH（CO）—；R3是H，C1-C4烷基，（C1-C4烷基）OH或（C1-C4烷基）NH2；R23是H或C1-C4烷基，R15是羟基，膦酸酯或其中X和R12是O或S；或其药学上可接受的盐或互变异构体。
• Orally available sphingosine 1-phosphate receptor agonists and antagonists
  申请人：Lynch R. Kevin

  公开号：US20070088002A1

  公开（公告）日：2007-04-19

  The present invention relates to S1P analogs that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure (I) wherein R 11 is C 5 -C 18 alkyl or C 5 -C 18 alkenyl; Q is selected from the group consisting of C 3 -C 6 optionally substituted cycloalkyl, C 3 -C 6 optionally substituted heterocyclic, C 3 -C 6 optionally substituted aryl C 3 -C 6 optionally substituted heteroaryl and; R 2 is selected from the group consisting of H, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)OH and (C 1 -C 4 alkyl)NH 2 ; R 23 is H or C 1 -C 4 alkyl, and R 15 is a phosphonate ester or a phosphate ester or a pharmaceutically acceptable salt or tautomer thereof.

  本发明涉及具有S1P受体调节剂活性的S1P类似物，并使用这些化合物治疗与不适当S1P受体活性相关的疾病。这些化合物具有一般结构（I），其中R11为C5-C18烷基或C5-C18烯基；Q选自C3-C6可选取代的环烷基、C3-C6可选取代的杂环、C3-C6可选取代的芳基、C3-C6可选取代的杂芳基；R2选自H、C1-C4烷基、（C1-C4烷基）OH和（C1-C4烷基）NH2；R23为H或C1-C4烷基，R15为磷酸酯或磷酸酯酯或其药学上可接受的盐或互变异构体。
• [EN] ORALLY AVAILABLE SPHINGOSINE 1-PHOSPHATE RECEPTOR AGONISTS AND ANTAGONISTS<br/>[FR] AGONISTES ET ANTAGONISTES DU RECEPTEUR DE LA SPHINGOSINE-1-PHOSPHATE POUVANT ETRE PRIS PAR VOIE ORALE
  申请人：UNIV VIRGINIA

  公开号：WO2005041899A3

  公开（公告）日：2006-11-02
• US7560477B2
  申请人：——

  公开号：US7560477B2

  公开（公告）日：2009-07-14
• US7638637B2
  申请人：——

  公开号：US7638637B2

  公开（公告）日：2009-12-29