(S)-2-氨基-3-(苯并呋喃-3-基)丙酸 | 72120-70-8

• 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
• 中文名称: (S)-2-氨基-3-(苯并呋喃-3-基)丙酸
• 中文别名: 3-(3-苯并呋喃基)-L-丙氨酸
• 英文名称: L-benzofuran-3-yl-alanine
• 英文别名: L-2-amino-3-benzofuran-3-yl-propionic acid；L-2-amino-3-(benzofuran-3-yl)propanoic acid；(S)-2-amino-3-(benzofuran-3-yl)propanoic acid；β-(3-benzofuranyl)-(D,L)-alanine；(2S)-2-azaniumyl-3-(1-benzofuran-3-yl)propanoate
• CAS: 72120-70-8
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: IIQKYWMOMQWBER-VIFPVBQESA-N

物化性质

• 沸点：
  373.1±32.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  76.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-氨基-3-(苯并呋喃-3-基)丙酸 在 lithium aluminium tetrahydride 、 三聚氯氰 、 硫酸 、 水 、 silver nitrate 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 42.0h， 生成 [(1R,2R,3R,3'S,11S,12S,14R,26R)-5,12-dihydroxy-3'-(hydroxymethyl)-6-methoxy-7,21,30-trimethyl-27-oxospiro[17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.13,11.02,13.04,9.015,23.016,20]triaconta-4(9),5,7,15,20,22-hexaene-26,1'-3,4-dihydro-2H-[1]benzofuro[2,3-c]pyridine]-22-yl] acetate
  参考文献：
  名称：

  WO2020084115A5

  摘要：

  公开号：

  WO2020084115A5
• 作为产物：
  描述：

  4-(benzofuran-3-ylmethyl)-2-methyloxazol-5(4H)-one 在 丙醇 、 Candida antarctica B lipase 、 sodium carbonate 、 lithium hydroxide 、 Acylase I 、 cobalt(II) chloride 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 生成 (S)-2-氨基-3-(苯并呋喃-3-基)丙酸 、 D-2-acetamido-3-(benzofuran-3-yl)propanoic acid
  参考文献：
  名称：

  Chemoenzymatic preparation of enantiopure l-benzofuranyl- and l-benzo[b]thiophenyl alanines

  摘要：

  Lipase mediated DKR followed by a chemical and an enzymatic hydrolytic step were combined for the synthesis of enantiopure L-benzofuranyl- and L-benzothienyl alanines. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2008.01.031

文献信息

• The Interaction of Heteroaryl-Acrylates and Alanines with Phenylalanine Ammonia-Lyase from Parsley
  作者：Csaba Paizs、Adrian Katona、János Rétey

  DOI：10.1002/chem.200501034

  日期：2006.3.20

  Acrylic acids and alanines substituted with heteroaryl groups at the beta-position were synthesized and spectroscopically characterized (UV, HRMS, (1)H NMR, and (13)C NMR spectroscopy). The heteroaryl groups were furanyl, thiophenyl, benzofuranyl, and benzothiophenyl and contained the alanyl side chains either at the 2- or 3-positions. While the former are good substrates for phenylalanine ammonia-lyase

  合成了在β位置被杂芳基取代的丙烯酸和丙氨酸，并进行了光谱表征（UV，HRMS，（1）H NMR和（13）C NMR光谱）。杂芳基基团是呋喃基，噻吩基，苯并呋喃基和苯并噻吩基，并且在2-或3-位含有丙酰基侧链。前者是苯丙氨酸解氨酶（PAL）的良好底物，而后者是抑制剂。例外的是噻吩-3-基丙氨酸（一种中等的底物）和呋喃-3-基丙氨酸（惰性）。讨论了这些例外的可能原因。从外消旋杂芳基-2-丙氨酸开始，它们的D-对映异构体通过立体破坏方法制备。由杂芳基-2-丙烯酸酯以高氨浓度制备杂芳基-2-丙氨酸的L-对映异构体。
• IDO Inhibitors
  申请人：Mautino Mario

  公开号：US20110053941A1

  公开（公告）日：2011-03-03

  Presently provided are methods for (a) modulating an activity of indoleamine 2,3-dioxygenase comprising contacting an indoleamine 2,3-dioxygenase with a modulation effective amount of a compound as described in one of the aspects described herein; (b) treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression in a subject in need thereof, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (c) treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (d) enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent and a compound as described in one of the aspects described herein; (e) treating tumor-specific immunosuppression associated with cancer comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; and (f) treating immunosuppression associated with an infectious disease, e.g., HIV-I infection, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount a compound as described in one of the aspects described herein.

