3-(p-fluorobenzylthio) alanine | 40379-67-7

• 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: 3-(p-fluorobenzylthio) alanine
• 英文别名: 2(R)-amino-3-(4-fluorobenzylsulfanyl)-propionic acid；(2R)-2-azaniumyl-3-[(4-fluorophenyl)methylsulfanyl]propanoate
• CAS: 40379-67-7
• 化学式: C₁₀H₁₂FNO₂S
• 分子量: 229.275
• InChiKey: NZOOJAXDPAMBHS-VIFPVBQESA-N

物化性质

• 沸点：
  384.4±42.0 °C(Predicted)
• 密度：
  1.332±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(p-fluorobenzylthio) alanine 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 2(R)-amino-3-(4-fluorobenzylsulfanyl)-propan-1-ol
  参考文献：
  名称：

  [EN] HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
  [FR] COMPOSES CONTENANT UN HALOALKYLE UTILISE COMME INHIBITEURS DE CYSTEINE PROTEASE

  摘要：

  公开号：

  WO2005028429A3
• 作为产物：
  描述：

  L-半胱氨酸盐酸盐无水物 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 生成 3-(p-fluorobenzylthio) alanine
  参考文献：
  名称：

  N-巯基半胱氨酸衍生物作为白三烯A 4水解酶抑制剂的合成及生物学评价

  摘要：

  我们研究了N-巯基酰基氨基酸衍生物的合成修饰，以开发一类新的白三烯A 4（LTA 4）水解酶抑制剂。小号- （4-二甲基氨基）苄基-升-半胱氨酸衍生物2A（SA6541）显示针对LTA抑制活性4水解酶（IC 50，270 nm）的和选择性优于其它金属肽除了血管紧张素转换酶（ACE，IC 50，520 nm）的。化合物2a苯环的对位取代基上的修饰改进了LTA 4水解酶抑制活性以及对ACE的选择性。最后，我们获得了作为有效的和选择性的LTA 4水解酶抑制剂的S-（4-环己基）苯并-1-半胱氨酸衍生物11l和16i。

  DOI：

  10.1016/j.bmcl.2008.11.042

文献信息

• The Protective Effects of Hydrogen Sulfide New Donor Methyl S-(4-Fluorobenzyl)-N-(3,4,5-Trimethoxybenzoyl)-l-Cysteinate on the Ischemic Stroke
  作者：Jing Fan、Junxi Du、Zhongwei Zhang、Wenjing Shi、Binyan Hu、Jiaqin Hu、Yan Xue、Haipeng Li、Wenjin Ji、Jian Zhuang、Pengcheng Lv、Kui Cheng、Kun Chen

  DOI：10.3390/molecules27051554

  日期：——

  In this paper, we report the design, synthesis and biological evaluation of a novel S-allyl-l-cysteine (SAC) and gallic acid conjugate S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-l-cysteinate (MTC). We evaluate the effects on ischemia-reperfusion-induced PC12 cells, primary neurons in neonatal rats, and cerebral ischemic neuronal damage in rats, and the results showed that MTC increased SOD, CAT, GPx activity and decreased LDH release. PI3K and p-AKT protein levels were significantly increased by activating PI3K/AKT pathway. Mitochondrial pro-apoptotic proteins Bax and Bim levels were reduced while anti-apoptotic protein Bcl-2 levels were increased. The levels of cleaved caspase-9 and cleaved caspase-3 were also reduced in the plasma. The endoplasmic reticulum stress (ERS) was decreased, which in turns the survival rate of nerve cells was increased, so that the ischemic injury of neurons was protected accordingly. MTC activated the MEK-ERK signaling pathway and promoted axonal regeneration in primary neurons of the neonatal rat. The pretreatment of MEK-ERK pathway inhibitor PD98059 and PI3K/AKT pathway inhibitor LY294002 partially attenuated the protective effect of MTC. Using a MCAO rat model indicated that MTC could reduce cerebral ischemia-reperfusion injury and decrease the expression of proinflammatory factors. The neuroprotective effect of MTC may be due to inhibition of the over-activation of the TREK-1 channel and reduction of the current density of the TREK1 channel. These results suggested that MTC has a protective effect on neuronal injury induced by ischemia reperfusion, so it may have the potential to become a new type of neuro-ischemic drug candidate.

