(6R,7R)-7-Amino-3-chloro-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester | 53994-70-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (6R,7R)-7-Amino-3-chloro-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
• 英文别名: Diphenylmethyl 7beta-amino-3-chloro-3-cephem-4-carboxylate；benzhydryl (6R,7R)-7-amino-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 53994-70-0
• 化学式: C₂₀H₁₇ClN₂O₃S
• 分子量: 400.886
• InChiKey: BYPHSRGQSFWOOC-DNVCBOLYSA-N

物化性质

• 沸点：
  592.4±50.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  97.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6R,7R)-7-Amino-3-chloro-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 在 辛酸铑 三氟乙酸 、 methyloxirane 、 亚硝酸异戊酯 作用下， 生成 (R)-3-Chloro-7,8-dioxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  A convenient method for the production of 6-oxopenicillinates and 7-oxocephalosporinates

  摘要：

  A convenient and economical method for the preparation of 6-oxopenicillinates and 7-oxocephalosporinates from the corresponding amines is presented. These ketones are key intermediates in the synthesis of inhibitors of beta-lactamase and elastase. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00963-0
• 作为产物：
  描述：

  3-羟基头孢 在 吡啶 、 五氯化磷 、 三氯化磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (6R,7R)-7-Amino-3-chloro-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  Discovery of RWJ-54428 (MC-02,479), a New Cephalosporin Active Against Resistant Gram-positive Bacteria.

  摘要：

  描述了新型头孢菌素RWJ-54428（MC-02, 479）的发现，该药物对敏感和耐药的阳性革兰氏菌表现出良好的活性。通过对之前报道的3-苯基硫头孢MC-02, 331进行渐进式结构修饰，整体提高了对MRSA的效能，同时保持了其他关键特性，如可接受的溶解度和血清结合能力。对一系列密切相关化合物的体外活性和体内疗效进行评估，最终选择了RWJ-54428（MC-02, 479）进行进一步研究。

  DOI：

  10.7164/antibiotics.53.1272

文献信息

• Synthesis and structure-activity relationships of 7.BETA.-((Z)-2-(2-aminothiazol-4-yl)-3-(substituted)-2-propenoylamino)-3-cephems with C-3 substitutions.
  作者：KOJI ISHIKURA、TADASHI KUBOTA、KYOJI MINAMI、YOSHIO HAMASHIMA、HIROMU NAKASHIMIZU、KIYOSHI MOTOKAWA、YASUO KIMURA、HIDEAKI MIWA、TADASHI YOSHIDA

  DOI：10.7164/antibiotics.47.466

  日期：——

  Synthesis and biological activity of a series of 7 beta-[(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino]-3-cephe m-4-carboxylic acids with C-3 substitutions and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were

  一系列7个β-[（（Z）-2-（2-氨基噻唑-4-基）-3-（取代）-2-丙烯酰基氨基] -3- Cephe m-4-羧酸的合成及生物活性描述了-3个取代及其新戊酰氧基甲基酯。这些酸化合物对革兰氏阳性和革兰氏阴性细菌均显示出有效的抗菌活性。发现该系列中所选化合物的新戊酰氧基甲基酯在小鼠中被小肠很好吸收。最终选择了新戊酰氧基甲基7β-[（（Z）-2-（2-氨基噻唑-4-基）-2-戊烯酰氨基] -3-氨基甲酰氧基甲基-3-cephem-4-羧化酶盐酸盐水合物（S-1108）用于临床评估。
• Synthesis and in vitro antibacterial activity of new aminothiazole-oximepiperidone cephalosporins
  作者：Zhengwu Shen、Wei Xu、Jingfeng Yu、Lixia Chen、Jinghua Zhang、Sihan Sheng、Xun Dong、Hongzhu Bian

  DOI：10.1016/j.bmcl.2021.127928

  日期：2021.5

  Four new aminothiazole-oximepiperidone cephalosporins (10a-10d) were synthesized, with their in vitro antibacterial activities against hospital isolated Gram-negative bacteria assessed. The results showed that compounds 10a-10d effectively inhibit a variety of Gram-negative bacteria. Compound 10a was the most potent compound, with comparable activity as ceftazidime. The combination of compound 10a

  合成了四种新的氨基噻唑-肟哌啶酮头孢菌素 ( 10a-10d )，并评估了它们对医院分离的革兰氏阴性菌的体外抗菌活性。结果表明化合物10a-10d有效抑制多种革兰氏阴性菌。化合物10a是最有效的化合物，其活性与头孢他啶相当。化合物10a和 Avibactam的组合对几乎所有测试的细菌都非常有效，包括多重耐药肺炎克雷伯菌和鲍曼不动杆菌。与 Avycaz 相比，这种组合对产 ESBL 的肺炎克雷伯菌更有效. 因此，10a和 Avibactam的组合值得进一步研究。
• Substituted 7(.alpha.-amino phenylacetamido)cephem derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US04069324A1

  公开（公告）日：1978-01-17

  The invention relates to 7.beta.-[D-2-amino-2-(lower alkylsulphonylamino-phenyl)-acetylamino]-3-R-cephem-4-carboxylic acid, in which R denotes lower alkoxy or halogen with an atomic number of up to 35, and their salts, which compounds possess antibiotic properties.

  本发明涉及7.beta.-[D-2-氨基-2-(较低烷基磺酰胺基)-苯基]-乙酰氨基-3-R-头孢烯-4-羧酸及其盐，其中R代表原子序数高达35的较低烷氧基或卤素，这些化合物具有抗生素特性。
• Cephalosporin-derived inhibitors of β-Lactamase. Part 4: The C3 substituent
  作者：John D. Buynak、Lakshminarayana Vogeti、Venkata Ramana Doppalapudi、George Martin Solomon、Hansong Chen

  DOI：10.1016/s0960-894x(02)00205-6

  日期：2002.6

  New C3-substituted beta-lactamase inhibitors were prepared and evaluated against representative class A and class C enzymes. It was possible to improve simultaneous inhibitory activity of both classes of serine hydrolase. Other inhibitors showed high selectivity for either the class C cephalosporinases or the class A penicillinases. This represents the first time that cephalosporin-derived inhibitors have demonstrated selectivity for the class A beta-lactamases. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Lin, Ho-Shen; Rampersaud, Ashraff A.; Flokowitsch, Jane E., Journal of the Chinese Chemical Society, 1995, vol. 42, # 5, p. 833 - 846
  作者：Lin, Ho-Shen、Rampersaud, Ashraff A.、Flokowitsch, Jane E.、Alborn, William E.、Wu, Ernie C. Y.、Preston, David A.

  DOI：——

  日期：——