(+)-pinanediol (R)-1-amino-2-phenylethane-1-boronate trifluoroacetate salt | 514820-49-6

• 物质功能分类: 化学试剂 - 有机试剂 - 硼烷
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-pinanediol (R)-1-amino-2-phenylethane-1-boronate trifluoroacetate salt
• 英文别名: (R)-2-phenyl-1-((3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)ethanamine 2,2,2-trifluoroacetate；(1R)-2-phenyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethanamine;2,2,2-trifluoroacetic acid
• CAS: 514820-49-6
• 化学式: C₂HF₃O₂*C₁₈H₂₆BNO₂
• 分子量: 413.245
• InChiKey: YJRYQGLPPMUWRO-SKAYQWHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (+)-pinanediol (R)-1-amino-2-phenylethane-1-boronate trifluoroacetate salt 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 苯硼酸 作用下， 以 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 1.42h， 生成
  参考文献：
  名称：

  Structural Optimization, Biological Evaluation, and Application of Peptidomimetic Prostate Specific Antigen Inhibitors

  摘要：

  Prostate-specific antigen (PSA) is a serine protease produced at high levels by normal and malignant prostate epithelial cells that is used extensively as a biomarker in the clinical management of prostate cancer. To better understand PSA's role in prostate cancer progression, we prepared a library of peptidyl boronic acid-based inhibitors. To enhance selectivity for PSA vs other serine proteases, we modified the P1 site of the inhibitors to incorporate a bromopropylglycine group. This allowed the inhibitors to participate in halogen bond formation with the serine found at the bottom of the specificity pocket. The best of these Ahx-FSQn(boro)Bpg had PSA K-i of 72 nM and chymotrypsin K-i of 580 nM. In vivo studies using PSA-producing xenografts demonstrated that candidate inhibitors had minimal effect on growth but significantly altered serum levels of PSA. Biodistribution of I-125 labeled peptides showed low levels of uptake into tumors compared to other normal tissues.

  DOI：

  10.1021/jm301718c
• 作为产物：
  描述：

  (+)-pinanediol phenylmethyl-1-boronate 在 正丁基锂 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 3.34h， 生成 (+)-pinanediol (R)-1-amino-2-phenylethane-1-boronate trifluoroacetate salt
  参考文献：
  名称：

  Structural Optimization, Biological Evaluation, and Application of Peptidomimetic Prostate Specific Antigen Inhibitors

  摘要：

  Prostate-specific antigen (PSA) is a serine protease produced at high levels by normal and malignant prostate epithelial cells that is used extensively as a biomarker in the clinical management of prostate cancer. To better understand PSA's role in prostate cancer progression, we prepared a library of peptidyl boronic acid-based inhibitors. To enhance selectivity for PSA vs other serine proteases, we modified the P1 site of the inhibitors to incorporate a bromopropylglycine group. This allowed the inhibitors to participate in halogen bond formation with the serine found at the bottom of the specificity pocket. The best of these Ahx-FSQn(boro)Bpg had PSA K-i of 72 nM and chymotrypsin K-i of 580 nM. In vivo studies using PSA-producing xenografts demonstrated that candidate inhibitors had minimal effect on growth but significantly altered serum levels of PSA. Biodistribution of I-125 labeled peptides showed low levels of uptake into tumors compared to other normal tissues.

  DOI：

  10.1021/jm301718c

文献信息

• Target Validation and Identification of Novel Boronate Inhibitors of the <i>Plasmodium falciparum</i> Proteasome
  作者：Stanley C. Xie、David L. Gillett、Natalie J. Spillman、Christopher Tsu、Madeline R. Luth、Sabine Ottilie、Sandra Duffy、Alexandra E. Gould、Paul Hales、Benjamin A. Seager、Carlie L. Charron、Frank Bruzzese、Xiaofeng Yang、Xiansi Zhao、Shih-Chung Huang、Craig A. Hutton、Jeremy N. Burrows、Elizabeth A. Winzeler、Vicky M. Avery、Lawrence R. Dick、Leann Tilley

  DOI：10.1021/acs.jmedchem.8b01161

  日期：2018.11.21

  potential antimalarial drug target for compounds with activity against multiple life cycle stages. We screened a library of human proteasome inhibitors (peptidyl boronic acids) and compared activities against purified P. falciparum and human 20S proteasomes. We chose four hits that potently inhibit parasite growth and show a range of selectivities for inhibition of the growth of P. falciparum compared

  疟原虫蛋白酶体代表具有针对多个生命周期阶段的活性的化合物的潜在抗疟疾药物靶标。我们筛选了人类蛋白酶体抑制剂（肽基硼酸）文库，并比较了其对纯化的恶性疟原虫和人类20S蛋白酶体的活性。我们选择了四个能有效抑制寄生虫生长并显示出与人类细胞系相比可抑制恶性疟原虫生长的选择性的命中物。选择恶性疟原虫对临床使用的蛋白酶体抑制剂硼替佐米具有体外抗性，并应用全基因组测序来鉴定蛋白酶体β5亚基中的突变。活性位点分析揭示了抑制剂功能，可以保留针对硼替佐米耐药株的有效活性。底物分析显示P. 恶性疟原虫20S蛋白酶体活性位点的偏好，将有助于尝试设计更多选择性抑制剂。这项工作为鉴定选择性靶向恶性疟原虫蛋白酶体的抗疟药物前导提供了起点。
• Synthesis of boronic acid derivatives of tyropeptin: Proteasome inhibitors
  作者：Takumi Watanabe、Isao Momose、Masatoshi Abe、Hikaru Abe、Ryuichi Sawa、Yoji Umezawa、Daishiro Ikeda、Yoshikazu Takahashi、Yuzuru Akamatsu

  DOI：10.1016/j.bmcl.2009.02.117

  日期：2009.4

  Boronic acid derivatives of tyropeptin were synthesized with TP-110 as the lead compound. Due to the lability of the aminoboronic acid moiety, careful design of the deprotection and coupling sequence was required. Liquid-liquid partition chromatography was found to be a powerful tool for purification of compounds of this class. The obtained derivatives showed potent inhibitory activities against the human 20S proteasome in vitro. (C) 2009 Elsevier Ltd. All rights reserved.