methyl (2S)-2-amino-3-(3,4-difluorophenyl)propanoate hydrochloride

• 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: methyl (2S)-2-amino-3-(3,4-difluorophenyl)propanoate hydrochloride
• 英文别名: Methyl (S)-2-amino-3-(3,4-difluorophenyl)propanoate hydrochloride；methyl (2S)-2-amino-3-(3,4-difluorophenyl)propanoate;hydrochloride
• 化学式: C₁₀H₁₁F₂NO₂*ClH
• 分子量: 251.661
• InChiKey: LJHGOOQIEAHDNC-FVGYRXGTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.43
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-amino-3-(3,4-difluorophenyl)propanoate hydrochloride 在 lithium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 (S)-2-{[(S)-1-(3,5-Dichloro-benzenesulfonyl)-pyrrolidine-2-carbonyl]-amino}-3-(3,4-difluoro-phenyl)-propionic acid
  参考文献：
  名称：

  Substituted N-(3,5-Dichlorobenzenesulfonyl)-l-prolyl-phenylalanine analogues as potent VLA-4 antagonists

  摘要：

  A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha-methyl-L-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50 similar to I nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00821-6
• 作为产物：
  描述：

  BOC-L-3,4-二氟苯丙氨酸 在 盐酸 、 氯化亚砜 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 22.0h， 生成 methyl (2S)-2-amino-3-(3,4-difluorophenyl)propanoate hydrochloride
  参考文献：
  名称：

  [EN] ENZYME INHIBITORS
  [FR] INHIBITEURS D'ENZYMES

  摘要：

  本发明提供了如下式(I)的化合物：化合物组合物；在治疗中使用这些化合物；以及使用这些化合物治疗患者的方法；其中A、Y、n、R1、R2A、R2B、R3和*1如本文所定义。

  公开号：

  WO2021032933A1

文献信息

• HETEROCYCLIC COMPOUNDS USEFUL IN THE TREATMENT OF DISEASE
  申请人：EPIGEN BIOSCIENCES, INC.

  公开号：US20160024031A1

  公开（公告）日：2016-01-28

  Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and inflammatory bowel disease; ocular diseases such as diseases involving retinal degeneration; nerve diseases such as pruritus and pain. Non-limiting examples of those compounds include (RS)-3-Cyclopropyl-2-4-[3-methyl-4((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}-propionic acid and (R)-1-(4′-5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-4-fluoro-pyrazol-1-yl}-2-fluoro-biphenyl-4-yl)-cyclopropanecarboxylic acid.

  描述了异环化合物，这些化合物是溶血磷脂酸受体配体，可用于治疗溶血磷脂酸受体依赖性疾病和状况，包括但不限于涉及纤维化的疾病，如心脏、肾脏、肝脏和肺的纤维化以及硬化病；炎症性疾病，如糖尿病肾病和炎症性肠病；眼病，如涉及视网膜变性的疾病；神经疾病，如瘙痒和疼痛。这些化合物的非限制性例子包括(RS)-3-环丙基-2-4-[3-甲基-4((R)-1-苯基-乙氧羰基氨基)-异恶唑-5-基]-苄氧基}-丙酸和(R)-1-(4′-5-[1-(2-氯-苯基)-乙氧羰基氨基]-4-氟-吡唑-1-基}-2-氟-联苯-4-基)-环丙烷甲酸。
• Synthesis of Clovamide Analogues That Inhibit NO Production in Activated BV-2 Microglial Cells
  作者：Ju-Young Park、Byung-Wook Kim、Hae Un Lee、Dong-Kug Choi、Sung-Hwa Yoon

  DOI：10.1248/bpb.b17-00303

  日期：——

  A series of methyl ester of clovamide analogues, where the hydroxyl group of catechol moiety in caffeic acid and L-3,4-dihydroxyphenylalanine (L-dopa) was replaced with various functional groups, were synthesized and their inhibitory effects on nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells were tested. Among the synthesized compounds, 3,5-ditrifluoromethyl analogue 9l (IC50=2.8 µM) exhibited a potency about 26.3 times greater than that of the parent compound 9a (IC50=73.6 µM) and suppressed NO production dose-dependently without cytotoxicity. Compound 9l also inhibited iNOS expression in LPS-induced BV2 cells at 2.5, 5 and 10 µM concentrations. These results suggested that the dihydroxyl group of catechol moiety in caffeic acid unit is not essential for the suppression of NO production and that 9l has potential as a potent inhibitor of NO production.

  研究人员合成了一系列氯伐酰胺甲酯类似物，用不同的官能团取代了咖啡酸和 L-3,4-二羟基苯丙氨酸（L-多巴）中儿茶酚分子的羟基，并测试了它们对脂多糖（LPS）诱导的 BV2 细胞中一氧化氮（NO）产生和诱导型 NO 合酶（iNOS）表达的抑制作用。在合成的化合物中，3,5-二三氟甲基类似物 9l（IC50=2.8 µM）的效力约为母体化合物 9a（IC50=73.6 µM）的 26.3 倍，并能剂量依赖性地抑制一氧化氮的产生，且无细胞毒性。在 2.5、5 和 10 µM 浓度下，化合物 9l 还能抑制 LPS 诱导的 BV2 细胞中 iNOS 的表达。这些结果表明，咖啡酸单位中儿茶酚分子的二羟基对于抑制 NO 的产生并不是必不可少的，9l 有潜力成为一种有效的 NO 生成抑制剂。
• Heterocyclic compounds useful in the treatment of disease
  申请人：EPIGEN BIOSCIENCES, INC.

  公开号：US10000459B2

  公开（公告）日：2018-06-19

  Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and inflammatory bowel disease; ocular diseases such as diseases involving retinal degeneration; nerve diseases such as pruritus and pain. Non-limiting examples of those compounds include (RS)-3-Cyclopropyl-2-4-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}-propionic acid and (R)-1-(4′-5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-4-fluoro-pyrazol-1-yl}-2-fluoro-biphenyl-4-yl)-cyclopropanecarboxylic acid.

  所述杂环化合物是溶血磷脂酸受体配体，可用于治疗溶血磷脂酸受体依赖性疾病和病症，包括但不限于涉及纤维化的疾病，如心脏、肾脏、肝脏和肺部纤维化以及硬皮病；炎症性疾病，如糖尿病肾病和炎症性肠病；眼部疾病，如涉及视网膜变性的疾病；神经疾病，如瘙痒和疼痛。这些化合物的非限制性实例包括 (RS)-3-Cyclopropyl-2-4-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}- 丙酸和 (R)-3-Cyclopropyl-2-4-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}- 丙酸。丙酸和(R)-1-(4′-5-[1-(2-氯苯基)-乙氧羰基氨基]-4-氟吡唑-1-基}-2-氟联苯-4-基)-环丙烷羧酸。
• ENZYME INHIBITORS
  申请人：Kalvista Pharmaceuticals Limited

  公开号：EP4017586A1

  公开（公告）日：2022-06-29
• Heterocyclic Compounds Useful In The Treatment of Disease
  申请人：EPIGEN BIOSCIENCES, INC.

  公开号：US20180297962A1

  公开（公告）日：2018-10-18

  Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and nonalcoholic steatohepatitis (NASH); ocular diseases such as diseases involving retinal degeneration; nerve diseases such as pruritus and pain.