(S)-tert-butyl 4-(((benzyloxy)carbonyl)amino)-2-hydroxybutanoate | 849773-54-2

• 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: (S)-tert-butyl 4-(((benzyloxy)carbonyl)amino)-2-hydroxybutanoate
• 英文别名: S-Cbz HABA t-butyl ester；tert-butyl (2S)-2-hydroxy-4-(phenylmethoxycarbonylamino)butanoate
• CAS: 849773-54-2
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: XZPOVDLIWZAJSL-ZDUSSCGKSA-N

物化性质

• 沸点：
  465.5±45.0 °C(Predicted)
• 密度：
  1.154±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 4-(((benzyloxy)carbonyl)amino)-2-hydroxybutanoate 在 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.0h， 生成 (R)-4-tert-butoxy-3-(N-isopropoxy-4'-methoxybiphenyl-4-ylsulfonamido)-4-oxobutan-1-aminium acetate
  参考文献：
  名称：

  N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in Vivo Antiangiogenic Activity

  摘要：

  Matrix metalloproteinases (MMPs) have been shown to be involved in tumor-induced angiogenesis. In particular, MMP-2, MMP-9, and MMP-14 have been reported to be crucial for tumor angiogenesis and the formation of metastasis, thus becoming attractive targets in cancer therapy. Here, we report our optimization effort to identify novel N-isopropoxy-arylsulfonamide hydroxamates with improved inhibitory activity toward MMP-2, MMP-9, and MMP-14 with respect to the previously discovered compound 1. A new series of hydroxamates was designed, synthesized, and tested for their antiangiogenic activity using in vitro assays with human umbilical vein endothelial cells (HUVECs). A nanomolar MMP-2, MMP-9, and MMP-14 inhibitor was identified, compound 3, able to potently inhibit angiogenesis in vitro and also in vivo in the matrigel sponge assay in mice. Finally, X-ray crystallographic and docking studies were conducted for compound 3 in order to investigate its binding mode to MMP-9 and MMP-14.

  DOI：

  10.1021/acs.jmedchem.5b00367
• 作为产物：
  描述：

  氯甲酸苄酯 在 sodium carbonate 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 40.0h， 生成 (S)-tert-butyl 4-(((benzyloxy)carbonyl)amino)-2-hydroxybutanoate
  参考文献：
  名称：

  Buchwald-Hartwig 与微波辅助的氯喹啉胺化：通往 Pyoverdin 生色团的途中

  摘要：

  报道了 2-氯-6,7-二甲氧基-3-硝基喹啉与一系列胺和氨基链烷酸酯在碱性微波介导条件和 Buchwald-Hartwig 胺化条件下的反应。微波辐射有利于与胺的反应，产率高达 80%，而氨基酸官能化的产率与 Buchwald-Hartwig 胺化的产率相当。叔丁基 (2R)-4-[(6,7-dimethoxy-3-nitroquinolin-2-yl)amino]-2-hydroxybutanoate 被成功环化为 pyoverdin 生色团，铁载体的一个亚基。

  DOI：

  10.1055/s-0040-1707810

文献信息

• Diagnostic agents selective against metalloproteases
  申请人：Rossello Armando

  公开号：US09480758B2

  公开（公告）日：2016-11-01

  The invention relates to aryl-sulphonamido compounds endowed with affinity against metallo proteases MMP, having formula (I) below wherein R, R1, R2, R3, G and n have the meanings reported in the specification, properly labelled with diagnostic imaging moieties or even radiotherapeutic moieties. The invention also refers to the process for their preparation, to pharmaceutical compositions comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents.

  该发明涉及具有亲和力针对金属蛋白酶MMP的芳基磺胺基化合物，其具有如下式(I)中所示的结构，其中R、R1、R2、R3、G和n具有规范中报告的含义，适当地标记有诊断成像团或甚至放射治疗团。该发明还涉及它们的制备方法，包括它们的药物组合物和它们作为诊断成像剂或放射治疗剂的用途。
• ARYL-SULPHONAMIDIC DIMERS AS METALLOPROTEASES INHIBITORS
  申请人：Bracco Imaging S.p.A

  公开号：EP2149568A1

  公开（公告）日：2010-02-03

  The invention relates to dimeric aryl-sulphonamido compounds endowed with inhibitory activity against metalloproteases MMP, having formula (I) below          (M)-L-(M')     (I) wherein M and M', the same or different from each other, represent the residues of the mctalloprotcascs inhibitors of formula (II) wherein R, R1, R2, R3, G and n have the meanings reported in the specification; the invention also refers to the process for their preparation, to pharmaceutical compositions comprising them and to their use as therapeutic agents, particularly in the treatment of degenerative disorders.

