3-[(4-Fluorophenyl)sulfamoyl]-4-methylbenzoic acid | 379729-09-6

• 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: 3-[(4-Fluorophenyl)sulfamoyl]-4-methylbenzoic acid
• CAS: 379729-09-6
• 化学式: C₁₄H₁₂FNO₄S
• mdl: MFCD03152725
• 分子量: 309.318
• InChiKey: MTXSWENEFRJQMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[(4-Fluorophenyl)sulfamoyl]-4-methylbenzoic acid 在 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 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 2-azidoethyl (5-acetamido-9-(3-(4-fluoro-phenylsulfamoyl)-4-methylbenzoylamino)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  In Silico-Aided Design of a Glycan Ligand of Sialoadhesin for in Vivo Targeting of Macrophages

  摘要：

  Cell-specific delivery of therapeutic agents using ligand targeting is gaining interest because of its potential for increased efficacy and reduced side effects. The challenge is to develop a suitable ligand for a cell-surface receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn, Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed on subsets of resident and inflammatory macrophages, is an attractive target for the development of a ligand-targeted delivery system. Here we report the development of a high-affinity and selective ligancl for Sn that is an analogue of the natural ligand and is capable of targeting liposomal nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a library of similar to 8400 carboxylic acids was the key to identifying novel 9-N-acyl-substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead compounds. A small panel of targets were selected from the screen and synthesized to evaluate their affinities and selectivities. The most potent of these Sn ligands, (4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Ac alpha 2-3Gal beta 1-4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac liposomes were found to target liposomes selectively to cells expressing either murine or human Sn in vitro, and when administered to mice, they exhibited in vivo targeting to Sn-positive macrophages.

  DOI：

  10.1021/ja307501e
• 作为产物：
  描述：

  对甲基苯甲酸 在 氯磺酸 作用下， 以 乙腈 为溶剂， 反应 19.0h， 生成 3-[(4-Fluorophenyl)sulfamoyl]-4-methylbenzoic acid
  参考文献：
  名称：

  Synthesis, Characterization and Antimicrobial Activity of Bifunctional Sulfonamide-Amide Derivatives

  摘要：

  报道了一种方便的双功能磺胺酰胺衍生物的合成方法。首先通过4-甲基苯甲酸1的酰胺偶联反应，再与氯磺酸反应，生成乙基-4-（3-（氯磺酰基）-4-甲基苯甲酰基）哌嗪-1-羧酸酯4。所得化合物进一步与各种苯胺反应，生成目标磺胺酰胺衍生物5a-n。这些化合物的结构通过元素分析、红外光谱、$^1H$核磁共振、质谱以及从相应的4-甲基苯甲酸1和氯磺酸制备得到确认。所有这些新化合物均显示出显著的体外抗菌和抗真菌活性，对所有细菌和真菌株有效。

  DOI：

  10.5012/jkcs.2013.57.6.731

文献信息

• In Silico-Aided Design of a Glycan Ligand of Sialoadhesin for in Vivo Targeting of Macrophages
  作者：Corwin M. Nycholat、Christoph Rademacher、Norihito Kawasaki、James C. Paulson

  DOI：10.1021/ja307501e

  日期：2012.9.26

  Cell-specific delivery of therapeutic agents using ligand targeting is gaining interest because of its potential for increased efficacy and reduced side effects. The challenge is to develop a suitable ligand for a cell-surface receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn, Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed on subsets of resident and inflammatory macrophages, is an attractive target for the development of a ligand-targeted delivery system. Here we report the development of a high-affinity and selective ligancl for Sn that is an analogue of the natural ligand and is capable of targeting liposomal nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a library of similar to 8400 carboxylic acids was the key to identifying novel 9-N-acyl-substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead compounds. A small panel of targets were selected from the screen and synthesized to evaluate their affinities and selectivities. The most potent of these Sn ligands, (4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Ac alpha 2-3Gal beta 1-4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac liposomes were found to target liposomes selectively to cells expressing either murine or human Sn in vitro, and when administered to mice, they exhibited in vivo targeting to Sn-positive macrophages.
• Synthesis, Characterization and Antimicrobial Activity of Bifunctional Sulfonamide-Amide Derivatives
  作者：Babul Reddy A. Abbavaram、Hymavathi R.V. Reddyvari

  DOI：10.5012/jkcs.2013.57.6.731

  日期：2013.12.20

  A convenient synthesis of bifunctional sulfonamide-amide derivatives was reported. Amide coupling of 4-methyl benzoic acid 1 followed by reaction with chlorosulfonic acid produce ethyl-4-(3-(chlorosulfonyl)-4-methylbenzoyl)piperazine-1-carboxylate 4. The resulted compound on further treatment with various anilines produces the title sulfonamide-amide derivatives 5a-n. The configurations of these compounds were established by elemental analysis, IR, $^1H$ NMR, mass spectra, and by their preparation from the corresponding 4-methyl benzoic acid 1 and chlorosulfonic acid. All these new compounds demonstrate significant in vitro antibacterial and antifungal activities against all bacterial and fungal strains.

  报道了一种方便的双功能磺胺酰胺衍生物的合成方法。首先通过4-甲基苯甲酸1的酰胺偶联反应，再与氯磺酸反应，生成乙基-4-（3-（氯磺酰基）-4-甲基苯甲酰基）哌嗪-1-羧酸酯4。所得化合物进一步与各种苯胺反应，生成目标磺胺酰胺衍生物5a-n。这些化合物的结构通过元素分析、红外光谱、$^1H$核磁共振、质谱以及从相应的4-甲基苯甲酸1和氯磺酸制备得到确认。所有这些新化合物均显示出显著的体外抗菌和抗真菌活性，对所有细菌和真菌株有效。