2-(4-benzamido-2-oxopyridin-1(2H)-yl)-N-benzyl-4-methylthiazole-5-carboxamide | 1105690-21-8

• 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-(4-benzamido-2-oxopyridin-1(2H)-yl)-N-benzyl-4-methylthiazole-5-carboxamide
• 英文别名: 2-(4-benzamido-2-oxopyridin-1-yl)-N-benzyl-4-methyl-1,3-thiazole-5-carboxamide
• CAS: 1105690-21-8
• 化学式: C₂₄H₂₀N₄O₃S
• 分子量: 444.514
• InChiKey: HQBAPTGULWUDNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-溴-4-甲基噻唑-5-羧酸 在 吡啶 、 copper(l) iodide 、 8-羟基喹啉 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-benzamido-2-oxopyridin-1(2H)-yl)-N-benzyl-4-methylthiazole-5-carboxamide
  参考文献：
  名称：

  Discovery of thiazolylpyridinone SCD1 inhibitors with preferential liver distribution and reduced mechanism-based adverse effects

  摘要：

  We discovered a series of novel and potent thiazolylpyridinone-based SCD1 inhibitors based on a 2-aminothiazole HTS hit by replacing the amide bond with a pyridinone moiety. Compound 19 demonstrated good potency against SCD1 in vitro and in vivo. The mouse liver microsomal SCD1 in vitro potency for 19 was improved by more than 240-fold compared to the original HTS hit. Furthermore, 19 demonstrated a dose-dependent reduction of plasma desaturation index with an ED50 of 6.3 mg/kg. Compound 19 demonstrated high liver to plasma and liver to eyelid exposures, indicating preferential liver distribution. The preliminary toxicology study with compound 19 did not demonstrate adverse effects related to SCD1 inhibition, suggesting a wide safety margin with respect to other known SCD1 inhibitors with wider distribution profiles. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.035

文献信息

• ORGANIC COMPOUNDS
  申请人：Dales Natalie

  公开号：US20090156615A1

  公开（公告）日：2009-06-18

  The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了调节硬脂酰辅酶A去饱和酶活性的杂环衍生物。还涵盖了利用这些衍生物调节硬脂酰辅酶A去饱和酶活性的方法以及包含这些衍生物的药物组合物。
• Organic compounds
  申请人：Dales Natalie

  公开号：US08501746B2

  公开（公告）日：2013-08-06

  The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.

  本发明提供了可以调节硬脂酰辅酶A去饱和酶活性的杂环衍生物。本发明还包括使用这些衍生物来调节硬脂酰辅酶A去饱和酶活性的方法和包含这些衍生物的药物组合物。
• US8501746B2
  申请人：——

  公开号：US8501746B2

  公开（公告）日：2013-08-06
• Discovery of thiazolylpyridinone SCD1 inhibitors with preferential liver distribution and reduced mechanism-based adverse effects
  作者：Shaoyi Sun、Zaihui Zhang、Vandna Raina、Natalia Pokrovskaia、Duanjie Hou、Rostam Namdari、Kuldip Khakh、Leslie G. Ratkay、David G. McLaren、Monica Mork、Jianmin Fu、Suzie Ferreira、Brian Hubbard、Michael D. Winther、Natalie Dales

  DOI：10.1016/j.bmcl.2013.12.035

  日期：2014.1

  We discovered a series of novel and potent thiazolylpyridinone-based SCD1 inhibitors based on a 2-aminothiazole HTS hit by replacing the amide bond with a pyridinone moiety. Compound 19 demonstrated good potency against SCD1 in vitro and in vivo. The mouse liver microsomal SCD1 in vitro potency for 19 was improved by more than 240-fold compared to the original HTS hit. Furthermore, 19 demonstrated a dose-dependent reduction of plasma desaturation index with an ED50 of 6.3 mg/kg. Compound 19 demonstrated high liver to plasma and liver to eyelid exposures, indicating preferential liver distribution. The preliminary toxicology study with compound 19 did not demonstrate adverse effects related to SCD1 inhibition, suggesting a wide safety margin with respect to other known SCD1 inhibitors with wider distribution profiles. (C) 2013 Elsevier Ltd. All rights reserved.