L-baikiain methyl ester

• 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: L-baikiain methyl ester
• 英文别名: (S)-methyl 1,2,3,6-tetrahydropyridine-2-carboxylate；methyl (S)-1,2,3,6-tetrahydropyridine-2-carboxylate；Methyl (2S)-1,2,3,6-tetrahydropyridine-2-carboxylate
• 化学式: C₇H₁₁NO₂
• 分子量: 141.17
• InChiKey: VCOPAQWYNHWABP-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  L-baikiain methyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 (S)-4,5-二去氢哌啶甲酸
  参考文献：
  名称：

  一种新的对映体纯构象受限环状氨基酸的闭环复分解介导途径

  摘要：

  钯催化的 N,O-缩醛形成、钌催化的闭环复分解和 N-磺酰亚胺离子介导的 C-C 键形成的组合构成了一种有效且通用的途径，可生成一组对映体纯的 2,6-二取代不饱和哌可酸衍生物。

  DOI：

  10.1039/b001253j
• 作为产物：
  描述：

  (S)-methyl 2-(2-nitrophenylsulfonamido)pent-4-enoate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 双氧水 、 potassium carbonate 、 caesium carbonate 、 苯硫酚 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 14.25h， 生成 L-baikiain methyl ester
  参考文献：
  名称：

  [EN] SELECTIVE FKBP51 LIGANDS FOR TREATMENT OF PSYCHIATRIC DISORDERS
  [FR] LIGANDS SÉLECTIFS DE LA FKBP51 DESTINÉS AU TRAITEMENT DE TROUBLES PSYCHIATRIQUES

  摘要：

  本发明涉及具有选择性FKBP51配体支架的一般式(I)化合物，这些化合物的药学上可接受的盐以及含有至少一种这些化合物的药学上可接受的载体、赋形剂和/或稀释剂的药物组合物。所述选择性FKBP51配体化合物可用于预防和/或治疗精神障碍和神经退行性疾病、障碍和症状。

  公开号：

  WO2015039758A1

文献信息

• Synthesis of a potential “suicide substrate” of the HIV-1 protease, incorporating A 3-acetoxy-Δ-4,5-(L)-pipecolic acid as proline substitute.
  作者：Jean-Paul Mazaleyrat、Isabelle Rage、Juan Xie、Jaroslav Savrda、Michel Wakselman

  DOI：10.1016/s0040-4039(00)60108-9

  日期：1992.7

  a 3S-hydroxy-4S-iodo-(L)-pipecolic acid or a 3R-hydroxy-4R-iodo-(D)-pipecolic acid residue, which were separated by thin layer chromatography. Assignment of configuration was unambiguous when the synthesis was repeated with (L)-baikiain as starting material. All compounds exhibited conformational isomerism in their1H NMR spectra, attributed to the existence of boths-cis ands-trans configurations of

  （D，L）-拜甲氨酸甲酯与Boc-（L）-苯丙氨酸偶联，然后通过（L）-异亮烷基-（L）-缬氨酸甲酯对非对映异构体碘代内酯进行皂化，偶氮内酯化和氨解，得到两个掺入了非对映异构体的肽无论是3 š羟基-4小号-碘（L）-pipecolic酸或3 - [R -羟基-4 - [R -碘（d）-pipecolic酸残基，这是由薄层色谱法分离。当以（L）-baikiain为起始原料重复合成时，构型的分配是明确的。所有化合物在其1 H NMR光谱中均显示出构象异构现象，这归因于同时存在s-顺式和s-反式Phe-NR 2肽键的构型。两个分离的非对映异构体中的每一个的乙酰化得到Boc-（L）-Phe-3 S -OAc-4 S -I-（L）-Pip-（L）-Ile-（L）-Val-OMe和Boc-（ L）-Phe-3 R -OAc-4 R -I-（D）-Pip-（L）-Ile-（L）-Val-OMe。N-脱保护并通过DCC
• [EN] MACROCYCLES AS CFTR MODULATORS<br/>[FR] MACROCYCLES EN TANT QUE MODULATEURS DE CFTR
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：WO2022194399A1

  公开（公告）日：2022-09-22

  The present invention relates to macrocyclic compounds of Formula (I) wherein Ar1, Ar2, R1, R2, R3, R4, and X are as described in the description, their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of Formula (I), and especially to their use as modulators of CFTR.

  本发明涉及公式（I）的大环化合物，其中Ar1，Ar2，R1，R2，R3，R4和X如描述中所述，它们的制备方法，其药学上可接受的盐以及它们作为药物的用途，包括含有一个或多个公式（I）化合物的药物组合物，特别是它们作为CFTR调节剂的用途。
• Selective FKBP51 ligands for treatment of psychiatric disorders
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：US10246413B2

  公开（公告）日：2019-04-02

  The present invention relates to compounds having a selective FKBP51 ligand scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said selective FKBP51 ligand compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions.

  本发明涉及具有选择性 FKBP51 配体支架的化合物、这些化合物的药学上可接受的盐以及含有至少一种这些化合物和药学上可接受的载体、赋形剂和/或稀释剂的药物组合物。所述选择性 FKBP51 配体化合物可用于预防和/或治疗精神疾病和神经退行性疾病、紊乱和病症。
• Amino compounds for treatment of immune and inflammatory disorders
  申请人：Achillion Pharmaceuticals, Inc.

  公开号：US10906887B2

  公开（公告）日：2021-02-02

  Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I″ and I′″ or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.

  提供了由式I、I″和I′″或其药学上可接受的盐或组合物组成的化合物、使用方法和制造补体因子D抑制剂的工艺。本文所述的抑制剂以因子 D 为靶点，抑制或调节补体级联。本文所述的因子 D 抑制剂可减少补体的过度激活。
• Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52
  作者：Ranganath Gopalakrishnan、Christian Kozany、Steffen Gaali、Christoph Kress、Bastiaan Hoogeland、Andreas Bracher、Felix Hausch

  DOI：10.1021/jm201746x

  日期：2012.5.10

  The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography.