N-(4-叔丁基苯基)-5-氯-2-羟基苯甲酰胺 | 634186-02-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(4-叔丁基苯基)-5-氯-2-羟基苯甲酰胺
• 英文名称: Benzamide, 5-chloro-N-[4-(1,1-dimethylethyl)phenyl]-2-hydroxy-
• 英文别名: N-(4-tert-butylphenyl)-5-chloro-2-hydroxybenzamide
• CAS: 634186-02-0
• 化学式: C₁₇H₁₈ClNO₂
• 分子量: 303.788
• InChiKey: BHGHGMWWTKJTQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-叔丁基苯基)-5-氯-2-羟基苯甲酰胺 、 氯甲酸甲酯 以 吡啶 为溶剂， 反应 1.0h， 以61%的产率得到3-(4-Tert-butylphenyl)-6-chloro-1,3-benzoxazine-2,4-dione
  参考文献：
  名称：

  抗结核药物的定向开发（第二部分）：卤代3-（4-烷基苯基）-1,3-苯并恶嗪-2,4-（3H）-二酮

  摘要：

  基于我们之前的研究，通过水杨酰苯胺和氯甲酸甲酯的反应合成了21个新的卤代3-(4-烷基苯基)-1,3-苯并恶嗪-2,4-(3H)-二酮。所有化合物均在体外针对三种不同的分枝杆菌菌株进行筛选，并使用 Free-Wilson 方法建立构效关系。6-溴-3-(4-丁基苯基)-1,3-苯并恶嗪-2,4-(3H)-二酮3b被证明是该系列中活性最强的化合物。

  DOI：

  10.1002/ardp.200600002
• 作为产物：
  描述：

  5-氯代水杨酸 、 4-叔丁基苯胺 在 三氯化磷 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以73%的产率得到N-(4-叔丁基苯基)-5-氯-2-羟基苯甲酰胺
  参考文献：
  名称：

  抗结核药物的定向开发：水杨酰苯胺

  摘要：

  根据我们之前的结果，合成了 22 种水杨酰苯胺。测试了这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌的体外抗分枝杆菌活性。Free-Wilson 方法用于评估结构-抗分枝杆菌活性关系。选择 4-氯-N-（4-丙基苯基）水杨酰胺和 5-氯-N-（4-丙基苯基）水杨酰胺进行临床前研究。

  DOI：

  10.1002/ardp.200600093

文献信息

• Structure–activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling
  作者：Ill-Young Lee、Todd D. Gruber、Amanda Samuels、Minhan Yun、Bora Nam、Minseo Kang、Kathryn Crowley、Benjamin Winterroth、Helena I. Boshoff、Clifton E. Barry

  DOI：10.1016/j.bmc.2012.10.056

  日期：2013.1

  A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics. Published by Elsevier Ltd.
• Identification and synthesis of low-molecular weight cholecystokinin B receptor (CCKBR) agonists as mediators of long-term synaptic potentiation
  作者：Yanmei Zhang、Yican Wang、Yiping Guo、Jinxi Liao、Zhengchao Tu、Yongzhi Lu、Ke Ding、Micky D. Tortorella、Jufang He

  DOI：10.1007/s00044-019-02292-x

  日期：2019.3

  Recently, He et al. reported that CCKB receptors located in the neocortex of the brain when bound to their bound natural ligand, CCK peptides, enhance memory, bringing up the possibility that agonists targeting the CCKB receptor may act as therapeutic agents in diseases in which memory loss is marked as observed in dementia and Alzheimer's. In this report, we describe the synthesis of novel low-molecular weight benzoamine CCKB receptor agonists. The compounds made in this series were determined to be mostly partial agonists, although some antagonists were identified, as well, capable of triggering calcium release in a cell line that overexpresses the CCKB receptor. Compound 35 demonstrated an EC50 of 0.15 mu M in the cell-based assay, but more importantly, several of the compounds, including 35, demonstrated a physiological effect, inducing long-term potentiation in rat brains comparable to the CCK-8 peptide albeit at much higher concentrations. Based on these findings, benzoamines may be the basis for a new series of CCKB receptor agonists in drug-discovery efforts that seek to develop therapeutics to prevent memory loss.
• The Oriented Development of Antituberculotics: Salicylanilides
  作者：Karel Waisser、Josef Matyk、Hana Divišová、Petra Husáková、Jirí Kuneš、Vera Klimešová、Jarmila Kaustová、Ute Möllmann、Hans-Martin Dahse、Milan Miko

  DOI：10.1002/ardp.200600093

  日期：2006.11

  On the basis of our previous results 22 salicylanilides were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. The Free‐Wilson method was used to evaluate structure‐antimycobacterial activity relationships. 4‐Chloro‐N‐(4‐propylphenyl)salicylamide and 5‐chloro‐N‐(4‐propylphenyl)salicylamide

  根据我们之前的结果，合成了 22 种水杨酰苯胺。测试了这些化合物对结核分枝杆菌、堪萨斯分枝杆菌和鸟分枝杆菌的体外抗分枝杆菌活性。Free-Wilson 方法用于评估结构-抗分枝杆菌活性关系。选择 4-氯-N-（4-丙基苯基）水杨酰胺和 5-氯-N-（4-丙基苯基）水杨酰胺进行临床前研究。
• The Oriented Development of Antituberculotics (Part II): Halogenated 3-(4-Alkylphenyl)-1,3-benzoxazine-2,4-(3H)-diones
  作者：Karel Waisser、Josef Matyk、Hana Divišová、Petra Husáková、Jirí Kuneš、Vera Klimešová、Karel Palát、Jarmila Kaustová

  DOI：10.1002/ardp.200600002

  日期：2007.5

  Based on our previous studies, 21 new halogenated 3‐(4‐alkylphenyl)‐1,3‐benzoxazine‐2,4‐(3H)‐diones were synthesized by the reaction of salicylanilides and methyl‐chloroformate. All compounds were screened in vitro against three different strains of mycobacterium, and Free‐Wilson method was used to establish structure‐activity relationships. 6‐Bromo‐3‐(4‐butylphenyl)‐1,3‐benzoxazine‐2,4‐(3H)‐dione

  基于我们之前的研究，通过水杨酰苯胺和氯甲酸甲酯的反应合成了21个新的卤代3-(4-烷基苯基)-1,3-苯并恶嗪-2,4-(3H)-二酮。所有化合物均在体外针对三种不同的分枝杆菌菌株进行筛选，并使用 Free-Wilson 方法建立构效关系。6-溴-3-(4-丁基苯基)-1,3-苯并恶嗪-2,4-(3H)-二酮3b被证明是该系列中活性最强的化合物。