(RS)-2,2,4-trimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester | 185525-61-5

• 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: (RS)-2,2,4-trimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester
• 英文别名: 3-(tert-butoxycarbonyl)-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid；2,2-dimethyl-3-(t-butyloxycarbonyl)-4-methyl-oxazolidine-4-carboxylic acid；2,2,4-trimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester；3-(tert-Butoxycarbonyl)-2,2,4-trimethyloxazolidine-4-carboxylic acid；2,2,4-trimethyl-3-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-oxazolidine-4-carboxylic acid
• CAS: 185525-61-5
• 化学式: C₁₂H₂₁NO₅
• 分子量: 259.302
• InChiKey: OKNXSCGZVJNPQA-UHFFFAOYSA-N

物化性质

• 沸点：
  359.7±42.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (RS)-2,2,4-trimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 在 乙酸铵 、 caesium carbonate 作用下， 以 乙醇 、 xylene 为溶剂， 反应 8.0h， 生成 2,2,4-trimethyl-4-[5-(4-octyl-phenyl)-1H-imidazol-2-yl]-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of 4(5)-phenylimidazole-based analogues of sphingosine-1-phosphate and FTY720: Discovery of potent S1P1 receptor agonists

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2005.05.097
• 作为产物：
  描述：

  methyl 2-((tert-butoxycarbonyl)amino)-3-hydroxy-2-methylpropanoate 在 三氟化硼乙醚 lithium hydroxide 、 水 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 10.0h， 生成 (RS)-2,2,4-trimethyl-oxazolidine-3,4-dicarboxylic acid 3-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

• [EN] METHODS AND COMPOSITIONS FOR MODULATING SPHINGOSINE-1-PHOSPHATE (S1P) RECEPTOR ACTIVITY<br/>[FR] PROCEDES ET COMPOSITIONS SERVANT A MODULER L'ACTIVITE DU RECEPTEUR DE LA SPHINGOSINE-1-PHOSPHATE (S1P)
  申请人：PRAECIS PHARM INC

  公开号：WO2006020951A1

  公开（公告）日：2006-02-23

  The present invention relates to compounds which modulate the activity of the SI P1 receptor, the use of these compounds for treating conditions associated with signaling through the S1 P1 receptor, and pharmaceutical compositions comprising these compounds.

  本发明涉及调节SI P1受体活性的化合物，以及利用这些化合物治疗与S1 P1受体信号传导相关的疾病的用途，以及包含这些化合物的药物组合物。
• Synthesis and biological evaluation of sphingosine kinase substrates as sphingosine-1-phosphate receptor prodrugs
  作者：Frank W. Foss、Thomas P. Mathews、Yugesh Kharel、Perry C. Kennedy、Ashley H. Snyder、Michael D. Davis、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1016/j.bmc.2009.04.015

  日期：2009.8

  sphingosine 1-phosphate (S1P) receptor ligands, a series of 2-amino-2-heterocyclic-propanols were synthesized. These molecules were discovered to be substrates of human-sphingosine kinases 1 and 2 (SPHK1 and SPHK2). When phosphorylated, the resultant phosphates showed varied activities at the five sphingosine-1-phosphate (S1P) receptors (S1P1–5). Agonism at S1P1 was displayed in vivo by induction of lymphopenia

  在寻找生物活性鞘氨醇 1-磷酸 (S1P) 受体配体的过程中，合成了一系列 2-氨基-2-杂环丙醇。这些分子被发现是人鞘氨醇激酶 1 和 2（SPHK1 和 SPHK2）的底物。磷酸化后，生成的磷酸盐对五种 1-磷酸鞘氨醇 (S1P) 受体 (S1P 1–5 )显示出不同的活性。S1P 1 的激动通过诱导淋巴细胞减少在体内显示。季碳的立体化学偏好对于激酶的磷酸化和改变 S1P 受体的结合亲和力至关重要。恶唑和恶二唑化合物是优于 FTY720（原型前药免疫调节剂芬戈莫德 (FTY720)）的激酶底物。恶唑衍生的结构对人 SPHK2 的活性最强。咪唑类似物是 SPHK 活性较低的底物，但对 S1P 1受体而言是更有效和选择性的激动剂；此外，咪唑类化合物使小鼠淋巴细胞减少。
• IMIDAZOPYRIDINE COMPOUNDS
  申请人：Astellas Pharma Inc.

  公开号：US20150232464A1

  公开（公告）日：2015-08-20

  [Problem] A pharmaceutical composition for treating or preventing various cardiovascular diseases, which have sGC activities based on improvement of cGMP signals, is provided. [Means for Solution] It was found that imidazo[1,2-a]pyridine compounds having a carbamoyl group at the 3-position and a particular cyclic group at the 8-position via a methyleneoxy group, or a salt thereof have sGC activation, and are useful as active ingredients of pharmaceutical compositions for treating or preventing various sGC-related cardiovascular diseases, in particular, peripheral arterial diseases, intermittent claudication, critical limb ischemia, hypertension, and pulmonary hypertension, thereby completing the present invention.

  提供一种用于治疗或预防各种心血管疾病的药物组合物，该组合物基于改善cGMP信号的sGC活性。发现在3-位置具有羰胺基团和通过亚甲氧基团在8-位置具有特定环状基团的咪唑并[1,2-a]吡啶化合物或其盐具有sGC激活作用，并且可用作治疗或预防各种sGC相关心血管疾病的药物组合物的活性成分，特别是外周动脉疾病、间歇性跛行、危重肢体缺血、高血压和肺动脉高压，从而完成了本发明。
• Methods and compositions for modulating sphingosine-1-phosphate (S1P) receptor activity
  申请人：Saha K. Ashis

  公开号：US20060135786A1

  公开（公告）日：2006-06-22

  The present invention relates to compounds which modulate the activity of the S1P1 receptor, the use of these compounds for treating conditions associated with signaling through the S1P1 receptor, and pharmaceutical compositions comprising these compounds.

  本发明涉及调节S1P1受体活性的化合物，使用这些化合物治疗与S1P1受体信号传导相关的疾病，并包括这些化合物的药物组合物。
• 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。