(E)-3-hydroxy-N′-(1-(naphthalen-2-yl)ethylidene)naphthalene-2-carbohydrazide | 1393656-31-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (E)-3-hydroxy-N′-(1-(naphthalen-2-yl)ethylidene)naphthalene-2-carbohydrazide
• 英文别名: (E)-3-hydroxy-N'-(1-(naphthalene-2-yl)ethylidene)-2-naphthohydrazide；3-hydroxy-N'-[1-(2-naphthyl)ethylidene]-2-naphthohydrazide；3-hydroxy-N-[(E)-1-naphthalen-2-ylethylideneamino]naphthalene-2-carboxamide
• CAS: 1393656-31-9
• 化学式: C₂₃H₁₈N₂O₂
• 分子量: 354.408
• InChiKey: BQKMWIRDJFJAJX-BUVRLJJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-羟基-3-萘甲酸 在 盐酸 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 7.25h， 生成 (E)-3-hydroxy-N′-(1-(naphthalen-2-yl)ethylidene)naphthalene-2-carbohydrazide
  参考文献：
  名称：

  Study of E/Z Isomerization in a Series of Novel Non-ligand Binding Pocket Androgen Receptor Antagonists

  摘要：

  We report the conformational analysis of a series of 3-hydroxy-N'-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazides. This class of compounds has recently been reported as androgen receptor (AR)-coactivator disruptors for potential application in prostate cancer therapy. Definition of the E/Z isomerism around the imine linker group (hydrazide) is significant from a mechanistic point of view. A detailed study using theoretical calculations coupled with experimental techniques has allowed us determine an initial preference for the E isomer. The biological activity of newly synthesized compounds at the androgen receptor, along with a series of structural analogs, was determined and provides the basis for preliminary qualitative structure-activity relationship analysis.

  DOI：

  10.1021/ci300299n

文献信息

• Synthesis of 3‐hydroxy‐2‐naphthohydrazide‐based hydrazones and their implications in diabetic management via in vitro and in silico approaches
  作者：Mussarat Tasleem、Saeed Ullah、Sobia Ahsan Halim、Ifra Urooj、Nadeem Ahmed、Rabia Munir、Ajmal Khan、Attalla F. El‐kott、Parham Taslimi、Sally Negm、Ahmed Al‐Harrasi、Zahid Shafiq

  DOI：10.1002/ardp.202300544

  日期：2024.2

  Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, “α‐glucosidase.” Several approaches including fourier transform infrared, ¹H NMR, and ¹³C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a–3p displayed more effective inhibitory activities against α‐glucosidase with IC₅₀ in a range of 2.80–29.66 µM as compared with the commercially available inhibitor, acarbose (IC₅₀ = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC₅₀ value of 2.80 ± 0.03 µM, followed by 3i (IC₅₀ = 4.13 ± 0.06 µM), 3f (IC₅₀ = 5.18 ± 0.10 µM), 3c (IC₅₀ = 5.42 ± 0.11 µM), 3g (IC₅₀ = 6.17 ± 0.15 µM), 3d (IC₅₀ = 6.76 ± 0.20 µM), 3a (IC₅₀ = 9.59 ± 0.14 µM), and 3n (IC₅₀ = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration‐dependent form of inhibition by 3h with K_i value = 4.76 ± 0.0068 µM. Additionally, an in silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene‐ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α‐glucosidase enzyme.

  摘要 糖尿病（DM）是一种慢性疾病，由于其后果多、发病率高，已成为一个严重的全球健康问题。我们合成了一系列腙类衍生物，并通过抑制重要的碳水化合物分解酶 "α-葡萄糖苷酶 "测试了它们的抗糖尿病潜力。利用傅立叶变换红外光谱、1H NMR 和 13C NMR 等多种方法确认了所有合成衍生物的结构。化合物 3a-3p 的体外分析表明，与市售抑制剂阿卡波糖（IC50 = 873.34 ± 1.67 M）相比，其对α-葡萄糖苷酶的抑制活性更强，IC50 在 2.80-29.66 µM 之间。化合物 3h 显示出最高的抑制潜力，IC50 值为 2.80 ± 0.03 µM，其次是 3i（IC50 = 4.13 ± 0.06 µM）、3f（IC50 = 5.18 ± 0.10 µM）、3c（IC50 = 5.42 ± 0.11 µM）、3g（IC50 = 6.17 ± 0.15 µM）、3d（IC50 = 6.76 ± 0.20 µM）、3a（IC50 = 9.59 ± 0.14 µM）和 3n（IC50 = 10.01 ± 0.42 µM）。对最强化合物 3h 的动力学分析表明，3h 的抑制作用与浓度有关，Ki 值 = 4.76 ± 0.0068 µM。此外，还采用了一种硅学对接方法来预测所有化合物的结合模式，结果表明，酰肼和萘酚基团在化合物与α-葡萄糖苷酶的重要残基（即 Glu277 和 Gln279）结合过程中发挥了重要作用。
• Exploring naphthyl-carbohydrazides as inhibitors of influenza A viruses
  作者：Sanmitra Barman、Lei You、Ran Chen、Vlad Codrea、Grace Kago、Ramakrishna Edupuganti、Jon Robertus、Robert M. Krug、Eric V. Anslyn

