3-iodomethyl-7-phenylacetylamido-3-cephem-4-carboxylic acid p-methoxybenzyl ester | 101156-40-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 3-iodomethyl-7-phenylacetylamido-3-cephem-4-carboxylic acid p-methoxybenzyl ester
• 英文别名: 3-iodomethyl-7-phenylacetamido-Δ³-cephem-4-carboxylate；3-iodomethyl cephalosporin；(6R,7R)-4-methoxybenzyl-3-(iodomethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate；4-methoxybenzyl 3-iodomethyl-7-(2-phenylacetamido)-3-cephem-4-carboxylate；3-iodomethyl-7-phenylacetylaminocephalosporanic acid p-methoxybenzyl ester；p-methoxybenzyl 3-iodomethyl-7-(2-phenylacetamido)-3-cephem-4-carboxylate；(4-methoxyphenyl)methyl (6R,7R)-3-(iodomethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 101156-40-5
• 化学式: C₂₄H₂₃IN₂O₅S
• 分子量: 578.428
• InChiKey: LMIFMXLOTVQYTB-NFBKMPQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-iodomethyl-7-phenylacetylamido-3-cephem-4-carboxylic acid p-methoxybenzyl ester 在 青霉素(酰胺)酶 、 硫酸 、 苯酚 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 11.0h， 生成 硫酸头孢匹罗
  参考文献：
  名称：

  One-Pot Synthesis of Cefpirome Sulfate from GCLE

  摘要：

  [image omitted] Cefpirome was synthesized in 37.7% overall yield from 3-chloromethyl-7-phenylacetylamino cephalosporanic acid p-methoxybenzyl ester (GCLE) by sequential substitution of C-3 chloride with iodide and 2,3-cyclopentenopyridine, followed by a one-pot procedure including deprotection of carboxyl group, hydrolysis of 7-phenylacetamido, and reaction with 2-mercaptobenzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate (MAEM). The reaction conditions were as follows: obtained from GCLE at low temperature (-5 to 0 degrees C) and absence of light, 3-iodomethyl-7-phenylacetylamino cephalosporanic acid p-methoxybenzyl ester (GILE) without purification was reacted directly with 2,3-cyclopentenopyridine, in which the molar ratio of GCLE, NaI, and 2,3-cyclopentenopyridine was 1:2:4, and the molar ratio of the resulting compound p-methoxybenzyl 7-phenylacetylamido-3-(2,3-cyclopenteno-1-pyridinio)methyl-3-cephem-4-carboxylate iodide and MAEM was 1:1.1. The structure of the intermediate and the target compound obtained were determined by nuclear magnetic resonance spectra and mass spectroscopy.

  DOI：

  10.1080/00397911003629499
• 作为产物：
  描述：

  7-苯乙酰氨基-3-氯甲基-4-头孢烷酸对甲氧基苄酯 在 sodium iodide 作用下， 以 丙酮 为溶剂， 以93%的产率得到3-iodomethyl-7-phenylacetylamido-3-cephem-4-carboxylic acid p-methoxybenzyl ester
  参考文献：
  名称：

  Aerobic Oxidation of 3-Iodomethyl-Δ³-cephem-4-carboxylate to 3-Formyl-Δ³-cephem-4-carboxylate through 3-Hydroperoxymethyl-Δ³-cephem-4-carboxylate

  摘要：

  3-iodomethyl-8-oxo-7-phenylacetamido-5-thia-1-azabicyclo[4.2.在磷钼酸存在下，N-甲基-2-吡咯烷酮中的 3-碘甲基-8-氧代-7-苯乙酰胺基-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸酯（3-碘甲基-7-苯乙酰胺基-Δ3-cephem-4-羧酸酯）主要得到相应的 3-甲酰基-Δ3-cephem-4-羧酸酯，而在碘化钾存在下的类似有氧氧化则得到 3-羟甲基-Δ3-cephem-4-羧酸酯作为主要产物。3-hydroperoxymethyl-Δ3-cephem-4-carboxylate 作为有氧氧化的主要产物被分离出来，随后通过磷钼酸脱水转化为 3-formyl-Δ3-cephem-4-carboxylate 或通过碘化钾还原转化为 3-hydroxymethyl-Δ3-cephem-4-carboxylate 。

  DOI：

  10.1246/bcsj.69.229

文献信息

• NOVEL CEPHALOSPORIN DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：CHO Young Lag

  公开号：US20120264727A1

  公开（公告）日：2012-10-18

  The present invention relates to novel cephalosporin derivatives represented by Chemical Formula 1. Wherein, X, Y, L, R 1 , and R 2 are as same as defined in the description of the invention. The present invention also relates to pharmaceutical antibiotic compositions comprising a novel celphalosporin derivative represented by Chemical Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient. According to the present invention, novel cephalosporin derivatives, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient for the broad spectrum of antibiotic resistant, low toxicity, particularly in Gram-negative bacteria, which can be useful with strong antimicrobial activity.

