(4S)-3-(tert-butoxycarbonyl)-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid | 876915-46-7

• 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: (4S)-3-(tert-butoxycarbonyl)-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid
• 英文别名: (S)-3-tert-butoxycarbonyl-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid；(S)-2,2,4-trimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester；(S)-3-(tert-butoxycarbonyl)-2,2,4-trimethyloxazolidine-4-carboxylic acid；(4S)-3-{[(1,1-dimethylethyl)oxy]carbonyl}-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid；3-(1,1-dimethylethyl)-4-methyl-(S)-2,2-dimethyl-3,4-oxazolidinedi-carboxylate；(4S)-2,2,4-trimethyl-3-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-oxazolidine-4-carboxylic acid
• CAS: 876915-46-7
• 化学式: C₁₂H₂₁NO₅
• 分子量: 259.302
• InChiKey: OKNXSCGZVJNPQA-LBPRGKRZSA-N

物化性质

• 熔点：
  124 °C
• 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：

  (4S)-3-(tert-butoxycarbonyl)-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid 在 盐酸羟胺 、 sodium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-tert-butyl 2,2,4-trimethyl-4-(3-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)oxazolidine-3-carboxylate
  参考文献：
  名称：

  WO2008/16692

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-2-N-(tert-butoxycarbonyl)amino-2-methyl-3-hydroxypropanoic acid methyl ester 在 硫酸 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.5h， 生成 (4S)-3-(tert-butoxycarbonyl)-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid
  参考文献：
  名称：

  Complementary Syntheses of N,O-Protected-(S)-2-methylserine on a Multikilogram Scale

  摘要：

  Two complementary and scalable approaches have been used to manufacture multikilogram quantities of N,O-protected-(S)-2-methylserine. The first approach uses a diastereomeric salt resolution of 2-methylserine methyl ester as the (1S)-(+)-camphorsulfonate salt, and was used to rapidly access 15 kg of (S)-3-tert-butoxycarbonyl-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid with > 99% ee. The second approach involves a stereoselective enolate methylation of a chiral cyclic L-serine derivative under cryogenic conditions. The four-step telescoped process, starting from L-serine methyl ester, was used to manufacture 20 kg of (2R,4S)-2-tert-butyl-3-tert-butoxycarbonyl-4-methyl-1,3-oxazolidine-4-carboxylic acid in 52% overall yield and 98% ee. The advantages and disadvantages for scale-up of both approaches are discussed.

  DOI：

  10.1021/op100299d

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。
• [EN] THE HEMI-FUMARATE SALT OF A 1,3,4-THIADIAZOLYL DERIVATIVE AS MODULATOR OF THE SPHINGOSINE 1-PHOSPHATE RECEPTOR<br/>[FR] SEL HÉMI-FUMARATE D'UN DÉRIVÉ DE 1,3,4-THIADIAZOLYLE COMME MODULATEUR DU RÉCEPTEUR DE LA SPHINGOSINE 1-PHOSPHATE
  申请人：GLAXO GROUP LTD

  公开号：WO2009098193A1

  公开（公告）日：2009-08-13

  The invention relates to the compound (2S)-2-amino-2-5-[4-(octyloxy)-3- (trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-1-propanol hemi-fumarate, processes for its preparation, pharmaceutical compositions containing them and its use in the treatment of conditions or disorders which are mediated via the S1 P1 receptor.

  该发明涉及化合物（2S）-2-氨基-2-5-[4-(辛氧基)-3-（三氟甲基）苯基]-1,3,4-噻二唑-2-基}-1-丙醇半富马酸盐，其制备方法，含有该化合物的药物组合物以及其在通过S1 P1受体介导的病症或紊乱的治疗中的用途。
• 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。