7-氨基-3-氯甲基-3-头孢唑啉-4-羧酸对甲氧苄盐酸盐 | 113479-65-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 7-氨基-3-氯甲基-3-头孢唑啉-4-羧酸对甲氧苄盐酸盐
• 中文别名: 7-氨基-3-氯-3-头孢唑啉-4羧酸对甲氧苄盐酸盐；ACLE.HCl
• 英文名称: para-methoxybenzyl (6R,7R)-7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride
• 英文别名: 7-amino-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester hydrochloride；[(6R,7R)-3-(chloromethyl)-2-[(4-methoxyphenyl)methoxycarbonyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]azanium;chloride
• CAS: 113479-65-5
• 化学式: C₁₆H₁₇ClN₂O₄S*ClH
• 分子量: 405.302
• InChiKey: LYIIGHOYDRRHAJ-XRZFDKQNSA-N

物化性质

• 熔点：
  155-157°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P261,P272,P280,P284,P302+P352,P304+P340+P312
• 危险品运输编号：
  2811
• 危险性描述：
  H317,H334
• 储存条件：
  室温且干燥

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 7-Amino-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester, HCl
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 7-Amino-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester, HCl
CAS number: 113479-65-5

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, under −20◦C.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C16H17ClN2O4S.ClH
Molecular weight: 405.3

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride, sulfur oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

本品为头孢唑啉的中间体，可用于制备抗菌剂。

反应信息

• 作为反应物：
  描述：

  7-氨基-3-氯甲基-3-头孢唑啉-4-羧酸对甲氧苄盐酸盐 在 盐酸 、 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 sodium iodide 作用下， 以 四氢呋喃 、 乙酸乙酯 、 丙酮 为溶剂， 反应 16.33h， 生成 4-methoxyphenylmethyl 7-<(Z)-2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetamido>-3-<(Z)-3-(N-methylcarbamoyloxy)-1-propenyl>-3-cephem-4-carboxylate
  参考文献：
  名称：

  口服活性头孢菌素的研究。二。新的[（E）或（Z）3-取代的氨基甲酰氧基] -1-丙烯基头孢菌素的合成及构效关系。

  摘要：

  为了寻找一种具有良好平衡的抗菌谱，良好的口服吸收性和长血浆半衰期的新型口服头孢菌素，一系列氧亚氨基氨基噻唑基3-[（E）-或（Z）-N-取代的氨基甲酰氧基]丙烯基头孢烯合成并评估其抗菌活性和口服吸收性。氨基甲酰氧基的取代基在C-4位口服新戊酰氧基甲基酯后会影响其体外活性和生物利用度。在C-3位上具有N，N-二甲基氨基甲酰氧基部分的化合物显示出良好的口服吸收和均衡的抗菌活性。在该报告中，描述了3-（N-取代的氨基甲酰氧基）-丙烯基头孢烯的结构-活性关系和结构-口服吸收性关系。

  DOI：

  10.7164/antibiotics.47.1526
• 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 吡啶 、 五氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 7-氨基-3-氯甲基-3-头孢唑啉-4-羧酸对甲氧苄盐酸盐
  参考文献：
  名称：

  立体化学改变的头孢菌素作为新德里金属-β-内酰胺酶的有效抑制剂

  摘要：

  由β-内酰胺酶，特别是金属-β-内酰胺酶引起的抗生素耐药性已成为全球公共卫生的主要威胁。新德里金属-β-内酰胺酶-1 (NDM-1) 是最重要的金属-β-内酰胺酶之一；细菌病原体中 NDM-1 的产生显着降低了 β-内酰胺类抗生素的功效，包括挽救生命的碳青霉烯类抗生素。在这里，我们已经证明了立体化学改变的头孢菌素作为针对 NDM-1 的有效抑制剂，以及 NDM 的突变体。对 20 多种头孢菌素类似物的结构和活性关系 (SAR) 研究表明，头孢菌素的立体化学和 7 位和 3' 位的取代基对抑制 NDM-1 的活性至关重要，最佳化合物1u的 IC为 500.13 μM。此外，已经获得了NDM-1和1u的晶体复合物，表明这种头孢菌素衍生物通过形成相对稳定的水解产物-NDM-1中间体来抑制酶活性。这项研究的发现可能为将头孢菌素（β-内酰胺酶的天然底物）转化为有效的 NDM-1 抑制剂以对抗抗生素耐药性铺平道路。

  DOI：

  10.1016/j.ejmech.2022.114174
• 作为试剂：
  描述：

  (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)acetic methanesulfonic anhydride 、 7-氨基-3-氯甲基-3-头孢唑啉-4-羧酸对甲氧苄盐酸盐 在 7-氨基-3-氯甲基-3-头孢唑啉-4-羧酸对甲氧苄盐酸盐 作用下， 生成 4-methoxybenzyl 7β-[(Ζ)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-chloromethyl-3-cephem-4-carboxylate
  参考文献：
  名称：

