(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-[(1-tert-butoxycarbonyl-1-methylethoxy)imino]acetyl chloride hydrochloride | 116856-00-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-[(1-tert-butoxycarbonyl-1-methylethoxy)imino]acetyl chloride hydrochloride
• 英文别名: (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetyl chloride hydrochloride；tert-butyl 2-[(Z)-[1-(5-amino-1,2,4-thiadiazol-4-ium-3-yl)-2-chloro-2-oxoethylidene]amino]oxy-2-methylpropanoate;chloride
• CAS: 116856-00-9
• 化学式: C₁₂H₁₇ClN₄O₄S*ClH
• 分子量: 385.271
• InChiKey: KHWQNZUGDVDKEA-FPUQOWELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.15
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-[(1-tert-butoxycarbonyl-1-methylethoxy)imino]acetyl chloride hydrochloride 、 7β-amino-3-[3-formamido-4-(formamidomethyl)-2-methyl-1-pyrazolio]methyl-3-cephem-4-carboxylate bis(trifluoroacetate) 在 N-三甲基硅基乙酰胺 、 苯甲醚 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-formamido-4-(formamidomethyl)-2-methyl-1-pyrazolio]methyl-3-cephem-4-carboxylate bis(trifluoroacetate)
  参考文献：
  名称：

  Structural requirements for the stability of novel cephalosporins to AmpC β-lactamase based on 3D-structure

  摘要：

  AmpC beta-lactamase is one of the leading causes of Pseudomonas aeruginosa (P. aeruginosa) resistance to cephalosporins. FR259647 is a cephalosporin having a novel pyrazolium substituent at the 3-position and exhibits excellent activity (MIC = 1 mu g/mL) against the AmpC beta-lactamase overproducing P. aeruginosa FP1380 strain in comparison with the third-generation cephalosporins FK518 [Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 454; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 455; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 456; Abstracts of Papers, 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, GA, October 21-24, 1990, Abs. 457] (MIC = 16 mu g/mL) and ceftazidime (CAZ) (MIC = 128 mu g/mL). The stability of FR259647 and FK518 to AmpC beta-lactamase was evaluated using MIC assays against both the P. aeruginosa PAO1 strain and a PAO1 mutant strain overproducing AmpC beta-lactamase as a differential assay, which indicates that the main difference derives from their stability to AmpC beta-lactamase. A structural analysis using computer simulations indicated that the difference in stability may be due to steric hindrance of the 3-position substituents causing differential affinity. This steric hindrance may disturb entry of the cephalosporins into the binding pocket. We predicted the possibility of inhibition of entry as a potential means of enhancing stability by conformational analysis. In order to validate this speculation, novel FR259647 derivatives 4-9 were designed, calculated, synthesized, and evaluated. As a result, we demonstrated that their probability of entry correlated with the MIC ratio of the mutant strain to the parent strain and supports the validity of our model. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.074
• 作为产物：
  描述：

  头孢唑兰侧链酸活性硫酯 在 五氯化磷 作用下， 以 二氯甲烷 、 异丙醚 为溶剂， 生成 (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-[(1-tert-butoxycarbonyl-1-methylethoxy)imino]acetyl chloride hydrochloride
  参考文献：
  名称：

  Cephem compounds and processes for preparation thereof

  摘要：

  制备了7.β.-[2-5氨基-1，2，4-噻二唑-3-基)2(羧基较低烷氧基亚氨基)乙酰胺]-3-(3-氨基-2-烷基-1-吡唑啉)甲基3头孢烯4羧酸盐。它们是抗生素。

  公开号：

  US04927818A1

文献信息

• Cephem compounds and processes for preparation thereof
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04927818A1

  公开（公告）日：1990-05-22

  7 .beta.-[2-5 amino-1, 2, 4 thiadiazol-3yl) 2(carboxy lower alkyleneoxyimino) acetamido]-3-(3-amino-2-alkyl-1-pyrazolio) methyl 3 cephem 4 carboxylates are prepared. They are antibiotics.

  制备了7.β.-[2-5氨基-1，2，4-噻二唑-3-基)2(羧基较低烷氧基亚氨基)乙酰胺]-3-(3-氨基-2-烷基-1-吡唑啉)甲基3头孢烯4羧酸盐。它们是抗生素。
• Intermediates for cephem compounds
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05162520A1

  公开（公告）日：1992-11-10

  The invention relates to intermediate compounds of the formula: ##STR1## wherein R.sup.3 is a lower alkyl, hydroxy(lower)alkyl or a protected hydroxy(lower)alkyl, R.sup.4 is amino or a protected amino group, and R.sup.5 is hydrogen or lower alkyl, or a salt thereof, useful in the preparation of compounds of antimicrobial activity.

  本发明涉及式为：##STR1##的中间化合物，其中R.sup.3是较低的烷基，羟基（较低）烷基或保护羟基（较低）烷基，R.sup.4是氨基或保护氨基团，R.sup.5是氢或较低的烷基，或其盐，在制备抗微生物活性化合物方面有用。
• Cephem compounds
  申请人：——

  公开号：US20040248875A1

  公开（公告）日：2004-12-09

  The present invention relates to a compound of the formula [I]: wherein A is lower alkylene or lower alkenylene; R1 is lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl or protected amino(lower)alkyl, and R2 is hydrogen or amino protecting group, or R1 and R2 are bonded together and form lower alkylene; R3 and R5 are independently amino or protected amino; and R4 is carboxy or protected carboxy, 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. 1

  本发明涉及一种化合物，其化学式为[I]：其中，A为较低的烷基或烯基烷基；R1为较低的烷基、羟基(较低)烷基、保护羟基(较低)烷基、氨基(较低)烷基或保护氨基(较低)烷基，R2为氢或氨基保护基，或R1和R2结合形成较低的烷基；R3和R5独立地为氨基或保护氨基；R4为羧基或保护羧基，或其药学上可接受的盐，以及制备化学式[I]的化合物的方法和包含化学式[I]的化合物与药学上可接受的载体混合的制药组合物。
• Cephem compounds, processes for preparation thereof and pharmaceutical compositions comprising them
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0261615A2

  公开（公告）日：1988-03-30

  A compound of the formula : wherein R1 and R4 are each amino or a protected amino group, R2 is carboxy(lower)alkyl or a protected carboxy(lower)alky], R3 is lower alkyl, hydroxy(lower)alkyl or a protected hydroxy(lower)alkyl, and R5 is hydrogen or lower alkyl, and a pharmaceutically acceptable salt thereof, processes for their preparation and pharmaceutical compositions comprising them as an active ingredient. The invention further relates to intermediate compounds of the formula and their preparation.

  式中的化合物： 其中 R1 和 R4 分别为氨基或受保护的氨基、 R2 是羧基（低级）烷基或受保护的羧基（低级）烷基、］ R3 是低级烷基、羟基（低级）烷基或受保护的羟基（低级）烷基，以及 R5 是氢或低级烷基、 及其药学上可接受的盐、它们的制备工艺和含有它们作为活性成分的药物组合物。本发明进一步涉及式 及其制备方法。
• CEPHEM COMPOUNDS
  申请人：Astellas Pharma Inc.

  公开号：EP1392704B1

  公开（公告）日：2006-02-22