(1R,5S,6S)-2-[(3S,5R)-5-[4-[N-(acetimidoyl)aminomethyl]phenyl]pyrrolidine-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride

• 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: (1R,5S,6S)-2-[(3S,5R)-5-[4-[N-(acetimidoyl)aminomethyl]phenyl]pyrrolidine-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride
• 英文别名: (1R,5S,6S)-2-[(3S,5R)-5-[4-[N-(acetimidoyl)aminomethyl]phenyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride；(1R,5S,6S)-2-[(3S,5R)-5-[4-(N-acetoimidoylaminomethyl)-phenyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride；(4R,5S,6S)-3-[(3S,5R)-5-[4-[(1-aminoethylideneamino)methyl]phenyl]pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid;hydrochloride
• 化学式: C₂₃H₃₀N₄O₄S*ClH
• 分子量: 495.043
• InChiKey: UGSWQNAIHBRXPD-GVZBVQCDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  154
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  杂氮双环磷酸酯 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 32.0h， 生成 (1R,5S,6S)-2-[(3S,5R)-5-[4-[N-(acetimidoyl)aminomethyl]phenyl]pyrrolidine-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  Structure–Activity Relationships of 1β-Methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems

  摘要：

  Structure-activity relationship studies of 1beta-methyl-2-[(3S,5R)-5-(4-aminomethylphenyl)pyrrolidin-3-ylthio]carbapenems, especially those pertaining to the relationship between antibacterial activity and side-chain structure were conducted. These studies suggested that the trans-(3S,5R)-5-phenylpyrrolidin-3-ylthio side-chain and the aminomethyl group at the 4-position of the phenyl ring play a key role in enhancing the antibacterial activity against the MRSA and Pseudomonas aeruginosa strains. In particular, the basicity of a substituent at the 4-position of the phenyl ring were shown to greatly contribute to the antibacterial activity against MRSA and methicillin-resistant Staphlyloccocus epidermidis strains. In contrast, the amidine group was shown to lead to potent antibacterial activity against P. aeruginosa strains comparable to that of imipenem, however, a good correlation between the basicity of the 4-substituent and antipseudomonal activity was not observed. In conclusion, the 4-aminomethyl or methylaminomethyl group on the phenyl ring was the best substituent for antipseudomonal activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00430-8

文献信息

• CARBAPENEM DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1048669A1

  公开（公告）日：2000-11-02

  Compounds represented by general formula (I); a process for producing the same; and utilization thereof as antimicrobial agents and metallo-β-lactamase inhibitors, wherein R1 represents hydrogen or lower alkyl; R2 represents hydrogen, an ester residue, etc.; R3 and R4 are the same or different and each represents hydrogen, halogeno, etc.; R5 and R6 are the same or different and each represents hydrogen, lower alkoxy, etc., or lower alkyl optionally having one or two substituents selected from the group consisting of carbamoyl, carboxy and hydroxy; group (a) represents aryl selected from the group consisting of benzene and naphthalene rings, etc.; and Y represents a single bond, linear C1-4 alkylene, etc. (provided that the case where R3 and R4 are hydrogen, (a) is benzene, Y is methylene and R5 and R6 are hydrogen is excluded).

  化合物的一般式（I）；其制备方法；以及作为抗微生物剂和金属β-内酰胺酶抑制剂的应用，其中R1代表氢或较低的烷基；R2代表氢、酯基残基等；R3和R4相同或不同，每个代表氢、卤素等；R5和R6相同或不同，每个代表氢、较低的烷氧基等，或较低的烷基可选地具有羰基、羧基和羟基中的一种或两种取代基；组（a）代表苯环和萘环等中选择的芳基；Y代表单键，线性C1-4烷基等（前提是当R3和R4为氢，（a）为苯环，Y为亚甲基，R5和R6为氢时，不包括在内）。