  该发明涉及具有对金属蛋白酶MMP具有抑制活性的二聚芳基磺胺基化合物，其具有以下式(I)：(M)-L-(M')，其中M和M'，相同或不同，代表具有以下式(II)金属蛋白酶抑制剂的残基，其中R、R1、R2、R3、G和n在说明书中有所述；该发明还涉及其制备方法，包括它们的药物组合物以及它们作为治疗剂的用途，特别是在治疗退行性疾病方面。
• Compounds having aryl-sulphonamidic structure useful as metalloproteases inhibitors
  申请人：Bracco S.P.A.

  公开号：EP1972617A1

  公开（公告）日：2008-09-24

  The invention relates to aryl-sulphonamido compounds endowed with inhibitory activity against metallo proteases MMP, having formula (I) below wherein R, R1, R2, R3, R4, R5, n and m have the meanings reported in the specification; the invention also refers to the process for their preparation, to pharmaceutical compositions comprising them and to their use as therapeutic agents, particularly in the treatment of degenerative disorders.

  本发明涉及具有对金属蛋白酶MMP具有抑制活性的芳基磺胺基化合物，其具有以下式（I）其中R、R1、R2、R3、R4、R5、n和m具有规范中报告的含义；本发明还涉及它们的制备方法，包括它们的制药组合物以及它们作为治疗剂的用途，特别是在治疗退行性疾病方面。
• Potent Arylsulfonamide Inhibitors of Tumor Necrosis Factor-α Converting Enzyme Able to Reduce Activated Leukocyte Cell Adhesion Molecule Shedding in Cancer Cell Models
  作者：Elisa Nuti、Francesca Casalini、Stanislava I. Avramova、Salvatore Santamaria、Marina Fabbi、Silvano Ferrini、Luciana Marinelli、Valeria La Pietra、Vittorio Limongelli、Ettore Novellino、Giovanni Cercignani、Elisabetta Orlandini、Susanna Nencetti、Armando Rossello

  DOI：10.1021/jm901868z

  日期：2010.3.25

  useful target in anticancer therapy. Herein, we report the synthesis and biological evaluation of new ADAM-17 inhibitors containing an arylsulfonamidic scaffold. Among the new potential inhibitors, two very promising compounds 17 and 18 were discovered, with a nanomolar activity for ADAM-17 isolated enzyme. These compounds proved to be also the most potent in inhibiting soluble ALCAM release in cancer

  活化的白细胞粘附分子（ALCAM）在肿瘤生物学和进展中起着重要作用。我们以前的研究表明，ALCAM在上皮性卵巢癌（EOC）细胞表面表达，并通过ADAM-17介导的脱落以可溶形式释放。此过程与EOC细胞的运动性和侵袭性有关，ADAM-17的非特异性抑制剂会降低EOC的细胞运动性和侵袭性。因此，ADAM-17可能代表抗癌治疗的新靶标。在此，我们报告了含有芳基磺酰胺基支架的新型ADAM-17抑制剂的合成和生物学评估。在新的潜在抑制剂中，两种非常有前途的化合物17和18被发现具有ADAM-17分离酶的纳摩尔活性。这些化合物被证明也是抑制癌细胞中可溶性ALCAM释放的最有效剂，对A2774和SKOV3细胞系表现出纳摩尔活性。
• Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models
  作者：Elisa Nuti、Francesca Casalini、Salvatore Santamaria、Marina Fabbi、Grazia Carbotti、Silvano Ferrini、Luciana Marinelli、Valeria La Pietra、Ettore Novellino、Caterina Camodeca、Elisabetta Orlandini、Susanna Nencetti、Armando Rossello

  DOI：10.1021/jm4011753

  日期：2013.10.24

  Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nivi on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.