2-hydroxybenzaldehyde | 20286-84-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-hydroxybenzaldehyde
• 英文别名: tert-butyl (2-hydroxyphenethyl)carbamate；tert-butyl [2-(2-hydroxyphenyl)ethyl]carbamate；Tert-butyl 2-hydroxyphenethylcarbamate；tert-butyl N-[2-(2-hydroxyphenyl)ethyl]carbamate
• CAS: 20286-84-4
• 化学式: C₁₃H₁₉NO₃
• 分子量: 237.299
• InChiKey: FTWBHNHOAIDEOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-hydroxybenzaldehyde 在 1,2-bis(dicyclohexylphosphonium)ethane bis(tetrafluoroborate) 、 palladium diacetate 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、515.03 kPa 条件下， 反应 18.0h， 生成 3,4-二氢异喹啉-1(2H)-酮
  参考文献：
  名称：

  Aminocarbonylation of Aryl Tosylates to Carboxamides

  摘要：

  The palladium - catalyzed aminocarbonylation of aryl tosylates with amines is reported. Suitable conditions were identified by high throughput reaction screening and then further optimized. The substrate scope of the reaction with respect to the aryl tosylate component and the amine component are reported. Competitive aminolysis of the aryl tosylates to afford the amine toluenesulfonamides and the phenol was not observed.

  DOI：

  10.1021/acs.orglett.5b01283
• 作为产物：
  描述：

  2-(2-nitroethyl)phenol 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 2-hydroxybenzaldehyde
  参考文献：
  名称：

  Optimization of the Potency and Pharmacokinetic Properties of a Macrocyclic Ghrelin Receptor Agonist (Part I): Development of Ulimorelin (TZP-101) from Hit to Clinic

  摘要：

  High-throughput screening of Tranzyme Pharma's proprietary macrocycle library using the aequorin Ca2+-bioluminescence assay against the human ghrelin receptor (GRLN) led to the discovery of novel ago fists against this G-protein coupled receptor. Early hits such as 1 (K-i = 86 nM, EC50 = 134 nM) though potent in vitro displayed poor pharmacokinetic properties that required optimization. While such macrocycles are not fully rule-of-five compliant, principally due to their molecular weight and clogP, optimization of their pharmacokinetic properties proved feasible largely through conformational rigidification. Extensive SAR led to the identification of 2 (K-i = 16 nM, EC50 = 29 nM), also known as ulimorelin or TZP-101, which has progressed to phase III human clinical trials for the treatment of postoperative ileus. X-ray structure and detailed NMR studies indicated a rigid peptidomimetic portion in 2 that is best defined as a nonideal type-I' beta-turn. Compound 2 is 24% orally bioavailable in both rats and monkeys. Despite its potency, in vitro and in gastric emptying studies, 2 did not induce growth hormone (GH) release in rats, thus demarcating the GH versus GI pharmacology of GRLN.

  DOI：

  10.1021/jm2007062

文献信息

• LIBRARIES OF DIVERSE MACROCYCLIC COMPOUNDS AND METHODS OF MAKING AND USING THE SAME
  申请人：CYCLENIUM PHARMA INC.

  公开号：US20190153620A1

  公开（公告）日：2019-05-23

  The present disclosure relates to novel macrocyclic compounds and libraries thereof that are useful as research tools for drug discovery efforts. This disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

  本公开涉及新颖的大环化合物及其库，这些化合物可作为药物发现工作的研究工具。本公开还涉及制备这些化合物和库的方法，以及使用这些库的方法，例如在高通量筛选中的应用。特别是，这些库可用于评估现有和新鉴定的药理相关靶点的生物活性，包括G蛋白偶联受体、核受体、酶、离子通道、转运蛋白、转录因子、蛋白质相互作用和核酸-蛋白质相互作用。因此，这些库可应用于寻找用于治疗和预防各种医疗状况的新药物。
• [EN] LIBRARIES OF HETEROARYL-CONTAINING MACROCYCLIC COMPOUNDS AND METHODS OF MAKING AND USING THE SAME<br/>[FR] BIBLIOTHÈQUES DE COMPOSÉS MACROCYCLIQUES CONTENANT HÉTÉROARYLE ET PROCÉDÉS POUR LEUR FABRICATION ET LEUR UTILISATION
  申请人：CYCLENIUM PHARMA INC