  在本文中，我们报告了一种新型S-烯丙基-L-半胱氨酸（SAC）和没食子酸结合物S-(4-氟苯甲基)-N-(3,4,5-三甲氧基苯甲酰)-L-半胱氨酸酯（MTC）的设计、合成和生物评价。我们评估了MTC对缺血再灌注诱导的PC12细胞、新生大鼠原代神经元和大鼠脑缺血神经损伤的影响，结果表明MTC增加了SOD、CAT、GPx活性并降低LDH释放。通过激活PI3K/AKT通路，PI3K和p-AKT蛋白水平显著增加。线粒体原始凋亡蛋白Bax和Bim水平降低，而抗凋亡蛋白Bcl-2水平增加。血浆中剪切的caspase-9和caspase-3水平也降低了。内质网应激（ERS）减少，从而神经细胞的存活率增加，因此保护了神经元的缺血损伤。MTC激活了MEK-ERK信号通路，并促进了新生大鼠原代神经元的轴突再生。MEK-ERK通路抑制剂PD98059和PI3K/AKT通路抑制剂LY294002的预处理部分减弱了MTC的保护作用。使用MCAO大鼠模型表明，MTC可以减少脑缺血再灌注损伤并降低前炎症因子的表达。MTC的神经保护作用可能是由于抑制了TREK-1通道的过度激活并降低了TREK1通道的电流密度。这些结果表明，MTC对缺血再灌注诱导的神经损伤具有保护作用，因此可能成为一种新型的神经缺血药物候选物。
• Haloalkyl containing compounds as cysteine protease inhibitors
  申请人：Link O. John

  公开号：US20050182096A1

  公开（公告）日：2005-08-18

  The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

  本发明涉及抑制半胱氨酸蛋白酶的化合物，特别是cathepsins B、K、L、F和S，因此可用于治疗由这些蛋白酶介导的疾病。本发明涉及包含这些化合物的药物组合物和制备它们的过程。
• Structure-activity relationship study and biological evaluation of SAC-Garlic acid conjugates as novel anti-inflammatory agents
  作者：Jingjie Bi、Wenqing Wang、Junxi Du、Kun Chen、Kui Cheng

  DOI：10.1016/j.ejmech.2019.06.059

  日期：2019.10

  A series of S-allyl-L-cysteine (SAC) with garlic acid conjugates as anti-inflammatory agents were designed and synthesized. Among the 40 tested compounds, SMU-8c exhibited the most potent inhibitory activity to Pam(3)CSK(4)-induced nitric oxide (NO) in RAW264.7 macrophages with IC50 of 22.54 +/- 2.60 mu M. The structure-activity relationship (SAR) study suggested that the esterified carboxyl group, carbon chain extension and methoxylation phenol hydroxy could improve the anti-inflammatory efficacy. Preliminary anti-inflammatory mechanism studies showed that SMU-8c significantly down-regulated the levels of Pam(3)CSK(4) triggered TNF-alpha cytokine in human THP-1 cells, mouse RAW 264.7 macrophages, as well as in ex-vivo human peripheral blood mononuclear cells (PBMC) with no influence on cell viability. SMU-8c specifically blocked the Pam(3)CSK(4) ignited secreted embryonic alkaline phosphatase (SEAP) signaling with no influence to Poly I:C or LPS triggered TLR3 or TLR4 signaling. Moreover, SMU-8c suppressed TLR2 in HEK-Blue hTLR2 cells and inhibited the formation of TLR1-TLR2, and TLR2-TLR6 complex in human PBMC. In summary, SMU-8c inhibited the TLR2 signaling pathway to down-regulate the inflammation cytokines, such as NO, SEAP and TNF-alpha, to realize its anti-inflammatory activity. (C) 2019 Elsevier Masson SAS. All rights reserved.
• NOVEL SULFUR-CONTAINING AMINO ACID DERIVATIVES
  申请人：SANTEN PHARMACEUTICAL CO., LTD.

  公开号：EP0947502B1

  公开（公告）日：2006-06-21
• HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
  申请人：AXYS PHARMACEUTICALS, INC.

  公开号：EP1663958A2

  公开（公告）日：2006-06-07