{2-(di-tert-butoxy-thiophosphoryloxy)-1-methyl-1-[5-(4-octyl-phenyl)-1H-imidazol-2-yl]-ethyl}-carbamic acid tert-butyl ester | 654067-55-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: {2-(di-tert-butoxy-thiophosphoryloxy)-1-methyl-1-[5-(4-octyl-phenyl)-1H-imidazol-2-yl]-ethyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[1-[bis[(2-methylpropan-2-yl)oxy]phosphinothioyloxy]-2-[5-(4-octylphenyl)-1H-imidazol-2-yl]propan-2-yl]carbamate
• CAS: 654067-55-7
• 化学式: C₃₃H₅₆N₃O₅PS
• 分子量: 637.865
• InChiKey: OXTSITLLZLFQNJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.087±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  43
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  {2-(di-tert-butoxy-thiophosphoryloxy)-1-methyl-1-[5-(4-octyl-phenyl)-1H-imidazol-2-yl]-ethyl}-carbamic acid tert-butyl ester 在 三甲基溴硅烷 、 苯硫酚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以94%的产率得到thiophosphoric acid mono-{2-amino-2-[5-(4-octyl-phenyl)-1H-imidazol-2-yl]-propyl}ester
  参考文献：
  名称：

  [EN] ORALLY AVAILABLE SPHINGOSINE 1-PHOSPHATE RECEPTOR AGONISTS AND ANTAGONISTS
  [FR] AGONISTES ET ANTAGONISTES DU RECEPTEUR DE LA SPHINGOSINE-1-PHOSPHATE POUVANT ETRE PRIS PAR VOIE ORALE

  摘要：

  公开号：

  WO2005041899A3
• 作为产物：
  描述：

  1-苯基辛烷 在 四氮唑 、 aluminum (III) chloride 、 水 、 sodium carbonate 、 caesium carbonate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 49.17h， 生成 {2-(di-tert-butoxy-thiophosphoryloxy)-1-methyl-1-[5-(4-octyl-phenyl)-1H-imidazol-2-yl]-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] ORALLY AVAILABLE SPHINGOSINE 1-PHOSPHATE RECEPTOR AGONISTS AND ANTAGONISTS
  [FR] AGONISTES ET ANTAGONISTES DU RECEPTEUR DE LA SPHINGOSINE-1-PHOSPHATE POUVANT ETRE PRIS PAR VOIE ORALE

  摘要：

  公开号：

  WO2005041899A3

文献信息

• Compounds active in spinigosine 1-phosphate signaling
  申请人：Lynch R. Kevin

  公开号：US20050222422A1

  公开（公告）日：2005-10-06

  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 of Formula (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 —NH(CO)—; 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 selected from the group consisting of hydroxy, phosphonate, and of Formula (II) wherein X and R 15 is selected from the group consisting of O and S; or a pharmaceutically acceptable salt or tautomer thereof.

  本发明涉及具有作为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。这些化合物具有通式（I）的一般结构，其中R11为C5-C18烷基或C5-C18烯基；Q选自C3-C6可选取代环烷基、C3-C6可选取代杂环、C3-C6可选取代芳基、C3-C6可选取代杂芳基和-NH（CO）-的群；R2选自H、C1-C4烷基、（C1-C4烷基）OH和（C1-C4烷基）NH2的群；R23为H或C1-C4烷基，R15选自羟基、膦酸酯和通式（II）的群，其中X和R15选自O和S；或其药学上可接受的盐或互变异构体。
• 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。
• Synthesis of 4(5)-phenylimidazole-based analogues of sphingosine-1-phosphate and FTY720: Discovery of potent S1P1 receptor agonists
  作者：Jeremy J. Clemens、Michael D. Davis、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1016/j.bmcl.2005.05.097

  日期：2005.8

  The novel immunosuppressant FTY720 has been demonstrated to elicit immunomodulating effects via interaction with the G-protein coupled receptor S1P(1). FTY720 induced agonism at the S1P(3) receptor, however, has been shown to result in mild bradycardia, a minor side-effect of initial FTY720 therapy. This report describes the synthesis of several potent 4(5)-phenylimidazole-based SIP, receptor agonists that are accompanied by poor agonist activity at S1P(3). For instance, compound 20 displayed an EC50 = 4.7 +/- 1.3 nM at the S1P(1), receptor and EC50 = 780 +/- 1.3 nM at the SIP3 receptor using a [gamma-S-35]GTP-binding assay as compared to phospho-FTY720 (S1P(1): EC50 = 1.3 +/- 1.3 nM, S1P(3): EC50 = 2.0 +/- 2.4 nM). (c) 2005 Elsevier Ltd. All rights reserved.
• COMPOUNDS ACTIVE IN SPHINGOSINE 1-PHOSPHATE SIGNALING
  申请人：University of Virginia Patent Foundation

  公开号：EP1546110A2

  公开（公告）日：2005-06-29