N-(2-((4-tert-butylphenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-N-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(2-((4-tert-butylphenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-N-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide
• 英文别名: N-[2-(4-tert-butylanilino)-1-(4-methoxyphenyl)-2-oxoethyl]-N-methyl-6-oxo-1H-pyridine-3-carboxamide
• 化学式: C₂₆H₂₉N₃O₄
• 分子量: 447.534
• InChiKey: PIBUURJIMMZKSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-甲氧基苯硼酸 在 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 17.0h， 生成 N-(2-((4-tert-butylphenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-N-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of orally efficacious RORγt inverse agonists, part 1: Identification of novel phenylglycinamides as lead scaffolds

  摘要：

  A series of novel phenylglycinamides as retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) inverse agonists were discovered through optimization of a high-throughput screen hit 1. (R)-N-(2-((3,5-Difluoro-4-(trimethylsilyl)phenyl) amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methylisoxazole-5-carboxamide (22) was identified as one of the best of these compounds. It displayed higher subtype selectivity and specificity over other nuclear receptors and demonstrated in vivo potency to suppress the transcriptional activity of ROR gamma t in a mouse PD (pharmacodynamic) model upon oral administration. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.12.006

文献信息

• Discovery of orally efficacious RORγt inverse agonists, part 1: Identification of novel phenylglycinamides as lead scaffolds
  作者：Junya Shirai、Yoshihide Tomata、Mitsunori Kono、Atsuko Ochida、Yoshiyuki Fukase、Ayumu Sato、Shinichi Masada、Tetsuji Kawamoto、Kazuko Yonemori、Ryoukichi Koyama、Hideyuki Nakagawa、Masaharu Nakayama、Keiko Uga、Akira Shibata、Keiko Koga、Toshitake Okui、Mikio Shirasaki、Robert Skene、BiChing Sang、Isaac Hoffman、Wes Lane、Yasushi Fujitani、Masashi Yamasaki、Satoshi Yamamoto

  DOI：10.1016/j.bmc.2017.12.006

  日期：2018.1

  A series of novel phenylglycinamides as retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) inverse agonists were discovered through optimization of a high-throughput screen hit 1. (R)-N-(2-((3,5-Difluoro-4-(trimethylsilyl)phenyl) amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methylisoxazole-5-carboxamide (22) was identified as one of the best of these compounds. It displayed higher subtype selectivity and specificity over other nuclear receptors and demonstrated in vivo potency to suppress the transcriptional activity of ROR gamma t in a mouse PD (pharmacodynamic) model upon oral administration. (C) 2017 Elsevier Ltd. All rights reserved.