  本发明涉及由化学公式1表示的新型头孢菌素衍生物。其中，X、Y、L、R1和R2与发明描述中定义的相同。本发明还涉及包含由化学公式1表示的新型头孢菌素衍生物、前药、水合物、溶剂化物、异构体或药用可接受盐作为有效成分的药物抗生素组合物。根据本发明，新型头孢菌素衍生物、前药、水合物、溶剂化物、异构体或药用可接受盐作为广谱抗生素耐药、低毒性的有效成分，特别是在革兰氏阴性细菌中，可以具有强大的抗菌活性。
• Novel Cephalosporin Conjugates Display Potent and Selective Inhibition of Imipenemase-Type Metallo-β-Lactamases
  作者：Kamaleddin H. M. E. Tehrani、Nicola Wade、Vida Mashayekhi、Nora C. Brüchle、Willem Jespers、Koen Voskuil、Diego Pesce、Matthijs J. van Haren、Gerard J. P. van Westen、Nathaniel I. Martin

  DOI：10.1021/acs.jmedchem.1c00362

  日期：2021.7.8

  enzymatic hydrolysis of the β-lactam ring was observed, it was not accompanied by inhibitor release. Nonetheless, the cephalosporin prodrugs, especially thiomandelic acid conjugate (8), demonstrated potent inhibition of IMP-type MBLs. In addition, conjugate 8 was also found to greatly reduce the minimum inhibitory concentration of meropenem against IMP-producing bacteria. The results of kinetic experiments

  为了探索β-内酰胺酶降解头孢菌素的水解机制，我们设计并合成了一系列新型头孢菌素前药，旨在以时空控制的方式递送金属β-内酰胺酶（MBL）的巯基抑制剂。虽然观察到 β-内酰胺环的酶促水解，但不伴随抑制剂的释放。尽管如此，头孢菌素前药，尤其是硫扁桃酸偶联物 ( 8 )，显示出对 IMP 型MBL 的有效抑制。此外，共轭8还发现美罗培南对产生 IMP 的细菌的最小抑制浓度大大降低。动力学实验结果表明，这些前药通过充当缓慢翻转的底物来抑制 IMP 型 MBL。构效关系研究表明，8 的苯基和羧基部分对其效力至关重要。此外，建模研究表明8的硫扁桃酸部分与 IMP 活性位点内的 Trp28 的有效相互作用可能有助于其效力和选择性。
• Chromophore-Linked Substrate (CLS405): Probing Metallo-β-Lactamase Activity and Inhibition
  作者：Anne Makena、Sander S. van Berkel、Clarisse Lejeune、Raymond J. Owens、Anil Verma、Ramya Salimraj、James Spencer、Jürgen Brem、Christopher J. Schofield

  DOI：10.1002/cmdc.201300350

  日期：2013.12

  5‐dioxide (CLS405) was synthesised in a three‐step protocol. CLS405 was then characterised spectroscopically, and its stability and kinetic properties evaluated. With a Δλmax value of 100 nm between the parent and hydrolysis product, a higher analytical accuracy is possible with CLS405 than with commonly used chromogenic substrates. The use of CLS405 in assays was validated by MBL activity measurements

  丝氨酸和金属β-内酰胺酶对几乎所有β-内酰胺类抗生素的临床使用构成威胁，包括青霉素、头孢菌素和碳青霉烯类。开发金属-β-内酰胺酶 (MBL) 抑制剂的努力需要合适的筛选平台，以便快速测定 β-内酰胺酶活性和有效抑制。不幸的是，目前可用的平台并不适合此目的。MBL 抑制剂鉴定的进一步进展需要廉价且广泛适用的检测方法。本文描述了一种廉价且稳定的显色底物的鉴定，该底物适用于临床相关 MBL 的测定。(6 R ,7 R)-3-((4-Nitrophenoxy)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxy acid 5,5 ‐二氧化物 (CLS405) 采用三步法合成。然后对 CLS405 进行光谱表征，并评估其稳定性和动力学特性。由于母体和水解产物之间的 Δ λ最大值为 100 nm，CLS405
• New C-3′ hydroxamate-substituted and more lipophilic cyclic hydroxamate cephalosporin derivatives as a potential new generation of selective antimicrobial agents
  作者：Marvin J. Miller、Gaiying Zhao、Sergei Vakulenko、Scott Franzblau、Ute Möllmann

  DOI：10.1039/b612475e

  日期：——

  Syntheses of a series of new C-3′ hydroxamate-substituted cephalosporin derivatives with potent antibacterial and media-dependent anti-TB activity are described.

  描述了一系列新的C-3′羟肟酸取代的头孢菌素衍生物的合成，这些衍生物具有强大的抗菌活性和介质依赖的抗结核活性。
• Synthesis of cephalosporin-3′-diazeniumdiolates: biofilm dispersing NO-donor prodrugs activated by β-lactamase
  作者：Nageshwar Rao Yepuri、Nicolas Barraud、Nasim Shah Mohammadi、Bharat G. Kardak、Staffan Kjelleberg、Scott A. Rice、Michael J. Kelso

  DOI：10.1039/c3cc40869h

  日期：——

  Use of biofilm dispersing NO-donor compounds in combination with antibiotics has emerged as a promising new strategy for treating drug-resistant bacterial biofilm infections. This paper details the synthesis and preliminary evaluation of six cephalosporin-3'-diazeniumdiolates as biofilm-targeted NO-donor prodrugs. Each of the compounds is shown to selectively release NO following reaction with the

  生物膜分散NO供体化合物与抗生素的结合使用已成为治疗耐药细菌生物膜感染的有前途的新策略。本文详细介绍了六种头孢菌素3'-二氮杂二醇盐作为生物膜靶向NO供体前药的合成和初步评估。已显示每种化合物在与细菌特异性酶β-内酰胺酶反应后选择性释放NO，并在体外触发铜绿假单胞菌生物膜的分散。