isopropyl 3-((N-(2-methoxy-2-oxoethyl)-4-methylphenylsulfonamido)methyl)picolinate | 412334-35-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: isopropyl 3-((N-(2-methoxy-2-oxoethyl)-4-methylphenylsulfonamido)methyl)picolinate
• 英文别名: 3-{[methoxycarbonylmethyl-(toluene-4-sulfonyl)-amino]-methyl}-pyridine-2-carboxylic acid isopropyl ester；propan-2-yl 3-[[(2-methoxy-2-oxoethyl)-(4-methylphenyl)sulfonylamino]methyl]pyridine-2-carboxylate
• CAS: 412334-35-1
• 化学式: C₂₀H₂₄N₂O₆S
• 分子量: 420.486
• InChiKey: PNMJLJGBBPMRSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  isopropyl 3-((N-(2-methoxy-2-oxoethyl)-4-methylphenylsulfonamido)methyl)picolinate 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 24.0h， 生成 N-(4-fluorobenzyl)-8-hydroxy-5-bromo-1,6-naphthyridine-7-carboxamide
  参考文献：
  名称：

  Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties

  摘要：

  Among a large number of HIV-1 integrase (IN) inhibitors, the 8-hydroxy-[1,6]naphthyridines (i.e., L-870,810) were one of the promising class of antiretroviral drugs developed by Merck Laboratories. In spite of its remarkable potency and efficacy, unfortunately upon completion of phase I clinical studies, development of L-870,810 was halted. Because of its desirable pharmacological and pharmaceutical properties we were intrigued to design novel analogues of L-870,810 with goals to (1) improve upon limitations of naphthyridine-7-carboxamides as antiviral agents and (2) to reposition their use as innovative cytotoxic agents for cancer therapeutics. Herein, we report on the design and synthesis of a series of 1,6-naphthyridine-7-carboxamides with various substitutions at the 5- and 8-positions. All the new 5-substituted-8-hydroxy-[1,6]naphthyridines were potent IN inhibitors and the 5-substituted-8-amino-[1,6]naphthyridines were significantly cytotoxic. Further optimization of the 5,8-disubstituted-[1,6]naphthyridines with structural variation on 7-carboxamide delivered novel compounds with significant cytotoxicity in a panel of cancer cell lines and effective inhibition against select oncogenic kinases.

  DOI：

  10.1021/jm300667v
• 作为产物：
  描述：

  2,3-吡啶二羧酸酐 在 sodium tetrahydroborate 、 氯化亚砜 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 生成 isopropyl 3-((N-(2-methoxy-2-oxoethyl)-4-methylphenylsulfonamido)methyl)picolinate
  参考文献：
  名称：

  三取代咪唑并二氮杂萘酮化合物及其制备方 法和用途

  摘要：

  本发明涉及通式I所示的1,3,5‑三取代‑1H‑咪唑并[4,5‑h]1,6‑二氮杂萘‑2(3H)‑酮化合物、其异构体及药学上可接受的盐，其制备方法和用途以及包含所述化合物的组合物。本发明还涉及所述化合物、其异构体及药学上可接受的盐及含有其的组合物作为多靶点蛋白激酶抑制剂在制备用于治疗肿瘤疾病等与蛋白激酶特别是c‑Met有关的疾病的药物中的用途。

  公开号：

  CN103709162B

文献信息

• Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors
  申请人：——

  公开号：US20030055071A1

  公开（公告）日：2003-03-20

  Aza- and polyaza-naphthalenyl carboxamide derivatives including certain quinoline carboxamide and naphthyridine carboxamide derivatives are described. These compounds are inhibitors of HIV integrase and inhibitors of HIV replication, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

  描述了包括某些喹啉羧酰胺和萘啉羧酰胺衍生物在内的氮杂萘基羧酰胺衍生物。这些化合物是HIV整合酶的抑制剂和HIV复制的抑制剂，可用于预防或治疗HIV感染和治疗艾滋病，作为化合物或药学上可接受的盐，或作为药物组合物中的成分，可选择与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。还描述了预防、治疗或延缓艾滋病发作的方法，以及预防或治疗HIV感染的方法。
• Chemo-selective Suzuki–Miyaura reactions: Synthesis of highly substituted [1,6]-naphthyridines
  作者：Yadavalli Suneel Kumar、Fazlur-Rahman Nawaz Khan

  DOI：10.1016/j.cclet.2017.02.007

  日期：2017.7

  The Suzuki-Miyaura reaction of methyl-5-bromo-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate (5), with 2 equiv. of arylboronic acids gave diarylated product, 5,8–diaryl-1,6-naphthyridine-7-carboxylate (7), whereas 1 equiv. of arylboronic acid resulted in site-selective formation of 5-aryl-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate (8). The reactions proceeded with excellent chemo-selectivity in favor

