methyl 4,5-diamino-2-methylbenzofuran-7-carboxylate | 1374298-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: methyl 4,5-diamino-2-methylbenzofuran-7-carboxylate
• 英文别名: methyl 4,5-diamino-2-methyl-1-benzofuran-7-carboxylate；Methyl 4,5-diamino-2-methyl-7-benzofurancarboxylate
• CAS: 1374298-24-4
• 化学式: C₁₁H₁₂N₂O₃
• 分子量: 220.228
• InChiKey: HJYZGGAIJIGGLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  91.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4,5-diamino-2-methylbenzofuran-7-carboxylate 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 sodium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 24.0h， 生成 2-((2-chloro-6-fluorophenyl)amino)-N-(cyclohexylmethyl)-7-methyl-1H-benzofuro[4,5-d]imidazole-5-carboxamide
  参考文献：
  名称：

  Discovery of furan and dihydrofuran-fused tricyclic benzo[ d ]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1

  摘要：

  This letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mPGES-1 inhibitors, capable of inhibiting an increased PGE(2) production in the disease state. Structure-activity optimization afforded many potent mPGES-1 inhibitors having <50 nM potencies in the A549 cellular assay and adequate metabolic stability in liver microsomes. Lead compounds 8l and 8m demonstrated reasonable in vitro pharmacology and pharmacokinetic properties over other compounds. In particular, 8m revealed satisfactory oral pharmacokinetics and bioavailability in multiple species like rat, guinea pig, dog and cynomolgus monkey. In addition, the representative compound 8m showed in vivo efficacy by inhibiting LPS-induced thermal hyperalgesia with an ED50 of 14.3 mg/kg in guinea pig. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.10.062
• 作为产物：
  描述：

  methyl 4-amino-5-nitro-2-(prop-2-yn-1-yloxy)benzoate 在 盐酸 、 铁粉 、 cesium fluoride 作用下， 以 水 为溶剂， 反应 24.0h， 生成 methyl 4,5-diamino-2-methylbenzofuran-7-carboxylate
  参考文献：
  名称：

  Discovery of furan and dihydrofuran-fused tricyclic benzo[ d ]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1

  摘要：

  This letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mPGES-1 inhibitors, capable of inhibiting an increased PGE(2) production in the disease state. Structure-activity optimization afforded many potent mPGES-1 inhibitors having <50 nM potencies in the A549 cellular assay and adequate metabolic stability in liver microsomes. Lead compounds 8l and 8m demonstrated reasonable in vitro pharmacology and pharmacokinetic properties over other compounds. In particular, 8m revealed satisfactory oral pharmacokinetics and bioavailability in multiple species like rat, guinea pig, dog and cynomolgus monkey. In addition, the representative compound 8m showed in vivo efficacy by inhibiting LPS-induced thermal hyperalgesia with an ED50 of 14.3 mg/kg in guinea pig. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.10.062

文献信息

• Tricyclic Compounds As mPGES-1 Inhibitors
  申请人：Gharat Laxmikant A.

  公开号：US20120108583A1

  公开（公告）日：2012-05-03

  The present invention relates to tricyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.

  本发明涉及式(I)的三环化合物或其药用可接受的盐作为mPGES-1抑制剂。这些化合物是微粒体前列腺素E合成酶-1（mPGES-1）酶的抑制剂，因此在治疗各种疾病或病况引起的疼痛和/或炎症方面具有用处，如哮喘、骨关节炎、类风湿性关节炎、急性或慢性疼痛和神经退行性疾病。
• US8519149B2
  申请人：——

  公开号：US8519149B2

  公开（公告）日：2013-08-27
• [EN] TRICYCLIC COMPOUNDS AS MPGES-1 INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES EN TANT QU'INHIBITEURS DE MPGES-1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2012055995A1

  公开（公告）日：2012-05-03

  The present invention relates to tricyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.