苯甲酸,4-[(4-氟苯甲酰)氨基]-,乙基酯 | 172950-63-9

• 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: 苯甲酸,4-[(4-氟苯甲酰)氨基]-,乙基酯
• 英文名称: ethyl 4-(4-fluorobenzamido)benzoate
• 英文别名: 4-(4-fluorobenzoylamino)benzoic acid ethyl ester；ethyl 4-[(4-fluorobenzoyl)amino]benzoate
• CAS: 172950-63-9
• 化学式: C₁₆H₁₄FNO₃
• 分子量: 287.29
• InChiKey: YJIRBZOMHWYLAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯甲酸,4-[(4-氟苯甲酰)氨基]-,乙基酯 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 4-[(4-fluorobenzoyl)amino]-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]benzamide
  参考文献：
  名称：

  Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors

  摘要：

  Fifteen novel sulfathiazole-related compounds were designed as PTP1B inhibitors based on a previously reported allosteric inhibitor (1) of PTP1B. These compounds were synthesized and evaluated against human recombinant PTP1B. Six compounds (3, 4, 8 and 14-16) exhibited significant inhibitory activity against PTP1B. The most active compound (16) showed IC50 value of 3.2 mu M and kinetic analysis indicated that it is a non-competitive inhibitor of PTP1B. Furthermore, compound 16 demonstrated excellent selectivity to PTP1B over other PTPs. It also displayed in vivo insulin sensitizing effect in the insulin resistant mice. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.073
• 作为产物：
  描述：

  对氨基苯甲酸 在 硫酸 、 三苯基二氯化膦 作用下， 以 氯仿 为溶剂， 反应 16.25h， 生成 苯甲酸,4-[(4-氟苯甲酰)氨基]-,乙基酯
  参考文献：
  名称：

  PTG-0861：一种新型HDAC6选择性抑制剂，作为急性髓细胞性白血病的治疗策略。

  摘要：

  在多种人类病理学中失调的组蛋白脱乙酰基酶（HDAC）活性突显了这一表观遗传酶家族作为关键的可药物靶向，适合小分子干预。尽管有效，但目前使用非选择性HDAC抑制剂（HDACi）的方法已显示出一系列不良的临床毒性。为了避免这种情况，最近的努力集中在设计高选择性HDACi作为一种新的治疗策略上。除了在调节转录中的作用外，独特的HDAC6（具有两个催化结构域）还调节了HDAC6的脱乙酰基作用。α-微管蛋白; 促进生长因子控制的细胞运动，细胞分裂和转移标志。最近的研究已将HDAC6异常功能与包括急性髓细胞性白血病和多发性骨髓瘤在内的多种血液学癌症联系起来。本文中，我们报告了新型PDAC-0861（JG-265）的发现，体外表征和生物学评估，PTG-0861是新型HDAC6选择性抑制剂，具有强同工酶选择性（〜36×）和低纳摩尔 浓度（IC 50 = 6 nM） ）针对HDAC6。通过计算机对接研究对这

  DOI：

  10.1016/j.ejmech.2020.112411

文献信息

• Design, synthesis, and activity evaluation of broad-spectrum small-molecule inhibitors of anti-apoptotic Bcl-2 family proteins: Characteristics of broad-spectrum protein binding and its effects on anti-tumor activity
  作者：Can-Hui Zheng、Hui Yang、Meng Zhang、Shi-Hai Lu、Duo Shi、Juan Wang、Xiu-Hua Chen、Xiao-Hui Ren、Jia Liu、Jia-Guo Lv、Ju Zhu、You-Jun Zhou

  DOI：10.1016/j.bmcl.2011.11.101

  日期：2012.1

  than ABT-737 at inhibiting growth in multiple tumor cell lines known to express Bcl-xL, Bcl-2, and Mcl-1 proteins at high levels. Compounds B-11 and B-12 had the strongest anti-tumor activity of any compounds we produced. This study suggests that it is feasible to design small-molecule inhibitors based on the structure of Bim BH3, which shows broad-spectrum binding to Bcl-xL, Bcl-2, and Mcl-1 proteins

