4-(3,5-difluorobenzyloxy)benzene-1-sulfonyl chloride

• 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: 4-(3,5-difluorobenzyloxy)benzene-1-sulfonyl chloride
• 英文别名: 4-(3,5-difluro-benzyloxy)-benzenesulfonyl chloride；4-[(3,5-Difluorobenzyl)oxy]benzenesulfonyl chloride；4-[(3,5-difluorophenyl)methoxy]benzenesulfonyl chloride
• 化学式: C₁₃H₉ClF₂O₃S
• 分子量: 318.728
• InChiKey: XJNFPYMRYTXREJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3,5-difluorobenzyloxy)benzene-1-sulfonyl chloride 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 2-(4-(3,5-difluorobenzyloxy)phenylsulfonamido)-N-hydroxyacetamide
  参考文献：
  名称：

  Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models

  摘要：

  Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nivi on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.

  DOI：

  10.1021/jm4011753
• 作为产物：
  描述：

  sodium p-hydroxybenzenesulfonate 在 草酰氯 、 sodium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 48.0h， 生成 4-(3,5-difluorobenzyloxy)benzene-1-sulfonyl chloride
  参考文献：
  名称：

  Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models

  摘要：

  Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nivi on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.

  DOI：

  10.1021/jm4011753

文献信息

• TACE INHIBITORS
  申请人：——

  公开号：US20030181441A1

  公开（公告）日：2003-09-25

  A compound of the formula 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Q are as defined above, useful in the treatment of arthritis, cancer, and other diseases involving the dysregulated production/release of reprolysins such as TNF and other diseases characterized by matrix metalloproteinase activity. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID's), COX-2 inhibitors and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.

  一种具有以下式1的化合物，其中R1、R2、R3、R4、R5、R6和Q的定义如上所述，在治疗关节炎、癌症和其他涉及重组蛋白酶素（如TNF）异常产生/释放的疾病，以及其他以基质金属蛋白酶酶活性为特征的疾病中有用。此外，本发明的化合物可与标准非甾体类抗炎药（NSAID）、COX-2抑制剂和镇痛药联合治疗，也可与顺铂、多柔比星、顺铂、依托泊苷、紫杉醇、多西他素等细胞毒药物联合使用，用于癌症治疗。
• TACE inhibitors
  申请人：McClure F. Kim

  公开号：US20050215549A1

  公开（公告）日：2005-09-29

  A compound of the formula wherein R 1 , R 2 R 3 , R 4 , R 5 , R 6 and Q are as defined above, useful in the treatment of arthritis, cancer, and other diseases involving the dysregulated production/release of reprolysins such as TNF and other diseases characterized by matrix metalloproteinase activity. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID's), COX-2 inhibitors and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.

  该化合物的化学式为其中R1，R2，R3，R4，R5，R6和Q如上定义，可用于治疗关节炎、癌症和其他涉及重复蛋白酶（如TNF）的失调生产/释放以及其他以基质金属蛋白酶活性为特征的疾病。此外，本发明的化合物可与标准非甾体抗炎药（NSAID's）、COX-2抑制剂和镇痛药一起用于联合治疗，并与顺铂、多柔比星、顺铂、依托泊苷、紫杉醇、多西他赛和其他生物碱（如长春碱）一起用于癌症治疗。
• WEATHER-RESISTANT COMPOSITION, COATING MATERIALS AND MOLDED ARTICLES
  申请人：OTSUKA CHEMICAL COMPANY, LIMITED

  公开号：EP1104790A1

  公开（公告）日：2001-06-06

  The present invention relates to a weather-resistant composition comprising a bisbenzotriazolylphenol compound represented by the general formula (1): [wherein A represents an alkylene group, and R1 and R2 represent a group (B): (in which R3 and R4 represent an alkyl group)], a (meth)acrylate compound, and a curing agent; a coating material containing the weather-resistant composition as a main component; and a molded article. The composition can form a coating film which is not impaired in mechanical strength, exhibits excellent weather resistance, metal ion resistance and transparency for a prolonged period, and is less likely to cause surface cracks.

  本发明涉及一种耐候性组合物，该组合物包含通式（1）所代表的双苯并三唑酚化合物： [其中 A 代表亚烷基，R1 和 R2 代表基团 (B)： (其中 R3 和 R4 代表烷基）]、(甲基)丙烯酸酯化合物和固化剂；含有该耐候性组合物作为主要成分的涂层材料；以及成型制品。该组合物可形成一层涂膜，该涂膜的机械强度不受损害，具有出色的耐候性、耐金属离子性和长时间的透明度，并且不易产生表面裂纹。
• Synthesis and biological activity of piperazine-Based dual MMP-13 and TNF-α converting enzyme inhibitors
  作者：Michael A. Letavic、John T. Barberia、Thomas J. Carty、Joel R. Hardink、Jennifer Liras、Lori L. Lopresti-Morrow、Peter G. Mitchell、Mark C. Noe、Lisa M. Reeves、Sheri L. Snow、Ethan J. Stam、Francis J. Sweeney、Marcie L. Vaughn、Chul H. Yu

  DOI：10.1016/s0960-894x(03)00666-8

  日期：2003.10

  A series of novel MMP-13 and TNF-alpha converting enzyme inhibitors based on piperazine 2-hydroxamic acid scaffolds are described. The TACE, MMP-1 and MMP-13 activity of these inhibitors as well as the effect of substitution of the piperazine nitro-en and the P-1' benzyloxy tailpiece is discussed. Moderate in vivo activity is observed with several members of this group. (C) 2003 Elsevier Ltd. All rights reserved.
• [EN] TACE INHIBITORS<br/>[FR] INHIBITEURS DE L'ENZYME DE CONVERSION DU FACTEUR DE NECROSE TUMORALE ALPHA (TACE)
  申请人：PFIZER PROD INC

  公开号：WO2000009492A1

  公开（公告）日：2000-02-24

  A compound of formula (I), wherein R?1, R2, R3, R4, R5, R6¿ and Q are as defined, useful in the treatment of arthritis, cancer, and other diseases involving the dysregulated production/release of reprolysins such as TNF and other diseases characterized by matrix metalloproteinase activity. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NASAIDs), COX-2 inhibitors and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.