methyl 3-bromo-5-formyl-2-hydroxybenzoate | 861514-69-4

• 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: methyl 3-bromo-5-formyl-2-hydroxybenzoate
• 英文别名: Methyl 3-bromo-5-formyl-2-hydroxybenzoate
• CAS: 861514-69-4
• 化学式: C₉H₇BrO₄
• 分子量: 259.056
• InChiKey: AXCLGKCRWIAMPH-UHFFFAOYSA-N

物化性质

• 熔点：
  114 °C
• 沸点：
  307.6±42.0 °C(Predicted)
• 密度：
  1.686±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-bromo-5-formyl-2-hydroxybenzoate 在 三乙基硅烷 、 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 furan-2-carboxylic acid (4-{[3-bromo-5-(2-chlorobenzyl)-2-hydroxybenzylidene]amino}phenyl)amide
  参考文献：
  名称：

  Ligand efficiency based approach for efficient virtual screening of compound libraries

  摘要：

  Here we report for the first time the use of fit quality (FQ), a ligand efficiency (LE) based measure for virtual screening (VS) of compound libraries. The LE based VS protocol was used to screen an in-house database of 125,000 compounds to identify aurora kinase A inhibitors. First, 20 known aurora kinase inhibitors were docked to aurora kinase A crystal structure (PDB ID: 2W1C); and the conformations of docked ligand were used to create a pharmacophore (PH) model. The PH model was used to screen the database compounds, and rank (PH rank) them based on the predicted IC50 values. Next, LE_Scale, a weight-dependant LE function, was derived from 294 known aurora kinase inhibitors. Using the fit quality (FQ = LE/LE_Scale) score derived from the LE_Scale function, the database compounds were reranked (PH_FQ rank) and the top 151 (0.12% of database) compounds were assessed for aurora kinase A inhibition biochemically. This VS protocol led to the identification of 7 novel hits, with compound 5 showing aurora kinase A IC50 = 1.29 μM. Furthermore, testing of 5 against a panel of 31 kinase reveals that it is selective toward aurora kinase A & B, with <50% inhibition for other kinases at 10 μM concentrations and is a suitable candidate for further development. Incorporation of FQ score in the VS protocol not only helped identify a novel aurora kinase inhibitor, 5, but also increased the hit rate of the VS protocol by improving the enrichment factor (EF) for FQ based screening (EF = 828), compared to PH based screening (EF = 237) alone. The LE based VS protocol disclosed here could be applied to other targets for hit identification in an efficient manner.

  DOI：

  10.1016/j.ejmech.2014.06.029
• 作为产物：
  描述：

  5-甲酰基水杨酸甲酯 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以67%的产率得到methyl 3-bromo-5-formyl-2-hydroxybenzoate
  参考文献：
  名称：

  单和二水杨酸衍生物：PTP1B抑制剂可作为潜在的抗肥胖药。

  摘要：

  合成了一系列包含一个或两个水杨酸部分的化合物，并研究了其抑制PTP1B磷酸水解酶活性的功效。一些亚甲基二水杨酸衍生物是PTP1B的有效抑制剂。在这些衍生物中，3c对TC-PTP表现出约14倍的选择性，并在小鼠模型中测试了该化合物预防饮食引起的肥胖的功效。它有效地抑制了体重和脂肪的增加，而没有任何明显的毒性作用。该化合物还可以防止血浆甘油三酸酯，胆固醇和非酯化脂肪酸浓度的增加。因此，将其治疗潜力扩展到其他相关的代谢性疾病，例如高脂血症和高胆固醇血症。

  DOI：

  10.1016/j.bmc.2007.07.010

文献信息

• 4-Phenyl-5-Oxo-1,4,5,6,7,8,- Hexahydroquinoline Derivatives as Medicaments for the Treatment of Infertility
  申请人：Timmers Cornelis Marius

  公开号：US20080300270A1

  公开（公告）日：2008-12-04

  The invention relates to a 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to Formula (I), wherein the substituents are defined as in the description, or a pharmaceutically salt thereof. The compounds of this invention are potent FSH receptor activators and may be used for treating fertility disorders in e.g. controlled ovarian hyperstimulation and IVF procedures.

  该发明涉及一种根据式(I)定义的4-苯基-5-酮-1,4,5,6,7,8-六氢喹啉衍生物，其中取代基如描述中所定义，或其药用盐。本发明的化合物是强效FSH受体激活剂，可用于治疗例如控制性卵巢过度刺激和体外受精程序中的生育障碍。
• Derivatives of 1,4-bis(3-hydroxycarbonyl-4-hydroxyl)styrylbenzene as PTP1B inhibitors with hypoglycemic activity
  作者：Suja Shrestha、Bharat Raj Bhattarai、Bhooshan Kafle、Keun-Hyeung Lee、Hyeongjin Cho