  在比较Bim BH3：Bcl-x L络合物和ABT-737：Bcl-x L络合物的结构的基础上，设计了一系列A类化合物。这些化合物具有ABT-737的基本骨架和Bim BH3的h2残基。在饱和诱变测定中，这些残基已显示出与Bim BH3的广谱结合特性有关。与作为Bcl-2蛋白家族抗凋亡成员的选择性抑制剂的ABT-737不同，A类化合物对目标蛋白具有广谱结合活性，类似于Bim BH3肽。然后通过修饰最有效的A类化合物的结构来合成B类化合物化合物A - 4。这些大多数B类化合物显示出比A类化合物更好的与靶蛋白的结合亲和力。他们还显示出比ABT-737更有效地抑制已知以高水平表达Bcl-x L，Bcl-2和Mcl-1蛋白的多种肿瘤细胞的生长。在我们生产的所有化合物中，化合物B - 11和B - 12具有最强的抗肿瘤活性。这项研究表明，根据Bim BH3的结构设计小分子抑制剂是可行的，该结构显示了与Bcl-x
• Derivatives of 3-Azabicyclo[3.1.0] Hexane as Dipeptidyl Peptidase-IV Inhibitors
  申请人：Sattigeri Jitendra A.

  公开号：US20080300251A1

  公开（公告）日：2008-12-04

  The present invention relates to novel 3-azabicyclo[3.1.0]hexane derivatives as dipeptidyl peptidase-IV inhibitors and the processes for the synthesis of the said compounds. This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating diabetes, especially type 2 diabetes, as well as prediabetes, diabetic dyslipidemia, metabolic acidosis, ketosis, satiety disorders, and obesity. These inhibitors can also be used to treat conditions manifested by a variety of metabolic, neurological, anti-inflammatory, and autoimmune disorders like inflammatory disease, multiple sclerosis, rheumatoid arthritis; viral, cancer and gastrointestinal disorders. The compounds of this invention can also be used for treatment of infertility arising due to polycystic ovary syndrome.

  本发明涉及作为二肽基肽酶-IV抑制剂的新型3-氮杂双环[3.1.0]己烷衍生物以及所述化合物的合成方法。本发明还涉及含有本发明化合物的药理组合物，以及治疗糖尿病，特别是2型糖尿病，以及糖尿病前期、糖尿病脂质代谢紊乱、代谢性酸中毒、酮症、饱腹障碍和肥胖的方法。这些抑制剂还可用于治疗多种代谢、神经、抗炎和自身免疫性疾病的症状，如炎症性疾病、多发性硬化症、类风湿关节炎；病毒性、癌症和胃肠道疾病。本发明的化合物还可用于治疗由多囊卵巢综合征引起的不孕症。
• [EN] AMIDE DERIVATIVES AND THEIR USE AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1<br/>[FR] DERIVES AMIDO ET LEUR UTILISATION COMME INHIBITEURS DE LA 11-BETA-HYDROXYSTEROIDE DESHYDROGENASE DE TYPE 1
  申请人：NOVARTIS AG

  公开号：WO2004065351A1

  公开（公告）日：2004-08-05

  Compounds of the formula (I) provide pharmacological agents which lower intracellular glucocorticoid concentrations in mammals, in particular, intracellular cortisol levels in humans. Therefore, the compounds of the instant invention improve insulin sensitivity in the muscle and the adipose tissue, and reduce lipolysis and free fatty acid production in the adipose tissue. The compounds of the invention lower hepatic glucocorticoid concentration in mammals, in particular, hepatic cortisol concentration in humans, resulting in inhibition of hepatic gluconeogenesis and lowering of plasma glucose levels. Thus, the compounds of the instant invention may be particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which hyperglycemia and/or insulin resistance are implicated, such as type-2 diabetes. The compounds of the invention may also be used to treat other glucocorticoid associated disorders, such as Syndrome-X, dyslipidemia, hypertension and central obesity. The invention furthermore relates to the use of the compounds according to the invention for the preparation of medicaments, in particular of medicaments useful for the treatment and prevention of glucocorticoid associated disorders, by improving insulin sensitivity, reducing plasma glucose levels, reducing lipolysis and free fatty acid production, and by decreasing visceral adipose tissue formation.

  化合物的化学式（I）提供了降低哺乳动物细胞内糖皮质激素浓度的药物，特别是降低人类细胞内皮质醇水平的药物。因此，本发明的化合物改善了肌肉和脂肪组织中的胰岛素敏感性，并减少了脂肪组织中的脂解和游离脂肪酸产生。本发明的化合物降低了哺乳动物肝脏内的糖皮质激素浓度，特别是降低了人类肝脏内的皮质醇浓度，从而抑制了肝葡萄糖生成和降低了血浆葡萄糖水平。因此，本发明的化合物可能特别适用于哺乳动物作为降糖药物，用于治疗和预防高血糖和/或胰岛素抵抗等疾病，如2型糖尿病。本发明的化合物还可用于治疗其他与糖皮质激素相关的疾病，如X综合症、血脂异常、高血压和中心性肥胖。此外，本发明还涉及根据本发明的化合物用于制备药物，特别是用于治疗和预防与糖皮质激素相关疾病的药物，通过改善胰岛素敏感性、降低血浆葡萄糖水平、减少脂解和游离脂肪酸产生，以及减少内脏脂肪组织形成。
• Amide derivatives and their use as inhibitors of 11-beta-hydroxysteroid dehydrogenase type I
  申请人：Coppola Mark Gary