  5-溴8-（甲苯磺酰氧基）-1,6-萘啶-7-羧酸甲酯（5）的Suzuki-Miyaura反应（2）。芳基硼酸的合成给出了二芳基化产物5,8-二芳基-1,6-萘啶-7-羧酸盐（7），而当量为1当量。芳基硼酸的过量导致5-芳基-8-（甲苯磺酰氧基）-1，6-萘啶-7-羧酸盐的位点选择性形成（8）。该反应以优异的化学选择性进行，有利于溴化物基团。同样，通过顺序添加与完全不同的硼酸进行一锅法反应，生成1，6-萘啶-7-羧酸盐（10），在5和8位含有两个不同的芳基。
• Aza-and polyaza-naphthalenyl-carboxamides useful as hiv integrase inhibitors
  申请人：——

  公开号：US20040034221A1

  公开（公告）日：2004-02-19

  Aza- and polyaza-naphthalenyl carboxamide derivatives including certain quinoline carboxamide and naphthyridine carboxamide derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

  本文描述了包括某些喹啉羧酰胺和萘啶羧酰胺衍生物在内的Aza-和polyaza-萘啶基羧酰胺衍生物，作为HIV整合酶的抑制剂和HIV复制的抑制剂。这些化合物作为化合物或药物可接受的盐，或作为制药组合物中的成分，可用于预防或治疗HIV感染和治疗艾滋病，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。本文还描述了预防、治疗或延迟艾滋病发作的方法以及预防或治疗HIV感染的方法。
• Aza-and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors
  申请人：——

  公开号：US20040044207A1

  公开（公告）日：2004-03-04

  Aza- and polyaza-naphthalenyl carboxamide derivatives including certain quinoline carboxamide and naphthyridine carboxamide derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating, or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

  本文描述了包括某些喹啉羧酰胺和萘啶羧酰胺衍生物在内的Aza-和polyaza-萘基羧酰胺衍生物，作为HIV整合酶的抑制剂和HIV复制的抑制剂。这些化合物可作为化合物或药物可接受的盐，或作为药物组成部分，可选与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用，用于预防或治疗HIV感染和治疗艾滋病。还描述了预防、治疗或延迟艾滋病发作的方法以及预防或治疗HIV感染的方法。
• Process for preparing 5-sulfonamido-8-hydroxy-1,6-naphthyridine-7-carboxamides
  申请人：Maligres E. Peter

  公开号：US20050014780A1

  公开（公告）日：2005-01-20

  The preparation of 5-sulfonamido-8-hydroxy-1,6-naphthyridine-7-carboxamides is disclosed. A 5-halo-8-hydroxy-1,6-napthyridine-7-carboxylic acid or acid ester in which the hydroxy is derivatized with a protecting group is reacted with a sulfonamide (e.g., an alkanesulfonamide, N-alkyl alkanesulfonamide, or alkanesultam) in the presence of a copper promoter and a chelating agent, followed by deprotection of the hydroxy group, and then coupling with an amine to obtain the 5-sulfonamido-8-hydroxy-1,6-naphthyridine-7-carboxamide. Alternatively, the hydroxy-protected 5-halo-8-hydroxy-1,6-napthyridine-7-carboxylic acid (or ester) is first coupled with an amine, the resulting carboxamide reacted with a sulfonamide followed by deprotection of the hydroxy group to obtain the 5-sulfonamido-8-hydroxy-1,6-naphthyridine-7-carboxamide. The 5-sulfonamido-8-hydroxy-1,6-naphthyridine-7-carboxamides are inhibitors of HIV integrase and are useful for treating HIV infection, preventing HIV infection, delaying the onset of AIDS, and treating AIDS.

  本文公开了制备5-磺酰胺基-8-羟基-1,6-萘啶-7-羧酸酰胺的方法。首先将5-卤代-8-羟基-1,6-萘啶-7-羧酸或酸酯与保护羟基的衍生物反应，加入磺酰胺（例如，烷基磺酰胺，N-烷基磺酰胺或烷基磺酰胺）和铜催化剂以及螯合剂，去除保护羟基，然后与胺偶联，得到5-磺酰胺基-8-羟基-1,6-萘啶-7-羧酸酰胺。或者，先将保护羟基的5-卤代-8-羟基-1,6-萘啶-7-羧酸（或酯）与胺偶联，然后将产生的羧酰胺与磺酰胺反应，去除保护羟基，得到5-磺酰胺基-8-羟基-1,6-萘啶-7-羧酸酰胺。5-磺酰胺基-8-羟基-1,6-萘啶-7-羧酸酰胺是HIV整合酶的抑制剂，可用于治疗HIV感染，预防HIV感染，延缓艾滋病的发作和治疗艾滋病。