  DOI：10.1016/j.bmc.2008.07.090

  日期：2008.9

  Disalicylic acid derivatives with stilbene and bis-styrylbenzene skeleton were synthesized as PTP1B inhibitors. The most potent in this series exhibited a submicromolar IC(50) value. One of the compounds 7b was tested in an animal model for its efficacy as an anti-diabetic or an anti-obesity agent. In feeding compound 7b to diet-induced obese mice, no significant differences in weight gain and food

  合成具有二苯乙烯和双苯乙烯基骨架的二水杨酸衍生物作为PTP1B抑制剂。该系列中最有效的药物表现出亚微摩尔IC（50）值。在动物模型中测试了化合物7b之一作为抗糖尿病药或抗肥胖药的功效。在向饮食诱导的肥胖小鼠饲喂化合物7b时，在药物治疗的小鼠和肥胖的对照小鼠之间未观察到体重增加和食物消耗的显着差异。然而，在肥胖诱导的糖尿病小鼠中，7b显着降低了空腹血糖水平并改善了葡萄糖耐量。
• [EN] WDR5 INHIBITORS AND MODULATORS<br/>[FR] MODULATEURS ET INHIBITEURS DE WDR5
  申请人：UNIV VANDERBILT

  公开号：WO2020247679A1

  公开（公告）日：2020-12-10

  Quinazolin-4(3H)-one, 2,3 -dihydroquinazolin-4(1H)-one, 3,4-dihydrobenzo[f][1,4]oxazepin- 5(2H)-one, and 3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione compounds and derivatives inhibit WDR5 and associated protein-protein interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.

  喹唑啉-4(3H)-酮，2,3-二氢喹唑啉-4(1H)-酮，3,4-二氢苯并[f][1,4]噁唑啉-5(2H)-酮，以及3,4-二氢-1H-苯并[e][1,4]二氮杂环己二酮化合物及其衍生物抑制WDR5及相关蛋白质相互作用，这些化合物及其药物组合物可用于治疗受试者的疾病和症状，如癌细胞增殖。
• 4-phenyl-5-OXO-1,4,5,6,7,8-hexahydroquinoline derivatives as medicaments for the treatment of infertility
  申请人：N.V. Organon

  公开号：US08034945B2

  公开（公告）日：2011-10-11

  The invention relates to a 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to Formula (I), wherein the substituents are defined as in the description, or a pharmaceutically salt thereof. The compounds of this invention are potent FSH receptor activators and may be used for treating fertility disorders in e.g. controlled ovarian hyperstimulation and IVF procedures.

  本发明涉及一种4-苯基-5-氧代-1,4,5,6,7,8-六氢喹啉衍生物，其化学式为（I），其中取代基如描述中所定义，或其药学盐。本发明的化合物是有效的FSH受体激动剂，可用于治疗生育障碍，例如控制性卵巢过度刺激和体外受精程序。
• Structure-Based Discovery of Potent, Orally Bioavailable Benzoxazepinone-Based WD Repeat Domain 5 Inhibitors
  作者：Kevin B. Teuscher、Jonathan J. Mills、Jianhua Tian、Changho Han、Kenneth M. Meyers、Jiqing Sai、Taylor M. South、Mackenzie M. Crow、Mayme Van Meveren、John L. Sensintaffar、Bin Zhao、Kangsa Amporndanai、William J. Moore、Gordon M. Stott、William P. Tansey、Taekyu Lee、Stephen W. Fesik

  DOI：10.1021/acs.jmedchem.3c01529

  日期：2023.12.28

  chromatin-associated protein WDR5 (WD repeat domain 5) is an essential cofactor for MYC and a conserved regulator of ribosome protein gene transcription. It is also a high-profile target for anti-cancer drug discovery, with proposed utility against both solid and hematological malignancies. We have previously discovered potent dihydroisoquinolinone-based WDR5 WIN-site inhibitors with demonstrated efficacy

  染色质相关蛋白 WDR5（WD 重复结构域 5）是 MYC 的重要辅助因子，也是核糖体蛋白基因转录的保守调节因子。它也是抗癌药物发现的一个备受瞩目的目标，有望用于对抗实体瘤和血液恶性肿瘤。我们之前发现了基于二氢异喹啉酮的有效 WDR5 WIN 位点抑制剂，并在动物模型中证明了其有效性和安全性。在这项研究中，我们试图优化双环核心，以发现一系列新型 WDR5 WIN 位点抑制剂，其效力和理化性质均得到改善。我们确定了 3,4-二氢苯并[ f ][1,4]oxazep​​in-5(2 H )-one 核心作为有效 WDR5 抑制剂的替代支架。此外，我们使用X射线结构分析来设计部分饱和的双环P 7单元。与我们同类最佳的基于二氢异喹啉酮的抑制剂相比，这些基于苯并氧氮杂酮的抑制剂表现出更高的细胞效力和选择性以及良好的理化性质。这项研究为发现更先进的 WDR5 WIN 位点抑制剂开辟了途径，并支持它们作为新型抗癌疗法的发展。