2-chloro-5-(isobutyramidomethyl)-4-methylbenzoic acid | 1381846-29-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-5-(isobutyramidomethyl)-4-methylbenzoic acid
• 英文别名: 2-chloro-4-methyl-5-[(2-methylpropanoylamino)methyl]benzoic acid；2-Chloro-4-methyl-5-[(2-methylpropanoylamino)methyl]benzoic acid
• CAS: 1381846-29-2
• 化学式: C₁₃H₁₆ClNO₃
• 分子量: 269.728
• InChiKey: CENWKGMPLDRPQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-5-(isobutyramidomethyl)-4-methylbenzoic acid 、 2-氨基咪唑硫酸盐 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以61%的产率得到N-(1H-imidazol-2-yl)-2-chloro-4-methyl-5-(isobutyramidomethyl)benzamide
  参考文献：
  名称：

  Novel Imidazole-2-Benzamide Compounds Useful for the Treatment of Osteoarthritis

  摘要：

  本发明提供了下面公式的化合物或其药用盐，其中R1、R2和R3如本文所述；使用这些化合物治疗骨关节炎的方法；以及制备这些化合物的方法。

  公开号：

  US20120157506A1
• 作为产物：
  描述：

  N-(hydroxymethyl)-2-methylpropanamide 、 2-氯-4-甲基苯甲酸 在 硫酸 作用下， 以21%的产率得到2-chloro-5-(isobutyramidomethyl)-4-methylbenzoic acid
  参考文献：
  名称：

  Discovery and Characterization of 2-Acylaminoimidazole Microsomal Prostaglandin E Synthase-1 Inhibitors

  摘要：

  As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 mu M. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate substituent alleviated time-dependent cytochrome P450 3A4 (CYP3A4) inhibition. Further structure-activity relationship (SAR) studies led to 8, which had desirable potency (IC50 = 12 nM in an ex vivo human whole blood (HWB) assay) and absorption, distribution, metabolism, and excretion (ADME) properties. Studies on the formulation of 8 identified 8 center dot H3PO4 as suitable for clinical development. Omission of a lipophilic portion of the compound led to 26, a readily orally bioavailable inhibitor with potency in HWB comparable to celecoxib. Furthermore, 26 was selective for mPGES-1 inhibition versus other mechanisms in the prostanoid pathway. These factors led to the selection of 26 as a second clinical candidate.

  DOI：

  10.1021/acs.jmedchem.5b01249

文献信息

• Novel Imidazole-2-Benzamide Compounds Useful for the Treatment of Osteoarthritis
  申请人：Kuklish Steven Lee

  公开号：US20120157506A1

  公开（公告）日：2012-06-21

  The present invention provides compounds of the formula below or pharmaceutical salts thereof, wherein R1, R2 and R3 are as described herein; methods of treating osteoarthritis using the compounds; and a process for preparing the compounds.

  本发明提供了下面公式的化合物或其药用盐，其中R1、R2和R3如本文所述；使用这些化合物治疗骨关节炎的方法；以及制备这些化合物的方法。
• Imidazole-2-benzamide compounds useful for the treatment of osteoarthritis
  申请人：Eli Lilly and Company

  公开号：US08252831B2

  公开（公告）日：2012-08-28

  The present invention provides compounds of the formula below or pharmaceutical salts thereof, wherein R1, R2 and R3 are as described herein; methods of treating osteoarthritis using the compounds; and a process for preparing the compounds.

  本发明提供以下公式的化合物或其药物盐，其中R1、R2和R3如本文所述；使用这些化合物治疗骨关节炎的方法；以及制备这些化合物的过程。
• NOVEL IMIDAZOLE-2-BENZAMIDE COMPOUNDS USEFUL FOR THE TREATMENT OF OSTEOARTHRITIS
  申请人：Eli Lilly and Company

  公开号：EP2655335A1

  公开（公告）日：2013-10-30
• US8252831B2
  申请人：——

  公开号：US8252831B2

  公开（公告）日：2012-08-28
• [EN] NOVEL IMIDAZOLE-2-BENZAMIDE COMPOUNDS USEFUL FOR THE TREATMENT OF OSTEOARTHRITIS<br/>[FR] NOUVEAUX COMPOSÉS D'IMIDAZOLE-2-BENZAMIDE UTILES POUR TRAITEMENT DE L'ARTHROSE
  申请人：LILLY CO ELI

  公开号：WO2012087771A1

  公开（公告）日：2012-06-28

  The present invention provides compounds of the formula (I) below or pharmaceutical salts thereof, wherein R1, R2 and R3 are as described herein; methods of treating osteoarthritis using the compounds; and a process for preparing the compounds.