  目前提供以下方法：(a) 通过接触本文中描述的化合物的调节有效量与吲哚胺2,3-二氧化酶相互作用，从而调节吲哚胺2,3-二氧化酶的活性；(b) 治疗需要吲哚胺2,3-二氧化酶(IDO)介导的免疫抑制的患者，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(c) 治疗需要抑制吲哚胺-2,3-二氧化酶酶活性的医疗状况，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(d) 增强抗癌治疗的有效性，包括给予抗癌剂和本文中描述的化合物；(e) 治疗与癌症相关的肿瘤特异性免疫抑制，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(f) 治疗与传染病相关的免疫抑制，例如HIV-1感染，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量。
• Antigen-presenting cell populations and their use as reagents for enhancing or reducing immune tolerance
  申请人：Medical College of Georgia Research Institute, Inc

  公开号：EP2177601A1

  公开（公告）日：2010-04-21

  The present invention is based on the discovery antigen-presenting cells (APCs) may be generated to have predetermined levels of expression of the intracellular enzyme, indoleamine 2,3-dioxygenase (IDO). Because expression of high levels of IDO is correlated with a reduced ability to stimulate T cell responses and an enhanced ability to induce immunologic tolerance, APCs having high levels of IDO may be used to increase tolerance in the immune system, as for example in transplant therapy or treatment of autoimmune disorders. For example, APCs having high levels of IDO, and expressing or loaded with at least one antigen from a donor tissue may be used to increase tolerance of the recipient to the donor's tissue. Alternatively, APCs having reduced levels of IDO expression and expressing or loaded with at least one antigen from a cancer or infectious pathogen may be used as vaccines to promote T cell responses and increase immunity.

  本发明的基础是发现抗原递呈细胞（APCs）可以生成具有预定表达水平的细胞内酶--吲哚胺 2,3-二氧化酶（IDO）。由于高水平 IDO 的表达与刺激 T 细胞反应的能力降低和诱导免疫耐受的能力增强相关，因此具有高水平 IDO 的 APCs 可用来增加免疫系统的耐受性，例如在移植疗法或自身免疫性疾病的治疗中。例如，具有高水平 IDO 并表达或负载至少一种供体组织抗原的 APCs 可用于提高受体对供体组织的耐受性。另外，IDO 表达水平降低、表达或负载至少一种癌症或传染性病原体抗原的 APCs 可用作疫苗，以促进 T 细胞反应并增强免疫力。
• CD28H STIMULATION ENHANCES NK CELL KILLING ACTIVITIES
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3800201A1

  公开（公告）日：2021-04-07

  CD28H (TMIGD2 or IGPR-1) belongs to the CD28 family and is a transmembrane protein with an immunoglobulin-like extracellular domain, a transmembrane domain and a cytoplasmic tail. The main objective of the inventors was to evaluate the consequences of CD28H stimulation on NK with a monoclonal anti-CD28H antibody (clone 4-5) known to activate T cells. The inventors show that circulating CD56bright and CD56dim NK cells express the same level of CD28H. Circulating CD28H+ NK cells are more activated than CD28Hneg, in fact NK CD28H+ cells express more CD69, NKp30 and Nkp46. The agonist anti-CD28H mAb induces a calcium flux in NK cells while the blocking mAb does not. Calcium flux evaluation shows that CD28H synergize with NKP46 but not with CD16. After an overnight stimulation with the agonist anti-CD28H mAb, NK cells express more CD69, Nkp30, NKG2D and less CD16 compared to a control condition with an isotype mAb. This reflects a very strong activation of NK cells. Moreover, the CD28H-primed NK cells treated with the agonistic anti-CD28H mAb secret more granzyme B and more IFN-g in presence of K562. CD28H-primed NK cells increase their cytotoxic capacities against tumor cell lines. When used in vivo in a xeno-GVHD model in NSG-SGM3 mice, the agonistic anti-CD28H mAb increases the frequency of NK cells suggesting a potential role of CD28H in NK homeostasis. Thus CD28H is a strong activator of NK cells and is the potential new therapeutic target for cancer immunotherapy

  CD28H（TMIGD2 或 IGPR-1）属于 CD28 家族，是一种跨膜蛋白，具有免疫球蛋白样胞外结构域、跨膜结构域和胞质尾部。发明者的主要目的是评估 CD28H 刺激 NK 与已知能激活 T 细胞的单克隆抗 CD28H 抗体（克隆 4-5）的后果。发明人发现，循环中 CD56bright 和 CD56dim NK 细胞表达相同水平的 CD28H。循环中的 CD28H+ NK 细胞比 CD28Hneg 更活化，事实上，NK CD28H+ 细胞表达更多的 CD69、NKp30 和 Nkp46。激动剂抗 CD28H mAb 能诱导 NK 细胞中的钙通量，而阻断 mAb 则不能。钙通量评估显示，CD28H 与 NKP46 有协同作用，但与 CD16 没有协同作用。与使用同种型 mAb 的对照组相比，在使用激动剂抗 CD28H mAb 刺激过夜后，NK 细胞表达更多的 CD69、Nkp30 和 NKG2D，而表达更少的 CD16。这反映出 NK 细胞被强烈激活。此外，在有 K562 存在的情况下，用激动抗 CD28H mAb 处理的 CD28H 催化 NK 细胞会分泌更多的颗粒酶 B 和更多的 IFN-g。CD28H刺激的NK细胞提高了对肿瘤细胞株的细胞毒能力。在NSG-SGM3小鼠体内的异种-GVHD模型中，激动抗CD28H mAb可增加NK细胞的频率，这表明CD28H在NK平衡中的潜在作用。因此，CD28H 是 NK 细胞的强激活剂，是癌症免疫疗法的潜在新治疗靶点。
• Antitumoral compounds
  申请人：Pharma Mar, S.A.

  公开号：US10538535B2

  公开（公告）日：2020-01-21

  A compound of general formula I, wherein X, R1-R4 take various meanings, for use in the treatment of cancer.

  一种通式 I 的化合物，其中 X、R1-R4 具有各种含义，用于治疗癌症。