6-amino-5-chloro-2-methoxypyridine-3-carboxylic acid | 149539-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-amino-5-chloro-2-methoxypyridine-3-carboxylic acid
• 英文别名: 6-amino-5-chloro-2-methoxynicotinic acid；6-amino-5-chloro-2-(methyloxy)-3-pyridinecarboxylic acid
• CAS: 149539-83-3
• 化学式: C₇H₇ClN₂O₃
• 分子量: 202.597
• InChiKey: QKOVEUOBKSBZOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  85.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-amino-5-chloro-2-methoxypyridine-3-carboxylic acid 、 6-amino-1-ethyl-4-methylhexahydro-1,4-diazepine 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 6-Amino-5-chloro-N-(1-ethyl-4-methyl-[1,4]diazepan-6-yl)-2-methoxy-nicotinamide
  参考文献：
  名称：

  具有强效5-羟色胺5-HT3和多巴胺D2受体拮抗活性的新型N-（1-乙基-4-甲基六氢-1,4-二氮杂-6-基）吡啶-3-羧酰胺的合成与结构亲和关系。

  摘要：

  制备了由相应的苯甲酰胺5衍生的N-（1-乙基-4-甲基六氢-1,4-二氮杂-6-6-基）吡啶-3-甲酰胺的结构原始系列，并评估了其对多巴胺D（ 2）和分别使用大鼠纹状体和大鼠皮质膜的血清素5-HT（3）受体。许多合成的吡啶-3-羧酰胺对5-羟色胺5-HT（3）受体具有纳摩尔结合亲和力，对多巴胺D（2）受体具有中等至高结合亲和力。在吡啶环的5-位和6-位上分别引入更具亲脂性的溴原子和甲基氨基，增强了对多巴胺D（2）受体的亲和力，同时保持了强大的5-羟色胺5-HT（3）受体结合亲和力。由于结构相似性关系，选择5-溴-2-甲氧基-6-甲基氨基吡啶-3-羧酰胺53作为最有前途的产品，该产品对两种受体都具有高结合亲和力。化合物53对多巴胺D（2）和5-羟色胺5-HT（3）受体的亲和力比甲氧氯普胺（多巴胺D（2）受体； 23.3 nM对444 nM，5-羟色胺5-HT（3）受体的亲和力强得多。 0.97

  DOI：

  10.1021/jm020270n
• 作为产物：
  描述：

  6-氨基-2-甲氧基烟酸甲酯 在 sodium hydroxide 、 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-amino-5-chloro-2-methoxypyridine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)nicotinamides and their affinities for 5-HT3 and dopamine D2 receptors

  摘要：

  A series of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl) derivatives were prepared and evaluated for their binding to 5-HT3 and dopamine D-2 receptors. Among them, the 5-bromo-2-methoxy-6-methylaminonicotinamide 16 and its (R)-isomer were found to have potent affinities for both receptors. The affinities of(R)-16 for 5-HT3 and dopamine D-2 receptors are approximately 3-fold higher than those of the corresponding benzamide (R)-1 (IC50:1.1 and 12 nM vs. 2.9 and 35 nM, respectively). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00258-3

文献信息

• ２−アルコキシ−６−アミノ−５−ハロゲノ−Ｎ−（１−置換−４−ピペリジニル）ピリジン−３−カルボキサミド誘導体およびそれを含有する医薬組成物
  申请人：——

  公开号：JP2005082508A

  公开（公告）日：2005-03-31

  PROBLEM TO BE SOLVED: To provide a compound exhibiting high affinity for serotonin 4 receptor and useful as a digestive tract motion promoting agent or digestive tract function ameliorating agent.

  SOLUTION: The compound is represented by the formula(I), or an acid addition salt thereof and an intermediate thereof are provided. In formula(I), R1is a halogen atom; R2is H or a lower alkyl; R3is H, a lower alkyl or the like; R4is a lower alkyl; A is a group represented by the formula: Z-N(Q1)(Q2) or CO-R5, wherein Z is CO, CS or the like; Q1and Q2are each H, a lower alkyl or the like, or joined together with the nitrogen atom to which Q1and Q2are bound to form a pyrrolidine ring, piperidine ring or the like; and R5is H, a lower alkyl, lower alkoxy, lower alkoxycarbonyl or the like.

