2-(6-fluoro-2-(4-methylpicolinoyl)-1H-indol-3-yl)acetic acid | 231294-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(6-fluoro-2-(4-methylpicolinoyl)-1H-indol-3-yl)acetic acid
• 英文别名: [6-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid；2-[6-fluoro-2-(4-methylpyridine-2-carbonyl)-1H-indol-3-yl]acetic acid
• CAS: 231294-86-3
• 化学式: C₁₇H₁₃FN₂O₃
• 分子量: 312.3
• InChiKey: SZQLJRUPQGEKLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  83
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氟-1-碘-2-硝基苯 在 吡啶 、 palladium diacetate 、 铁粉 、 potassium carbonate 、 氯化铵 、 三乙胺 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 99.5h， 生成 2-(6-fluoro-2-(4-methylpicolinoyl)-1H-indol-3-yl)acetic acid
  参考文献：
  名称：

  Novel acid-type cyclooxygenase-2 inhibitors: Design, synthesis, and structure–activity relationship for anti-inflammatory drug

  摘要：

  Cyclooxygenase (COX) is a key rate-limiting enzyme for prostaglandin (PG) production cascades in the human body. The mechanisms of both the anti-inflammation effects and the side-effects of traditional COX inhibitors are associated with the existence of two COX isoforms. Thus while COX-1 is predominantly expressed ubiquitously and constitutively, and it serves a housekeeping role in processes such as gastrointestinal (GI) mucosa protection, COX-2 is absent or exhibits a low level of expression in most tissues, and is highly upregulated in response to endotoxin, virus, inflammatory or tissue-injury stimuli/signals, and tumour promoter in the various types of organs, tissues, and cells. Furthermore, COX-2 contribution to PGE(2) and PGI(2) production evokes and sustains systemic or peripheral inflammatory disease, but it is not involved in the COX-1-mediated GI tract events. Also, hypersensitivity of aspirin owing to its inhibitory action against COX-1 is a significant concern clinically. Consequently, highly selective COX-2 inhibitors have been needed for the treatment of inflammatory- and inflammation related-diseases that include pyrexia, inflammation, pain, rheumatoid arthritis, osteoarthritis, and cancers. In this study, a series of novel [2-{[(4-substituted or 4,5-disubstituted)-pyridin-2-yl]carbonyl}-(5- or 6-substituted or 5,6-disubstituted)-1H-indol-3-yl]acetic acid analogues was designed, synthesized, and evaluated to identify potent and selective COX-2 inhibitors as potential agents against inflammatory diseases. As significant findings, the present study clarified unique structure activity relationship of the analogues toward potent and selective COX-2 inhibition in vitro, and identified 2-{6-fluoro-2-[4-methyl-2-pridinyl)carbonyl]-1H-indol-3-yl}acetic acid as a potent and selective COX-2 inhibitor in vitro that demonstrated orally potent anti-inflammation efficacy against carrageenan-induced oedema formation in the foot of SPF/VAF male SD rats as a peripheral inflammation model in vivo. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.053

文献信息

• [EN] 2,3-SUBSTITUTED INDOLE COMPOUNDS AS COX-2 INHIBITORS<br/>[FR] COMPOSES INDOLE 2,3-SUBSTITUES UTILISES COMME INHIBITEURS DE COX-2
  申请人：PFIZER PHARMACEUTICALS INC.

  公开号：WO1999035130A1

  公开（公告）日：1999-07-15

  (EN) This invention provides a compound of formula (I) or the pharmaceutically acceptable salts thereof wherein Z is OH, C1-6 alkoxy, -NR2R3 or heterocycle; Q is selected from the following: (a) an optionally substituted phenyl, (b) an optionally substituted 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), (c) an optionally substituted 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, (d) an optionally substituted C3-7 cycloalkyl and (e) an optionally substituted benzofuzed heterocycle; R1 is hydrogen, C1-4 alkyl or halo; R2 and R3 are independently hydrogen, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy or CN; X is independently selected from H, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino and CN; and n is 0, 1, 2, 3 and 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.(FR) Cette invention porte sur un composé de la formule (I) ou sur les sels pharmaceutiquement acceptables de celui-ci, formule dans laquelle Z représente OH, alcoxy C1-6, -NR2R3 ou un hétérocycle; Q est sélectionné parmi: (a) un phényle éventuellement substitué, (b) un groupe aromatique monocyclique à 6 éléments éventuellement substitué contenant un, deux, trois ou quatre atomes d'azote, (c) un groupe aromatique monocyclique à 5 éléments éventuellement substitué contenant un hétéroatome sélectionné parmi O, S et N et contenant éventuellement un, deux ou trois atomes d'azote en plus de l'hétéroatome, (d) un cycloalkyle C3-7 éventuellement substitué et (e) un hétérocycle fusionné à benzo éventuellement substitué; R1 représente hydrogène, alkyle C1-4 ou halo; R2 et R3 représentent, indépendamment, hydrogène, OH, alcoxy C1-4, alkyle C1-4 ou alkyle C1-4 substitué par halo, OH, alcoxy C1-4 ou CN; X est indépendamment sélectionné parmi H, halo, alkyle C1-4, alkyle C1-4 halo-substitué, OH, alcoxy C1-4, alcoxy C1-4 halo-substitué, alkylthio C1-4, NO2, NH2, di-(C1-4alkyl)amino et CN; et n vaut 0, 1, 2, 3 et 4. Cette invention porte également sur une composition pharmaceutique utilisée dans le traitement d'un état pathologique dans lequel les prostaglandines sont impliquées comme agents pathogènes.

