7-甲基-8-喹啉羧酸 | 70585-54-5

• 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
• 中文名称: 7-甲基-8-喹啉羧酸
• 中文别名: 7-甲基喹啉-8-甲酸
• 英文名称: (7-methyl)quinoline-8-carboxylic acid
• 英文别名: 7-methyl-8-quinolinecarboxylic acid；7-methylquinoline-8-carboxylic Acid
• CAS: 70585-54-5
• 化学式: C₁₁H₉NO₂
• 分子量: 187.198
• InChiKey: YESWBAYAPYBVQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  7-甲基-8-喹啉羧酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 7-Methyl-quinoline-8-carboxylic acid (4-trifluoromethyl-phenyl)-amide
  参考文献：
  名称：

  Aromatic Quinolinecarboxamides as Selective, Orally Active Antibody Production Inhibitors for Prevention of Acute Xenograft Rejection

  摘要：

  The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed not only fail to discriminate between B- and T-cells but also have a narrow therapeutic window and, thus, their prolonged use in complex immunosuppressive regimens is problematic. By capitalizing on the target enzyme-bound (DHODH) structure Ib of one of these compounds, leflunomide, and modulating part of its multiple mechanisms of action to gain selectivity, the quinoline-8-carboxamide 3 was designed as a potentially weak enzyme inhibitor but effective immunosuppressant. Compound 3 fulfilled the mechanistic criteria set and had 10-fold B-cell over T-cell selectivity. Its pyridyl analogue 4 was found to be a highly potent and selective B-cell immunosuppressant with a 75-fold selectivity for B- over T-cells las judged by the MLR data) and no general cytotoxicity at concentrations up to 160-fold higher than those required to inhibit B-cells. In the mouse, 4 effectively blocked TI-1 Ab production and suppressed Ab-mediated xenograft rejection in a xenotransplantation model under a once-daily dosing regimen, with efficacy down to 0.3 mg/kg/day po. These are the first data demonstrating the feasibility of the development of drugs specific for impeding Ah production.

  DOI：

  10.1021/jm010822m
• 作为产物：
  描述：

  2-氨基-6-甲基苯甲酸 、 丙烯醛 以 邻二氯苯 为溶剂， 反应 3.0h， 以12%的产率得到7-甲基-8-喹啉羧酸
  参考文献：
  名称：

  Aromatic Quinolinecarboxamides as Selective, Orally Active Antibody Production Inhibitors for Prevention of Acute Xenograft Rejection

  摘要：

  The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed not only fail to discriminate between B- and T-cells but also have a narrow therapeutic window and, thus, their prolonged use in complex immunosuppressive regimens is problematic. By capitalizing on the target enzyme-bound (DHODH) structure Ib of one of these compounds, leflunomide, and modulating part of its multiple mechanisms of action to gain selectivity, the quinoline-8-carboxamide 3 was designed as a potentially weak enzyme inhibitor but effective immunosuppressant. Compound 3 fulfilled the mechanistic criteria set and had 10-fold B-cell over T-cell selectivity. Its pyridyl analogue 4 was found to be a highly potent and selective B-cell immunosuppressant with a 75-fold selectivity for B- over T-cells las judged by the MLR data) and no general cytotoxicity at concentrations up to 160-fold higher than those required to inhibit B-cells. In the mouse, 4 effectively blocked TI-1 Ab production and suppressed Ab-mediated xenograft rejection in a xenotransplantation model under a once-daily dosing regimen, with efficacy down to 0.3 mg/kg/day po. These are the first data demonstrating the feasibility of the development of drugs specific for impeding Ah production.

  DOI：

  10.1021/jm010822m

文献信息

• Catalytic Formation of Ketones from Unactivated Esters through Rhodium Chelation-Assisted C–O Bond Activation
  作者：Jingjing Wang、Sujing Zuo、Weiqiang Chen、Xinrui Zhang、Kaixin Tan、Yun Tian、Jianhui Wang

  DOI：10.1021/jo400949p

  日期：2013.9.6

  A new method for building aryl aryl ketones containing heterocyclic rings through chelation-assisted C–O bond activation catalyzed by a rhodium complex has been developed. In this reaction, methyl quinoline-8-carboxylate, methyl quinoxaline-5-carboxylate, and their derivatives were reacted with an excess amount of a substituted phenyl boronic acid in the presence of a rhodium(I) complex to give substituted

  开发了一种新的方法，该方法通过铑配合物催化的螯合辅助C–O键活化来构建含杂环的芳基芳基酮。在该反应中，在铑（I）络合物的存在下，使喹啉8-羧酸甲酯，喹喔啉-5-羧酸甲酯及其衍生物与过量的取代的苯基硼酸反应，得到取代的苯基（喹啉-中高收率的8-基）甲酮，苯基喹喔啉-5-基甲酮及其衍生物。当前的方法提供了非常有利的合成途径，以有效地构建具有8-苯甲酰基喹啉核心结构的相关药物。这种方法对于药物化学家来说可能是特别有价值的，因为它可以将多功能酮部分后期引入复杂的支架中，从而实现面向多样性的合成策略。
• 8-(1H-Tetrazol-5-yl-carbamoyl)quinoline compounds
  申请人：Riker Laboratories, Inc.

  公开号：US04147694A1

  公开（公告）日：1979-04-03

  8-(1H-Tetrazol-5-ylcarbamoyl)quinolines and pharmaceutically acceptable salts thereof are potent anti-allergic agents.

  (1H-四唑-5-基甲酰)喹啉及其药用盐是有效的抗过敏药物。
• Methods of using 8(tetrazol-5-ylcarbamoyl)isoquinoline compounds
  申请人：Riker Laboratories, Inc.

  公开号：US04186201A1

  公开（公告）日：1980-01-29

  8-(1H-Tetrazol-5-ylcarbamoyl)quinolines and pharmaceutically acceptable salts thereof are potent anti-allergic agents.

  (8-1H-四唑-5-基氨甲酰)喹啉及其药学上可接受的盐是强效的抗过敏药物。
• US4147694A
  申请人：——

  公开号：US4147694A

  公开（公告）日：1979-04-03
• US4186201A
  申请人：——

  公开号：US4186201A

  公开（公告）日：1980-01-29