  公开号：WO2017049383A1

  公开（公告）日：2017-03-30

  The present disclosure relates to novel macrocyclic compounds and libraries thereof containing heteroaryl moieties that are useful as research tools for drug discovery efforts. The present disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

  本公开涉及新型大环化合物及其库，其中包含对药物发现工作有用的含杂环芳基团的化合物。本公开还涉及制备这些化合物和库的方法，以及使用这些库的方法，例如在高通量筛选中使用。特别是，这些库可用于评估现有和新鉴定的药理学相关靶点的生物活性，包括G蛋白偶联受体、核受体、酶、离子通道、转运蛋白、转录因子、蛋白质相互作用和核酸-蛋白质相互作用。因此，这些库可应用于寻找用于治疗和预防各种医疗状况的新药物。
• [EN] FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF<br/>[FR] MORPHOLINOPYRIMIDINES FUSIONNÉES ET PROCÉDÉS D'UTILISATION DE CES DERNIÈRES
  申请人：FORUM PHARMACEUTICALS INC

  公开号：WO2015138689A1

  公开（公告）日：2015-09-17

  The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.

  本公开涉及融合吗啉吡嘧啶，包含有效量融合吗啉吡嘧啶的药物组合物，以及在治疗神经退行性疾病中使用融合吗啉吡嘧啶的方法，包括向需要的受试者施用有效量的融合吗啉吡嘧啶。
• Intermediates for macrocyclic compounds
  申请人：Marsault Eric

  公开号：US09181298B2

  公开（公告）日：2015-11-10

  The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R1, R2, R3, R4, R5, R6, n1, m, p Z1, Z2, and Z3 are as describe in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.

  本发明涉及一种新型的大环化合物，其化学式为（I），以及其药用可接受的盐、水合物或溶剂化合物：其中R1、R2、R3、R4、R5、R6、n1、m、p、Z1、Z2和Z3如规范中所描述。该发明还涉及化合物的化学式（I），这些化合物是胃动素受体拮抗剂，可用于治疗与该受体相关的疾病以及与胃肠动力功能障碍相关的疾病。
• Continued Exploration of Trifunctional Alkyl 4-Chloro-2-diazo-3-oxobutanoates: Streamlined Entry into [1,2,3]Triazolo[5,1-c][1,4]benzoxazines and [1,2,3]Triazolo[5,1-c][1,4]benzoxazepines
  作者：Dmitry Dar’in、Mikhail Krasavin、Anton V. Budeev、Grigory Kantin

  DOI：10.1055/a-1348-9031

  日期：2021.6

  o-aminophenols followed by deprotection provided a convenient entry into [1,2,3]triazolo[5,1-c][1,4]benzoxazines, which are of high medicinal importance, as documented in the literature. The same approach applied to N-protected substituted o-(aminomethyl)phenols afforded [1,2,3]triazolo[5,1-c][1,4]benzoxazepines, which are practically unexplored compounds from a medicinal chemistry perspective. The syntheses

  进一步探索先前引入的4-氯-2-重氮-3-氧代丁酸烷基酯在与N保护的取代的邻氨基苯酚反应后进行脱保护的三功能特征，这为[1,2,3] triazolo [5， 1-c] [1,4]苯并恶嗪具有很高的医学重要性，如文献所记载。将相同的方法应用于N保护的取代邻-（氨基甲基）苯酚可提供[1,2,3]三唑并[5,1-c] [1,4]苯并x氮平，从医药化学的角度来看，它们实际上是未经探索的化合物。合成从苯酚的SN2型烷基化开始。除去保护基会触发亚胺的形成，然后合成Wolff 1,2,3-三唑。