N-(3-(3,5-dimethylphenylamino)-8-nitro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzenesulfonamide | 1301627-28-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(3-(3,5-dimethylphenylamino)-8-nitro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzenesulfonamide
• 英文别名: N-(3-((3,5-dimethylphenyl)amino)-8-nitro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzenesulphonamide；N-[3-(3,5-dimethylanilino)-8-nitro-1,4-dioxonaphthalen-2-yl]benzenesulfonamide
• CAS: 1301627-28-0
• 化学式: C₂₄H₁₉N₃O₆S
• 分子量: 477.497
• InChiKey: KETGPIPAOWUXRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(3-(3,5-dimethylphenylamino)-8-nitro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzenesulfonamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以100%的产率得到N-(8-amino-3-(3,5-dimethylphenylamino)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzenesulfonamide
  参考文献：
  名称：

  Structure–activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1

  摘要：

  A naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pK(a), inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.03.015
• 作为产物：
  描述：

  2,3-二氯-5-硝基-1,4-萘醌 在 cerium(III) chloride heptahydrate 、 caesium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 N-(3-(3,5-dimethylphenylamino)-8-nitro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzenesulfonamide
  参考文献：
  名称：

  Structure–activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1

  摘要：

  A naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pK(a), inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.03.015

文献信息

• [EN] 1,4-QUINONES AND THEIR SULFUR ANALOGUES USEFUL AS LIGANDS OF N-ACETYLTRANSFERASES<br/>[FR] 1,4-QUINONES ET LEURS ANALOGUES SOUFRÉS UTILES EN TANT QUE LIGANDS DE N-ACÉTYLTRANSFÉRASES
  申请人：ISIS INNOVATION

  公开号：WO2011055142A3

  公开（公告）日：2011-08-11
• Structure–activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1
  作者：James E. Egleton、Cyrille C. Thinnes、Peter T. Seden、Nicola Laurieri、Siu Po Lee、Kate S. Hadavizadeh、Angelina R. Measures、Alan M. Jones、Sam Thompson、Amy Varney、Graham M. Wynne、Ali Ryan、Edith Sim、Angela J. Russell

  DOI：10.1016/j.bmc.2014.03.015

  日期：2014.6

  A naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pK(a), inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors. (C) 2014 Published by Elsevier Ltd.