(+)-pinanediol 1-chloro-pentyl-1-boronate hydrochloride

• 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 1-chloro-pentyl-1-boronate hydrochloride
• 英文别名: (1R)-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentan-1-amine;hydrochloride
• 化学式: C₁₅H₂₈BNO₂*ClH
• 分子量: 301.665
• InChiKey: UWOAYLQMKWTEGE-CDVUYJLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.19
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  44.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-pinanediol 1-chloro-pentyl-1-boronate hydrochloride 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors

  摘要：

  Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and born-norleucine (boro-Nle) in the P1 position were synthesized. Relative to born-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.076
• 作为产物：
  描述：

  (1S,2S,3R,5S)-(+)-2,3-蒎烷二醇 在 盐酸 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 39.0h， 生成 (+)-pinanediol 1-chloro-pentyl-1-boronate hydrochloride
  参考文献：
  名称：

  Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors

  摘要：

  Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and born-norleucine (boro-Nle) in the P1 position were synthesized. Relative to born-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.076

文献信息

• Structure-Based Design of Selective LONP1 Inhibitors for Probing <i>In Vitro</i> Biology
  作者：Laura J. Kingsley、Xiaohui He、Matthew McNeill、John Nelson、Victor Nikulin、Zhiwei Ma、Wenshuo Lu、Vicki W. Zhou、Mari Manuia、Andreas Kreusch、Mu-Yun Gao、Darbi Witmer、Mei-Ting Vaillancourt、Min Lu、Sarah Greenblatt、Christian Lee、Ajay Vashisht、Steven Bender、Glen Spraggon、Pierre-Yves Michellys、Yong Jia、Jacob R. Haling、Gérald Lelais

  DOI：10.1021/acs.jmedchem.0c02152

  日期：2021.4.22

  of LONP1 in human biology and disease, very few LONP1 inhibitors have been described in the literature. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Our efforts led to several nanomolar LONP1 inhibitors with little to no activity against the 20S proteasome

  LONP1是一种AAA +蛋白酶，可通过去除受损或错误折叠的蛋白质来维持线粒体的体内平衡。LONP1的活性和表达升高会促进癌细胞的增殖和对凋亡诱导剂的抗性。尽管LONP1在人类生物学和疾病中很重要，但文献中几乎没有描述过LONP1抑制剂。在这里，我们报告使用基于结构的药物设计以及结合各种抑制剂的人LONP1的第一个结构的选择性硼酸基LONP1抑制剂的发展。我们的努力导致了几种对20S蛋白酶体几乎没有活性的纳米摩尔LONP1抑制剂，它们是研究LONP1生物学的工具化合物。
• Design, Synthesis, Biological Evaluation, and Structure−Activity Relationship (SAR) Discussion of Dipeptidyl Boronate Proteasome Inhibitors, Part I: Comprehensive Understanding of the SAR of α-Amino Acid Boronates
  作者：Yongqiang Zhu、Xin Zhao、Xinrong Zhu、Gang Wu、Yuejie Li、Yuheng Ma、Yunxia Yuan、Jie Yang、Yang Hu、Li Ai、Qingzhi Gao

  DOI：10.1021/jm9005093

  日期：2009.7.23

  New series of dipeptidyl boronate inhibitors of 20S proteasome were designed and synthesized, The comprehensive understanding or the SAR was obtained by utilizing the variation of four substituents. From the screened compounds in enzyme, novel inhibitors 49 and 50 were identified to be highly potent druglike candidates with IC50 values of 1.2 and 1.6 nM, respectively, which showed better activities than the drug bortezomib on the market. Two hematologic human tumor cell lines, HL-60 and U266, were significantly sensitive to both candidates and showed nearly the same potency as the standard bortezomib with IC50 values less than 10 nM. But as for most of the eight human solid tumor cell lines, both candidates were more potent than the standard with the IC50 value range of 9.8-70 nM. The activity evaluation of the stereoisomers showed that changing R-isomers to S-isomers greatly reduced the potency and even induced inactivity.