3-(Benzyloxy)-6-methylquinoline-2-carboxylic acid | 171917-59-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-(Benzyloxy)-6-methylquinoline-2-carboxylic acid
• 英文别名: 6-Methyl-3-phenylmethoxyquinoline-2-carboxylic acid
• CAS: 171917-59-2
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: GKADSVUAAMAKET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(Benzyloxy)-6-methylquinoline-2-carboxylic acid 在 palladium on activated charcoal 、 四丁基碘化铵 氢气 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 29.0h， 生成 3-Hydroxy-6-methyl-quinoline-2-carboxylic acid
  参考文献：
  名称：

  A Modified Friedlander Condensation for the Synthesis of 3-Hydroxyquinoline-2-carboxylates

  摘要：

  DOI：

  10.1021/jo00127a055
• 作为产物：
  描述：

  2-氨基-5-甲基苯甲醛 在 氢氧化钾 、 lithium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-(Benzyloxy)-6-methylquinoline-2-carboxylic acid
  参考文献：
  名称：

  Synthesis of key sandramycin analogs: systematic examination of the intercalation chromophore

  摘要：

  The preparation and examination of 2-22 constituting a systematic study of the chromophore of sandramycin (1) are detailed. Fluorescence quenching studies were used to establish binding constants for 1-24 within calf thymus DNA, within a single high affinity bis-intercalation binding site 5'-d(GCATGC)(2), and to establish the preference for sandramycin binding to 5'-d(GCXXGC)(2) where XX = AT, TA, GC, and CG. From the latter studies, sandramycin was found to exhibit a preference that follows the order: 5'-d(GCATGC)(2) > 5'-d(GCGCGC)(2), Delta Delta G degrees = 0.3 kcal/mol > 5'-d(GCTAGC)(2), 5'-d(GCCGGC)(2), Delta Delta G degrees = 0.6 kcal/mol although it binds with high affinity to all four deoxyoligonucleotides. The two highest affinity sequences constitute repeating 5'-PuPy motifs with each intercalation event occurring at a 5'-PyPu step. The most effective sequence constitutes the less stable duplex, contains the sterically most accessible minor groove central to the bis-intercalation site, and the ability to accept two gly-NH/T C2 carbonyl H-bonds identified in prior NMR studies. Similarly, the contribution of the individual structural features of the chromophore were assessed with the high affinity duplex sequence 5'-d(GCATGC)(2). To a first approximation, the cytotoxic properties were found to parallel trends established in the DNA binding affinities. The exception to this generalization was 4 which lacks the sandramycin chromophore phenol. Although typically 4-10x less potent than sandramycin against leukemia cell lines, it proved to be 1-10,000x more potent against melanomas, carcinomas, and adenocarcinomas exhibiting IC50 values of IpM-10 nM placing it among the most potent agents identified to date. Additionally, the first disclosure of the HIV-1 reverse transcriptase inhibitory activity of sandramycin (1) as well as that of its key analogs are described and define the chromophore structural features required for their exceptional potency. Two analogs, 18 and 3, roughly maintain the HIV-I reverse transcriptase inhibitory potency of 1 but exhibit substantially diminished cytotoxic activity (10(2) - 10(3)x). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(97)10014-1

文献信息

• SANDRAMYCIN ANALOGS
  申请人：The Scripps Research Institute

  公开号：EP0996458A1

  公开（公告）日：2000-05-03
• EP0996458A4
  申请人：——

  公开号：EP0996458A4

  公开（公告）日：2001-05-02
• US6329497B1
  申请人：——

  公开号：US6329497B1

  公开（公告）日：2001-12-11
• [EN] SANDRAMYCIN ANALOGS<br/>[FR] ANALOGUES DE SANDRAMYCINE
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：WO1998043663A1

  公开（公告）日：1998-10-08

  (EN) Analogs of sandramycin (1) are synthesized and shown to have cytoxic activity against various tumor cell types. The relative cytotoxic properties of the sandramycin analogs are approximately parallel to their relative DNA binding affinities. An exception to this generalization is compound (4) which completely lacks the sandramycin chromophore phenol. Although typically 4-10x less potent than sandramycin against leukemia cell lines, compound (4) proved to be 1-10,000x more potent against melanomas, carcinomas, and adenocarcinomas exhibiting IC50 values of 1 pM-10 nM. This activity places compound (4) among the most potent agents identified to date.(FR) Cette invention se rapporte à la synthèse d'analogues de sandramycine (1) qui s'avèrent présenter une activité cytotoxique dirigée contre divers types de cellules tumorales. Les propriétés cytotoxiques relatives de ces analogues de sandramycine sont sensiblement parallèles à leurs affinités relatives de liaison à l'ADN. Le composé (4), qui est totalement dépourvu de phénol chromophore de sandramycine constitue une exception à cette généralisation. Bien qu'il soit de 4 à 10 fois moins puissant que la sandramycine contre les lignées cellulaires de la leucémie, ce composé (4) s'est avéré être 1 à 10000 fois plus puissant contre les mélanomes, les carcinomes et les adénocarcinomes présentant des valeurs IC50 comprises entre 1 pM et 10 nM. Cette activité fait de ce composé (4) un des agents les plus puissants identifiés à ce jour.
• Synthesis of key sandramycin analogs: systematic examination of the intercalation chromophore
  作者：Dale L. Boger、Jyun-Hung Chen、Kurt W. Saionz、Qing Jin

  DOI：10.1016/s0968-0896(97)10014-1

  日期：1998.1

  The preparation and examination of 2-22 constituting a systematic study of the chromophore of sandramycin (1) are detailed. Fluorescence quenching studies were used to establish binding constants for 1-24 within calf thymus DNA, within a single high affinity bis-intercalation binding site 5'-d(GCATGC)(2), and to establish the preference for sandramycin binding to 5'-d(GCXXGC)(2) where XX = AT, TA, GC, and CG. From the latter studies, sandramycin was found to exhibit a preference that follows the order: 5'-d(GCATGC)(2) > 5'-d(GCGCGC)(2), Delta Delta G degrees = 0.3 kcal/mol > 5'-d(GCTAGC)(2), 5'-d(GCCGGC)(2), Delta Delta G degrees = 0.6 kcal/mol although it binds with high affinity to all four deoxyoligonucleotides. The two highest affinity sequences constitute repeating 5'-PuPy motifs with each intercalation event occurring at a 5'-PyPu step. The most effective sequence constitutes the less stable duplex, contains the sterically most accessible minor groove central to the bis-intercalation site, and the ability to accept two gly-NH/T C2 carbonyl H-bonds identified in prior NMR studies. Similarly, the contribution of the individual structural features of the chromophore were assessed with the high affinity duplex sequence 5'-d(GCATGC)(2). To a first approximation, the cytotoxic properties were found to parallel trends established in the DNA binding affinities. The exception to this generalization was 4 which lacks the sandramycin chromophore phenol. Although typically 4-10x less potent than sandramycin against leukemia cell lines, it proved to be 1-10,000x more potent against melanomas, carcinomas, and adenocarcinomas exhibiting IC50 values of IpM-10 nM placing it among the most potent agents identified to date. Additionally, the first disclosure of the HIV-1 reverse transcriptase inhibitory activity of sandramycin (1) as well as that of its key analogs are described and define the chromophore structural features required for their exceptional potency. Two analogs, 18 and 3, roughly maintain the HIV-I reverse transcriptase inhibitory potency of 1 but exhibit substantially diminished cytotoxic activity (10(2) - 10(3)x). (C) 1998 Elsevier Science Ltd. All rights reserved.