(+)-pinanediol chloromethaneboronate | 110744-85-9

• 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 chloromethaneboronate
• 英文别名: (+)-2,3-pinanediyl (chloromethyl)boronate；4-chloromethyl-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]-decane；(S)-pinanediol (chlormethyl)boronate；(1S,2S,6R,8S)-4-(chloromethyl)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decane
• CAS: 110744-85-9
• 化学式: C₁₁H₁₈BClO₂
• 分子量: 228.527
• InChiKey: DBMHAFMCTIBVTN-CKEKPRIKSA-N

物化性质

• 沸点：
  252.8±23.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.49
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-pinanediol chloromethaneboronate 在 甲醇 、 正丁基锂 、 sodium azide 、 四丁基碘化铵 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 生成
  参考文献：
  名称：

  Biochemical and Structural Analysis of Inhibitors Targeting the ADC-7 Cephalosporinase of Acinetobacter baumannii

  摘要：

  beta-Lactam resistance in Acinetobacter baumannii presents one of the greatest challenges to contemporary antimicrobial chemotherapy. Much of this resistance to cephalosporins derives from the expression of the class C beta-lactamase enzymes, known as Acinetobacter-derived cephalosporinases (ADCs). Currently, beta-lactamase inhibitors are structurally similar to beta-lactam substrates and are not effective inactivators of this class C cephalosporinase. Herein, two boronic acid transition state inhibitors (BATSIs S02030 and SM23) that are chemically distinct from beta-lactams were designed and tested for inhibition of ADC enzymes. BATSIs SM23 and S02030 bind with high affinity to ADC-7, a chromosomal cephalosporinase from Acinetobacter baumannii (K-i = 21.1 +/- 1.9 nM and 44.5 +/- 2.2 nM, respectively). The X-ray crystal structures of ADC-7 were determined in both the apo form (1.73 angstrom resolution) and in complex with S02030 (2.0 angstrom resolution). In the complex, S02030 makes several canonical interactions: the O1 oxygen of S02030 is bound in the oxyanion hole, and the R1 amide group makes key interactions with conserved residues Asn152 and Gln120. In addition, the carboxylate group of the inhibitor is meant to mimic the C-3/C-4 carboxylate found in beta-lactams. The C-3/C-4 carboxylate recognition site in class C enzymes is comprised of Asn346 and Arg349 (AmpC numbering), and these residues are conserved in ADC-7. Interestingly, in the ADC-7/S02030 complex, the inhibitor carboxylate group is observed to interact with Arg340, a residue that distinguishes ADC-7 from the related class C enzyme AmpC. A thermodynamic analysis suggests that Delta H driven compounds may be optimized to generate new lead agents. The ADC-7/BATSI complex provides insight into recognition of non-beta-lactam inhibitors by ADC enzymes and offers a starting point for the structure-based optimization of this class of novel beta-lactamase inhibitors against a key resistance target.

  DOI：

  10.1021/bi500887n
• 作为产物：
  描述：

  diisopropyl (chloromethane)boranate 、 (1S,2S,3R,5S)-(+)-2,3-蒎烷二醇 以 乙醚 为溶剂， 以98%的产率得到(+)-pinanediol chloromethaneboronate
  参考文献：
  名称：

  Synthesis and evaluation of novel α-amino cyclic boronates as inhibitors of HCV NS3 protease

  摘要：

  We have designed and synthesized a novel series of alpha-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described.

  DOI：

  10.1016/j.bmcl.2010.04.129

文献信息

• [EN] BETA-LACTAMASE INHIBITORS<br/>[FR] INHIBITEURS DE BÊTA-LACTAMASES
  申请人：VENATORX PHARMACEUTICALS INC

  公开号：WO2017044828A1

  公开（公告）日：2017-03-16

  Described herein are compounds and compositions that modulate the activity of beta -lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.

  本发明描述了能够调节β-内酰胺酶活性的化合物和组合物。在某些实施例中，本发明所描述的化合物可抑制β-内酰胺酶。在某些实施例中，本发明所描述的化合物可用于治疗细菌感染。
• COMPOSITIONS AND METHODS OF TREATING OF BACTERIAL INFECTIONS WITH BETA-LACTAMASE INHIBITORS
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US20170065626A1

  公开（公告）日：2017-03-09

  A method of treating a bacterial infection in a subject in need thereof includes administering to the subject therapeutically effective amounts of at least one β-lactam antibiotic and at least one triazolylmethyl boronic acid.

  治疗需要的受试者体内细菌感染的方法包括向受试者投予至少一种β-内酰胺类抗生素和至少一种三唑基甲硼酸的治疗有效剂量。
• Mattesen, Donald S.; Kandil, Ali A.; Soundararajan, Raman, Journal of the American Chemical Society, 1990, vol. 112, # 10, p. 3964 - 3969
  作者：Mattesen, Donald S.、Kandil, Ali A.、Soundararajan, Raman

  DOI：——

  日期：——
• Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors
  作者：Emilia Caselli、Chiara Romagnoli、Roza Vahabi、Magdalena A. Taracila、Robert A. Bonomo、Fabio Prati

  DOI：10.1021/acs.jmedchem.5b00341

  日期：2015.7.23

  Boronic acid transition-state inhibitors (BAT-SIs) represent one of the most promising classes of beta-lactamase inhibitors. Here we describe a new class of BATSIs, namely, 1-amido-2-triazolylethaneboronic acids, which were synthesized by combining the asymmetric homologation of boronates with copper-catalyzed azide-alkyne cycloaddition for the stereoselective insertion of the amido group and the regioselective formation of the 1,4-disubstituted triazole, respectively. This synthetic pathway, which avoids intermediate purifications, proved to be flexible and efficient, affording in good yields a panel of 14 BATSIs bearing three different R1 amide side chains (acetamido, benzylamido, and 2-thienylacetamido) and Several R substituents on the triazole. This small library was tested against two clinically relevant class C beta-lactamases from Enterobacter spp. and Pseudomonas aeruginosa. The K-i value of the best compound (13a) was as low as 4 nM with significant reduction of bacterial resistance to the combination of cefotaxime/13a.
• MATTESON, DONALD S.;PETERSON, MARK L., J. ORG. CHEM., 52,(1987) N 23, 5116-5121
  作者：MATTESON, DONALD S.、PETERSON, MARK L.

  DOI：——

  日期：——