(2R,4R)-2-[4-(N-allyloxycarbonyl-N-methylaminomethyl)phenyl]-1-allyloxycarbonyl-4-hydroxypyrrolidine | 228267-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2R,4R)-2-[4-(N-allyloxycarbonyl-N-methylaminomethyl)phenyl]-1-allyloxycarbonyl-4-hydroxypyrrolidine
• 英文别名: (2 R ,4 R)-1-allyloxycarbonyl-4-hydroxy-2-[4-(N-allyloxycarbonyl-N-methylaminomethyl)-phenyl]pyrrolidine；prop-2-enyl (2R,4R)-4-hydroxy-2-[4-[[methyl(prop-2-enoxycarbonyl)amino]methyl]phenyl]pyrrolidine-1-carboxylate
• CAS: 228267-25-2
• 化学式: C₂₀H₂₆N₂O₅
• 分子量: 374.437
• InChiKey: KJUJVJSBQNQSBL-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  79.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,4R)-2-[4-(N-allyloxycarbonyl-N-methylaminomethyl)phenyl]-1-allyloxycarbonyl-4-hydroxypyrrolidine 在 bis-triphenylphosphine-palladium(II) chloride sodium hydroxide 、 三正丁基氢锡 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-2-[(3S,5R)-5-(4-(N-methylaminomethyl)phenyl)pyrrolidin-3-ylthio]-1-carbapen-2-em-3-carboxylic acid
  参考文献：
  名称：

  A Novel 1.BETA.-Methylcarbapenem, J-111,225: Effects of the C-3 and C-5 Stereochemistry of the Pyrrolidinylthio Side Chain on Antibacterial Activities.

  摘要：

  DOI：

  10.7164/antibiotics.53.314
• 作为产物：
  描述：

  (2R,4R)-1-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-(4-formylphenyl)pyrrolidine 在 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 1.5h， 生成 (2R,4R)-2-[4-(N-allyloxycarbonyl-N-methylaminomethyl)phenyl]-1-allyloxycarbonyl-4-hydroxypyrrolidine
  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

• [EN] BI-PYRROLIDINYLVINL (CARBA) CEPHALOSPORINS<br/>[FR] BI-PYRROLIDINYLVINYL (CARBA) CEPHALOSPORINES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2000032605A1

  公开（公告）日：2000-06-08

  The present invention relates to cephalosporin derivatives of general formula (I), wherein R is R4 -Ys-(CR5R6)m- or (formula a) R1, R2 are each independently hydrogen or lower alkyl; R3 is hydrogen, hydroxy-lower alkyl or carbamoylmethyl; Z is phenylene, heterocyclylen or naphthylene; R4 is halogen, phenyl, benzyl, naphthyl or heterocyclyl, the phenyl, benzyl, naphthyl or heterocyclyl being optionally substituted by at least one of halogen, hydroxy, optionally substituted lower alkyl, lower alkoxy, amino, lower alkylamino, di-lower alkylamino, carboxy, lower alkoxycarbonyl or carbamoyl; Q is S or CH¿2?; Y is S, O, NH or CH2; M is 0 or 1; s is 0 or 1; R?5, R6¿ are each independently hydrogen or lower alkyl; X is CR8 or N; R7 is hydrogen, lower alkyl, lower cycloalkyl, formyl, acetyl or pivaloyl; R8 is hydrogen or halogen; and readily hydrolyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula (I) and of their esters and salts. The invention is further concerned with the manufacture of compounds of formula (I); with their use as pharmaceutically active substances, particularly for the treatment and prophylaxis of infectious diseases, and with pharmaceutical preparations containing a compound of formula (I) for the treatment and prophylaxis of infectious diseases.
• Structure–Activity Relationships of 1β-Methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems
  作者：Hiroki Sato、Hiroki Sakoh、Takashi Hashihayata、Hideaki Imamura、Norikazu Ohtake、Aya Shimizu、Yuichi Sugimoto、Shunji Sakuraba、Rie Bamba-Nagano、Koji Yamada、Terutaka Hashizume、Hajime Morishima

  DOI：10.1016/s0968-0896(01)00430-8

  日期：2002.5

  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.
• A Novel 1.BETA.-Methylcarbapenem, J-111,225: Effects of the C-3 and C-5 Stereochemistry of the Pyrrolidinylthio Side Chain on Antibacterial Activities.
  作者：HIDEAKI IMAMURA、AYA SHIMIZU、HIROKI SATO、YUICHI SUGIMOTO、SHUNJI SAKURABA、RIE NAGANO、KOJI YAMADA、TERUTAKA HASHIZUME、HAJIME MORISHIMA

  DOI：10.7164/antibiotics.53.314

  日期：——