  该发明提供了式（I）的化合物或其药学上可接受的盐，其中Z代表OH，C1-6烷氧基，-NR2R3或杂环；Q从以下选取：（a）可选取取代苯基，（b）可选取含有一个、两个、三个或四个氮原子的6元单环芳香基，（c）可选取含有O、S和N中选取的一个杂原子的可选取取代的5元单环芳香基，并且除了所述杂原子外，还可含有一个、两个或三个氮原子，（d）可选取可选取取代的C3-7环烷基和（e）可选取取代的苯并杂环；R1代表氢、C1-4烷基或卤素；R2和R3独立地代表氢、OH、C1-4烷氧基、C1-4烷基或C1-4烷基取代的卤素、OH、C1-4烷氧基或CN；X独立地从H、卤素、C1-4烷基、卤素取代的C1-4烷基、OH、C1-4烷氧基、卤素取代的C1-4烷氧基、C1-4烷基硫、NO2、NH2、双（C1-4烷基）氨基和CN中选取；n为0、1、2、3和4。该发明还提供了一种药物组合物，用于治疗前列腺素作为病原体所涉及的医疗状况。
• 5HT1 receptor agonists and a cox-2 inhibitor or NSAID for the treatment of migraine
  申请人：Pfizer Products Inc.

  公开号：EP1051995A2

  公开（公告）日：2000-11-15

  The present invention relates to a method of treating migraine in a mammal, including a human, by administering to the mammal a 5HT1 receptor agonist in combination with a cyclooxygenase-2 (COX-2) inhibitor. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a 5HT1 receptor agonist with a cyclooxygenase-2 (COX-2) inhibitor.

  本发明涉及一种治疗哺乳动物（包括人类）偏头痛的方法，其方法是向哺乳动物施用 5HT1 受体激动剂与环氧合酶-2 (COX-2) 抑制剂。本发明还涉及含有药学上可接受的载体、5HT1 受体激动剂和环氧化酶-2 (COX-2) 抑制剂的药物组合物。
• Combination of an 5HT1 receptor antagonist, caffeine and a cyclooxygenase-2 inhibitor for the treatment of migraine
  申请人：Pfizer Products Inc.

  公开号：EP1064966A2

  公开（公告）日：2001-01-03

  The present invention relates to a method of treating migraine in a mammal, including a human, by administering to the mammal a 5HT1 receptor agonist in combination with caffeine and a cyclooxygenase-2 (COX-2) inhibitor. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a 5HT1 receptor agonist with caffeine and a cyclooxygenase-2 (COX-2) inhibitor.

  本发明涉及一种治疗哺乳动物（包括人类）偏头痛的方法，其方法是向哺乳动物施用5HT1受体激动剂与咖啡因和环氧化酶-2（COX-2）抑制剂。它还涉及含有药学上可接受的载体、5HT1受体激动剂与咖啡因和环氧化酶-2 (COX-2)抑制剂的药物组合物。
• Combinations of aldose reductase inhibitors and selective cyclooxygenase-2 inhibitors
  申请人：Pfizer Products Inc.

  公开号：EP1064965A2

  公开（公告）日：2001-01-03

  This invention is directed to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and a selective COX-2 inhibitor,a prodrug thereof or a pharmaceutically acceptable salt of said selective COX-2 inhibitor or said prodrug. This invention further relates to methods of using those pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy and diabetic cardiomyopathy.

  本发明涉及包含醛糖还原酶抑制剂（ARI）、其原药或所述ARI或所述原药的药学上可接受的盐和选择性COX-2抑制剂、其原药或所述选择性COX-2抑制剂或所述原药的药学上可接受的盐的方法、药物组合物和试剂盒。本发明进一步涉及使用这些药物组合物治疗糖尿病并发症如糖尿病神经病变、糖尿病肾病变、糖尿病视网膜病变和糖尿病心肌病变的方法。
• 2,3-SUBSTITUTED INDOLE COMPOUNDS AS COX-2 INHIBITORS
  申请人：PFIZER INC.

  公开号：EP1045833A1

  公开（公告）日：2000-10-25