  COPYRIGHT: (C)2005,JPO&NCIPI

  要解决的问题是提供一种在5-羟色胺4受体具有高亲和力的化合物，可用作促进消化道蠕动或改善消化道功能的药剂。该化合物由以下公式(I)表示，或其酸盐和中间体提供。在公式(I)中，R1是卤原子；R2是H或较低的烷基；R3是H、较低的烷基或类似物；R4是较低的烷基；A是由以下公式表示的基团：Z-N(Q1)(Q2)或CO-R5，其中Z是CO、CS或类似物；Q1和Q2分别是H、较低的烷基或类似物，或与Q1和Q2连接的氮原子结合形成吡咯烷环、哌啶环或类似物；R5是H、较低的烷基、较低的烷氧基、较低的烷氧羰基或类似物。版权所有：(C)2005，JPO&NCIPI
• 5-HT.sub.4 antagonists
  申请人：SmithKline Beecham p.l.c.

  公开号：US05696129A1

  公开（公告）日：1997-12-09

  Compounds of formula (I), and pharmaceutically acceptable salts thereof, and the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in treatment of gastrointestinal disorders, cardiovasular disorders and CNS disorders.

  化合物的公式(I)及其药用盐，以及化合物的公式(I)或其药用盐在治疗胃肠道疾病、心血管疾病和中枢神经系统疾病中的用途。
• Oxo or oxy-pyridine compounds as 5-HT4 receptor modulators
  申请人：——

  公开号：US20030207875A1

  公开（公告）日：2003-11-06

  This invention provides compounds of the formula (I) and (II): 1 or the pharmaceutically acceptable esters thereof, and the pharmaceutically acceptable salts thereof: wherein R 1 is hydrogen or halo; R 2 and R 3 are independently hydrogen or C 1-6 alkyl; R 4 and R 5 are independently hydrogen or C 1-6 alkyl; R 6 is hydrogen, C 1-12 alkyl, C 1-6 alkoxy (C 1-6 )alkyl or C 1-12 alkyl substituted by up to 3 substituents selected from the groups consisting of C 3-8 cycloalkyl, aryl, heteroaryl and heterocyclic; R 7 and R 8 are hydrogen or taken together may form alkylene chain having one or two carbon atoms; R 9 is C 1-6 alkyl or C 3-8 cycloalkyl; R 10 is C 1-6 alkyl or NR 11 R 12 ; L is (CR 11 R 12 ) n or NR 11 ; M is NR 11 or (CR 11 R 12 ) n ; R 11 and R 12 are independently hydrogen or C 1-6 alkyl; n is an integer from 0 to 5; and m is an integer from 0 to 2; said heterocyclic, aryl and heteroaryl are unsubstituted or are substituted by at least one substituent selected from the group consisting of halo and C 1-6 alkyl; with the proviso that when R 9 is C 1-6 alkyl, L is not NR 11 . These compounds have 5-HT 4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.

  本发明提供了式(I)和(II)的化合物：1或其药学上可接受的酯和药学上可接受的盐：其中，R1是氢或卤素；R2和R3分别是氢或C1-6烷基；R4和R5分别是氢或C1-6烷基；R6是氢、C1-12烷基、C1-6烷氧基(C1-6)烷基或C1-12烷基，其被选自C3-8环烷基、芳基、杂芳基和杂环的最多3个取代基取代；R7和R8是氢或一起形成具有一个或两个碳原子的烷基链；R9是C1-6烷基或C3-8环烷基；R10是C1-6烷基或NR11R12；L是(CR11R12)或NR11；M是NR11或(CR11R12)n；R11和R12分别是氢或C1-6烷基；n是0到5的整数；m是0到2的整数；所述的杂环、芳基和杂芳基未取代或被至少一个取代基所取代，所述取代基被选自卤素和C1-6烷基；但当R9是C1-6烷基时，L不是NR11。这些化合物具有5-HT4受体结合活性，因此在哺乳动物，尤其是人类的治疗胃食管反流病、非溃疡性消化不良、肠易激综合征等方面是有用的。本发明还提供了包含上述化合物的制药组合物。
• PYRIDINE-3-CARBOXYLIC ACID ESTERS OR AMIDES USEFUL AS 5-HT 3? ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0611370A1

  公开（公告）日：1994-08-24
• 5-HT4 ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0662959A1

  公开（公告）日：1995-07-19