  DOI：10.1016/j.ejmech.2013.10.063

  日期：2014.1

  A library of hydrazide derivatives was synthesized to target non-structural protein 1 of influenza A virus (NS1) as a means to develop anti-influenza drug leads. The lead compound 3-hydroxy-N-[(Z)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)ethylideneamino]naphthalene-2-carboxamide, which we denoted as "HENC", was identified by its ability to increase the melting temperature of the effector domain (ED) of the NS1 protein, as assayed using differential scanning fluorimetry. A library of HENC analogs was tested for inhibitory effect against influenza A virus replication in MDCK cells. A systematic diversification of HENC revealed the identity of the R group attached to the imine carbon atom significantly influenced the antiviral activity. A phenyl or cyclohexyl at this position yielded the most potent antiviral activity. The phenyl containing compound had antiviral activity similar to that of the active form of oseltamivir (Tamiflu), and had no detectable effect on cell viability. (C) 2013 Elsevier Masson SAS. All rights reserved.
• ANDROGEN RECEPTOR LIGANDS
  申请人：Lloyd David George

  公开号：US20140357682A1

  公开（公告）日：2014-12-04

  Non ligand binding pocket antagonists for the human androgen receptor. The androgen receptor (AR) is a member of the Nuclear Receptor (NR) family and its role is to modulate the biological effects of the endogenous androgens, testosterone (tes) and dihydrotestosterone (DHT). Synthetic androgens and anti-androgens have therapeutic value in the treatment of various androgen dependent conditions, from regulation of male fertility to prostate cancer. Current treatment of prostate cancer (PCa) typically involves administration of ‘classical’ antiandrogens, competitive inhibitors of natural AR ligands, DHT and tes, for the ligand binding pocket (LBP) in the C-terminal ligand binding domain (LBD) of the AR. However, prolonged LBP-targeting can often lead to androgen resistance and alternative therapies and therapeutic strategies are urgently required. Disclosed herein are a class of non-steroidal, small molecule AR antagonists which inhibit the transcriptional activity of the AR by non LBP-mediated modulation. The novel class reported demonstrates full (‘true’) antagonism in AR with low micromolar potency, high selectivity over both the Estrogen Receptors alpha and beta (ERα and ERβ) and the Glucocorticoid Receptor (GR) and only micromolar partial antagonism in the Progesterone Receptor (PR). Data provide compelling evidence for such non-LBP intervention as an alternative approach to classical PCa therapy. (Formula I).
• US9296716B2
  申请人：——

  公开号：US9296716B2

  公开（公告）日：2016-03-29
• [EN] ANDROGEN RECEPTOR LIGANDS<br/>[FR] LIGANDS DU RÉCEPTEUR DES ANDROGÈNES
  申请人：PROVOST FELLOWS & SCHOLARS COLLEGE OF THE HOLY UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

  公开号：WO2013076275A1

  公开（公告）日：2013-05-30

  Non ligand binding pocket antagonists for the human androgen receptor. The androgen receptor (AR) is a member of the Nuclear Receptor (NR) family and its role is to modulate the biological effects of the endogenous androgens, testosterone (tes) and dihydrotestosterone (DHT). Synthetic androgens and anti-androgens have therapeutic value in the treatment of various androgen dependent conditions, from regulation of male fertility to prostate cancer. Current treatment of prostate cancer (PCa) typically involves administration of 'classical' antiandrogens, competitive inhibitors of natural AR ligands, DHT and tes, for the ligand binding pocket (LBP) in the C-terminal ligand binding domain (LBD) of the AR. However, prolonged LBP-targeting can often lead to androgen resistance and alternative therapies and therapeutic strategies are urgently required. Disclosed herein are a class of non-steroidal, small molecule AR antagonists which inhibit the transcriptional activity of the AR by non LBP-mediated modulation. The novel class reported demonstrates full ('true') antagonism in AR with low micromolar potency, high selectivity over both the Estrogen Receptors alpha and beta (ERα and ERβ) and the Glucocorticoid Receptor (GR) and only micromolar partial antagonism in the Progesterone Receptor (PR). Data provide compelling evidence for such non-LBP intervention as an alternative approach to classical PCa therapy. (Formula I).