7-((3S,4S)-3-Amino-4-methoxy-pyrrolidin-1-yl)-4-oxo-1-thiazol-2-yl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-((3S,4S)-3-Amino-4-methoxy-pyrrolidin-1-yl)-4-oxo-1-thiazol-2-yl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
• 英文别名: 7-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylic acid
• 化学式: C₁₇H₁₇N₅O₄S
• 分子量: 387.419
• InChiKey: OCFVOHOLUYXSQZ-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  voreloxin中间体 在 盐酸 作用下， 以 乙腈 为溶剂， 生成 7-((3S,4S)-3-Amino-4-methoxy-pyrrolidin-1-yl)-4-oxo-1-thiazol-2-yl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 2

  摘要：

  We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyI derivative (271) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (SS)-isomer (AG-7352, 3) of 271, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.

  DOI：

  10.1021/jm0304966

文献信息

• COMPOUNDS AND COMPOSITIONS FOR TREATMENT OF CANCER
  申请人：Adelman Daniel C.

  公开号：US20100029708A1

  公开（公告）日：2010-02-04

  Compounds and compositions for treating, preventing or managing cancer are disclosed. The compositions provided herein comprise SNS-595 and N-desmethyl-SNS-595. Also provided are pharmaceutical compositions comprising the compounds and methods of treatment using the compounds and compositions.

  本文披露了用于治疗、预防或管理癌症的化合物和组合物。本文提供的组合物包括SNS-595和N-去甲基-SNS-595。还提供了含有这些化合物的药物组合物以及使用这些化合物和组合物的治疗方法。
• [EN] METHOD OF PREPARING (+)-1,4-DIHYDRO-7-[(3S,4S)-3METHOXY-4-(METHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ACIDE (+)-1,4-DIHYDRO-7-[(3S,4S)-3-MÉTHOXY-4-(MÉTHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTYRIDINE-3-CARBOXYLIQUE
  申请人：SUNESIS PHARMACEUTICAL INC

  公开号：WO2010078294A1

  公开（公告）日：2010-07-08

  Methods of preparing (+)-1, 4-dihydro-7-[(3S,45)-3-methoxy-4-(methylamino)-1 - pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid are disclosed. Also provided are pharmaceutical compositions comprising (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, and methods of treatment using such compositions.

  本发明揭示了制备(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的方法。本发明还提供了包含(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的药物组合物，并提供了使用这种组合物进行治疗的方法。
• Method of preparing (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid
  申请人：Sudhakar Anantha

  公开号：US20100203162A1

  公开（公告）日：2010-08-12

  Methods of preparing (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid are disclosed. Also provided are pharmaceutical compositions comprising (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, and methods of treatment using such compositions.

  本文披露了制备(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的方法。同时，还提供了含有(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的制药组合物，并且还提供了使用这种组合物进行治疗的方法。
• METHOD OF PREPARING (+)-1,4-DIHYDRO-7-[(3S,4S)-3-METHOXY-4-(METHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID
  申请人：Sunesis Pharmaceuticals, Inc.

  公开号：US20140171660A1

  公开（公告）日：2014-06-19

  Methods of preparing (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid are disclosed. Also provided are pharmaceutical compositions comprising (+)-1,4-dihydro-7-[(3S,45)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, and methods of treatment using such compositions.

  公开了制备(+)-1,4-二氢-7-[(3S,4S)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的方法。还提供了包含(+)-1,4-二氢-7-[(3S,45)-3-甲氧基-4-(甲基氨基)-1-吡咯烷基]-4-氧代-1-(2-噻唑基)-1,8-萘啶-3-羧酸的制药组合物，以及使用这种组合物进行治疗的方法。
• Compounds and compositions for treatment of cancer
  申请人：Sunesis Pharmaceuticals, Inc.

  公开号：EP2354138A1

  公开（公告）日：2011-08-10

  Compounds and compositions for treating, preventing or managing cancer are disclosed. The compositions provided herein comprise SNS-595 and N-desmethyl-SNS-595. Also provided are pharmaceutical compositions comprising the compounds and methods of treatment using the compounds and compositions.

  本研究公开了用于治疗、预防或控制癌症的化合物和组合物。本文提供的组合物包含 SNS-595 和 N-去甲基-SNS-595。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的治疗方法。