N-(3-bromopropyl)-4-(fluorosulfonyl)benzamide | 321907-05-5

• 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: N-(3-bromopropyl)-4-(fluorosulfonyl)benzamide
• 英文别名: 4-(3-Bromopropylcarbamoyl)benzenesulfonyl fluoride
• CAS: 321907-05-5
• 化学式: C₁₀H₁₁BrFNO₃S
• 分子量: 324.171
• InChiKey: HMOGITLSLZSUCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-bromopropyl)-4-(fluorosulfonyl)benzamide 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 4-[3-(8-Cyclopentyl-2,6-dioxo-1-propyl-1,2,6,7-tetrahydro-purin-3-yl)-propylcarbamoyl]-benzenesulfonyl fluoride
  参考文献：
  名称：

  Fluorosulfonyl-Substituted Xanthines as Selective Irreversible Antagonists for the A₁-Adenosine Receptor

  摘要：

  FSCPX (1) has been reported to be a potent, selective, and irreversible antagonist for the A(1)-adenosine receptor (AR). To obtain an irreversible A(1)AR antagonist with potentially better stability and to further elucidate the effects of linker structure on the pharmacological characteristics, several new analogues were targeted in which the labile ester linkage of 1 was replaced by more stable functionalities. In particular, alkyl and:amide linkers between the xanthine pharmacophore and the reactive 4-fluorosulfonylphenyl group were explored. The data showed that the chemical composition of the linker affects the affinity and apparent irreversible binding to the A(1)AR. Overall, compound 23b appeared to have the most advantageous characteristics as a potential irreversible ligand for the A(1)AR. These include relatively high affinity for the A(1)AR. as compared to the A(2A)AR, concentration-dependent and selective apparent irreversible binding to the A(1)AR, and ease;of removal of unbound ligand from biological membranes. These :properties indicate that 23b has the potential to be a useful tool for further study of the structure and function of the A(1)AR.

  DOI：

  10.1021/jm000181f
• 作为产物：
  描述：

  4-(氯磺酰)苯甲酸 在 potassium hydrogen difluoride 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 1,3-二噁烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(3-bromopropyl)-4-(fluorosulfonyl)benzamide
  参考文献：
  名称：

  A Chemical Biological Approach to Study G Protein-Coupled Receptors: Labeling the Adenosine A₁ Receptor Using an Electrophilic Covalent Probe

  摘要：

  DOI：

  10.1021/acschembio.2c00589

文献信息

• Design and pharmacological profile of a novel covalent partial agonist for the adenosine A1 receptor
  作者：Xue Yang、Majlen A. Dilweg、Dion Osemwengie、Lindsey Burggraaff、Daan van der Es、Laura H. Heitman、Adriaan P. IJzerman

  DOI：10.1016/j.bcp.2020.114144

  日期：2020.10

  Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A1 receptor (hA1AR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. Accordingly, the design and profiling of novel hA1AR partial agonists has become an

  与完全激动剂相比，G蛋白偶联受体（GPCR）的部分激动剂为新型药物治疗提供了机会，具有更高的靶标安全性。对于人类腺苷A1受体（hA1AR），这导致了Capadenoson的发现，该药物已进入IIa期用于心力衰竭的临床试验。因此，新型hA1AR部分激动剂的设计和分析已成为重要的研究重点。在这项研究中，我们报告LUF7746，一种带有亲电性氟磺酰基部分的卡帕德森衍生物，作为不可逆结合的hA1AR调节剂。同时，在我们的研究中，设计了带有甲基磺酰基部分的非反应性配体LUF7747作为对照探针。在放射性配体结合试验中，LUF7746的表观亲和力随着预孵育时间的延长而增加到纳摩尔范围，提示共价结合水平随时间增加。此外，与参考的完全激动剂CPA相比，LUF7746在hA1AR介导的G蛋白活化分析中是部分激动剂，并且对拮抗剂/反向激动剂的阻滞具有抵抗力。基于计算机结构的对接研究与hA1AR的定点诱变相结合，证明氨基酸Y2717
• 10.1002/cbic.202400242
  作者：Payne, China M.、Baltos, Jo-Anne、Langiu, Monica、Sinh Lu, Cam、Tyndall, Joel D. A.、Gregory, Karen J.、May, Lauren T.、Vernall, Andrea J.

  DOI：10.1002/cbic.202400242

  日期：——

  Bivalent dicovalent compounds for the adenosine A1 receptor. We developed a series of bivalent compounds whereby each side contains the same ligand and covalent warhead. We show these compounds could be interacting across the adenosine A1 homodimer and have improved adenosine receptor subtype selectivity compared to the single covalent ligand counterpart.

  腺苷 A1 受体的二价二共价化合物。我们开发了一系列二价化合物，其中每侧都包含相同的配体和共价弹头。我们发现这些化合物可以跨腺苷 A1 同型二聚体相互作用，并且与单个共价配体对应物相比，腺苷受体亚型选择性更高。
• Development of Covalent, Clickable Probes for Adenosine A₁ and A₃ Receptors
  作者：Phuc N. H. Trinh、Daniel J. W. Chong、Katie Leach、Stephen J. Hill、Joel D. A. Tyndall、Lauren T. May、Andrea J. Vernall、Karen J. Gregory

  DOI：10.1021/acs.jmedchem.0c02169

  日期：2021.6.24
• Fluorosulfonyl-Substituted Xanthines as Selective Irreversible Antagonists for the A₁-Adenosine Receptor
  作者：Anthony R. Beauglehole、Stephen P. Baker、Peter J. Scammells

  DOI：10.1021/jm000181f

  日期：2000.12.1

  FSCPX (1) has been reported to be a potent, selective, and irreversible antagonist for the A(1)-adenosine receptor (AR). To obtain an irreversible A(1)AR antagonist with potentially better stability and to further elucidate the effects of linker structure on the pharmacological characteristics, several new analogues were targeted in which the labile ester linkage of 1 was replaced by more stable functionalities. In particular, alkyl and:amide linkers between the xanthine pharmacophore and the reactive 4-fluorosulfonylphenyl group were explored. The data showed that the chemical composition of the linker affects the affinity and apparent irreversible binding to the A(1)AR. Overall, compound 23b appeared to have the most advantageous characteristics as a potential irreversible ligand for the A(1)AR. These include relatively high affinity for the A(1)AR. as compared to the A(2A)AR, concentration-dependent and selective apparent irreversible binding to the A(1)AR, and ease;of removal of unbound ligand from biological membranes. These :properties indicate that 23b has the potential to be a useful tool for further study of the structure and function of the A(1)AR.
• A Chemical Biological Approach to Study G Protein-Coupled Receptors: Labeling the Adenosine A₁ Receptor Using an Electrophilic Covalent Probe
  作者：Bert L. H. Beerkens、Çağla Koç、Rongfang Liu、Bogdan I. Florea、Sylvia E. Le Dévédec、Laura H. Heitman、Adriaan P. IJzerman、Daan van der Es

  DOI：10.1021/acschembio.2c00589

  日期：2022.11.18