  公开号：US20060205772A1

  公开（公告）日：2006-09-14

  Compounds of the formula (I) provide pharmacological agents which lower intracellular glucocorticoid concentrations in mammals, in particular, intracellular cortisol levels in humans. Therefore, the compounds of the instant invention improve insulin sensitivity in the muscle and the adipose tissue, and reduce lipolysis and free fatty acid production in the adipose tissue. The compounds of the invention lower hepatic glucocorticoid concentration in mammals, in particular, hepatic cortisol concentration in humans, resulting in inhibition of hepatic gluconeogenesis and lowering of plasma glucose levels. Thus, the compounds of the instant invention may be particularly useful in mammals as hypoglycemic agents for the treatment and prevention of conditions in which hyperglycemia and/or insulin resistance are implicated, such as type-2 diabetes. The compounds of the invention may also be used to treat other glucocorticoid associated disorders, such as Syndrome-X, dyslipidemia, hypertension and central obesity. The invention furthermore relates to the use of the compounds according to the invention for the preparation of medicaments, in particular of medicaments useful for the treatment and prevention of glucocorticoid associated disorders, by improving insulin sensitivity, reducing plasma glucose levels, reducing lipolysis and free fatty acid production, and by decreasing

  化合物(I)的配方提供了降低哺乳动物细胞内糖皮质激素浓度的药物，特别是降低人类细胞内皮质醇水平的药物。因此，本发明的化合物改善了肌肉和脂肪组织中的胰岛素敏感性，并减少了脂肪组织中的脂解和游离脂肪酸产生。本发明的化合物降低了哺乳动物肝脏中的糖皮质激素浓度，特别是人类肝脏中的皮质醇浓度，从而抑制了肝糖异生并降低了血浆葡萄糖水平。因此，本发明的化合物在哺乳动物中可能特别有用作为降糖药物，用于治疗和预防与高血糖和/或胰岛素抵抗有关的疾病，例如2型糖尿病。本发明的化合物还可用于治疗其他与糖皮质激素相关的疾病，例如综合征X、血脂异常、高血压和中心性肥胖。此外，本发明还涉及使用根据本发明的化合物制备药物，特别是用于改善胰岛素敏感性、降低血浆葡萄糖水平、减少脂解和游离脂肪酸产生，并通过降低糖皮质激素浓度来降低肝糖异生的药物，用于治疗和预防糖皮质激素相关疾病。
• Synthesis of Phthalimide Derivatives and Their Insecticidal Activity against Caribbean Fruit Fly, Anastrepha suspensa (Loew)
  作者：Fatih Tok、Xiangbing Yang、Nurhayat Tabanca、Bedia Koçyiğit-Kaymakçıoğlu

  DOI：10.3390/biom13020361

  日期：——

  In this study, thirteen phthalimide derivatives were designed and synthesized. All synthesized compounds were evaluated to determine their potential for inhibitory activities against females of the Caribbean fruit fly, Anastrepha suspensa (Loew) (Diptera: Tephritidae). These efforts led to the discovery of three compounds 4a, 4c, and 4d with potent insecticidal activity (LD50 range from 0.70 to 1.91 μg/fly). Among these compounds, 4a exhibited the highest inhibitory potency with 0.70 μg/fly. In addition, in silico models indicated that compound 4a is less toxic than phthalimide and other precursors. Therefore, our results suggest that 4a has strong potential as a candidate component for developing a novel environmentally friendly insecticide for control of pest fruit flies.

  本研究设计并合成了十三种邻苯二甲酰亚胺衍生物。对所有合成的化合物进行了评估，以确定它们对加勒比果蝇 Anastrepha suspensa (Loew)（双翅目：头蝇科）雌蝇的潜在抑制活性。通过这些努力，发现了三种化合物 4a、4c 和 4d，它们具有很强的杀虫活性（半数致死剂量范围为 0.70 至 1.91 微克/只）。在这些化合物中，4a 的抑虫效力最高，为 0.70 微克/只。此外，硅学模型表明，化合物 4a 的毒性低于邻苯二甲酰亚胺和其他前体。因此，我们的研究结果表明，4a 很有可能成为开发新型环境友好型杀虫剂的候选成分，用于控制害虫果蝇。