  制备头孢烯化合物的中间体及其晶体

  摘要：

  本发明公开了制备头孢烯化合物的中间体及其晶体,具体而言涉及制备头孢特咯瓒的中间体，中间体的晶体以及制备头孢特咯瓒的方法。使用固体形式(无定形和晶体)的中间体来制备硫酸头孢特咯瓒显著降低了杂质的含量，所得产物收率高、纯度好、后处理简单，更适合工业化生产。

  公开号：

  CN107556328A

文献信息

• [EN] CEPHEM COMPOUNDS<br/>[FR] CEPHEMES
  申请人：FUJISAWA PHARMACEUTICAL CO

  公开号：WO2005027909A1

  公开（公告）日：2005-03-31

  The present invention relates to a compound of the formula [I]: wherein R1 is lower alkyl or hydroxy (lower) alkyl, and R2 is hydrogen or amino protecting group, or R1 and R2 are bonded together and form lower alkylene ; R3 is -A-R6 wherein A is bond, -NHCO-(CH2CO)n-, lower alkylene, -NH-CO-CO- or the like, and R6 is (a) ou (b) wherein R7, R8, R9 and R10 are independently amino, guanidino, amidino or the like ; R4 is carboxy or protected carboxy; and R5 is amino or protected amino, or a pharmaceutically acceptable salt thereof, a process for preparing a compound of the formula [I], and a pharmaceutical composition comprising a compound of the formula [I] in admixture with a pharmaceutically acceptable carrier.

  本发明涉及一种公式的化合物[I]：其中R1是低级烷基或羟基（低级）烷基，R2是氢或氨基保护基团，或者R1和R2连接并形成低级亚烷基；R3是-A-R6，其中A是键，-NHCO-(CH2CO)n-，低级亚烷基，-NH-CO-CO-或类似物质，R6是(a)或(b)其中R7，R8，R9和R10是独立的氨基，胍基，脒基或类似物质；R4是羧基或受保护的羧基；R5是氨基或受保护的氨基，或药用可接受的盐，一种制备公式化合物[I]的方法，以及一种包括与药用可接受载体混合的公式化合物[I]的药物组合物。
• 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。
• Synthesis of Novel Macrocyclic Compounds Derived from Ceftriaxone
  作者：Masayuki Sano、Hiroyuki Shimaoka、Naoki Kohira、Yuki Murakami、Hitoshi Murai、Hidenori Yoshizawa

  DOI：10.1246/cl.200607

  日期：2020.12.5

  Macrocyclization can help improve pharmacological activity, metabolic stability, cell permeability and oral absorption to create better drug candidates. For example, enhancing the oral absorption o...

  大环化可以帮助提高药理活性、代谢稳定性、细胞渗透性和口服吸收，以创造更好的候选药物。例如，提高口服吸收...
• [EN] CROSS-LINKED GLYCOPEPTIDE-CEPHALOSPORIN ANTIBIOTICS<br/>[FR] ANTIBIOTIQUES A BASE DE CEPHALOSPORINE GLYCOPEPTIDIQUE RETICULEE
  申请人：THERAVANCE INC

  公开号：WO2003099858A1

  公开（公告）日：2003-12-04

  This invention provides cross-linked glycopeptide - cephalosporin compounds of formula I and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds. As a vancomycin analogue is employed in the compounds of the present invention, the point of attachment for the linking moiety is amino acid 7 (AA-7) at position C-29. This position is also sometimes referred to as the '7d' or the 'resorcinol' position of vancomycin. Formula (I)

  这项发明提供了公式I的交联糖肽 - 头孢菌素化合物及其药学上可接受的盐，这些化合物可用作抗生素。该发明还提供了含有这种化合物的药物组合物；使用这种化合物治疗哺乳动物细菌感染的方法；以及用于制备这种化合物的过程和中间体。由于本发明化合物中采用了万古霉素类似物，连接基团的连接点是氨基酸7（AA-7）位于C-29位置。这个位置有时也被称为万古霉素的“7d”或“间苯二酚”位置。公式（I）
• [EN] SYNTHESIS OF CEPHALOSPORIN COMPOUNDS<br/>[FR] SYNTHÈSE DE COMPOSÉS DE CÉPHALOSPORINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016025839A1

  公开（公告）日：2016-02-18

  Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising a palladium-catalyzed coupling reaction. Provided herein are methods for the synthesis of cephalosporin compounds of formula (I) employing a palladium-catalyzed alkylation reaction, as well as compositions related to the same. In an aspect, provided herein is a method for preparing a compound of formula (II), or a salt thereof, comprising the step of admixing, e.g., reacting, a compound of formula (III), or a salt thereof, with a nucleophile (Nuc) in the presence of reagents comprising: (a) a palladium source; and (b) a palladium-binding ligand, to form a compound of formula (II), or a salt thereof.

  本文提供了一种合成头孢菌素抗生素化合物的方法，包括钯催化的偶联反应。本文提供了一种利用钯催化的烷基化反应合成式(I)头孢菌素化合物的方法，以及相关的组合物。在一个方面，本文提供了一种制备式(II)化合物或其盐的方法，包括混合，例如，将式(III)化合物或其盐与核苷（Nuc）在存在以下试剂的情况下进行反应：(a) 钯源；和(b) 钯配体，以形成式(II)化合物或其盐。