4-氨基-5-氯-2-羟基苯甲酸甲酯 | 129511-06-4

• 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: 4-氨基-5-氯-2-羟基苯甲酸甲酯
• 英文名称: methyl 4-amino-5-chloro-2-hydroxybenzoate
• 英文别名: 4-amino-5-chloro-2-hydroxybenzoic acid,methyl ester
• CAS: 129511-06-4
• 化学式: C₈H₈ClNO₃
• 分子量: 201.609
• InChiKey: SXMFZXQWMHJMOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氨基-5-氯-2-羟基苯甲酸甲酯 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 6.5h， 生成 4-amino-5-chloro-2-prop-2-ynoxybenzoic acid
  参考文献：
  名称：

  Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation

  摘要：

  Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present a multidisciplinary lead discovery approach to identify and optimize small molecule inhibitors of pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA‐sequencing analysis, target validation experiments, and chemical absorption, distribution, metabolism, excretion and toxicity (ADMET)/pharmacokinetic (PK)/in vivo evaluation. The parallel synthesis employed for the production of the new benzamide derivatives enabled us to a) pinpoint key structural elements of the scaffold that provide potent fibroblast‐deactivating effects in cells, b) discriminate atoms or groups that favor or disfavor a desirable ADMET profile, and c) identify metabolic “hot spots”. Furthermore, we report the discovery of the first‐in‐class inhibitor leads for hypoxia up‐regulated protein 1 (HYOU1), a member of the heat shock protein 70 (HSP70) family often associated with cellular stress responses, particularly under hypoxic conditions. Targeting HYOU1 may therefore represent a potentially novel strategy to modulate fibroblast activation and treat chronic inflammatory and fibrotic disorders.

  DOI：

  10.1002/anie.202319157
• 作为产物：
  描述：

  4-amino-5-chloro-2-hydroxybenzoic acid 在 氯化亚砜 作用下， 以 甲醇 为溶剂， 生成 4-氨基-5-氯-2-羟基苯甲酸甲酯
  参考文献：
  名称：

  Substituted saturated and unsaturated indole quinoline and benzazepine

  摘要：

  披震胺类环酰胺化合物及其作为5-HT3拮抗剂的有价值用途被揭示，具有中枢神经系统和胃动力活性，且不具有任何D.sub.2受体结合特性。

  公开号：

  US04920219A1

文献信息

• Biphenyl compounds useful as muscarinic receptor antagonists
  申请人：Mammen Mathai

  公开号：US20050203139A1

  公开（公告）日：2005-09-15

  This invention provides compounds of formula I: wherein a, b, c, m, p, s, t, W, Ar 1 , X 1 , R 1 , R 2 , R 3 , R 4 , R 6 , and R 7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

  这项发明提供了公式I的化合物：其中a、b、c、m、p、s、t、W、Ar1、X1、R1、R2、R3、R4、R6和R7如规范中定义。公式I的化合物是肌氨酸受体拮抗剂。该发明还提供含有这些化合物的药物组合物，用于制备这些化合物的过程和中间体，以及使用这些化合物治疗肺部疾病的方法。
• Heterocyclic carboxylic acid amides and esters of azabicyclic compounds
  申请人：A. H. Robins Company, Incorporated

  公开号：US05190953A1

  公开（公告）日：1993-03-02

  Novel 1-azabicyclo[3.2.1]octan-5-ylmethyl and 1-azabicyclo[3.3.1]nonan-5-ylmethyl amines and alcohols are coupled with aryl carboxylic acids to obtain compounds having the formula: ##STR1## wherein X is --O-- or --NH-- and n is 1 or 2 which are useful in increasing gastric motility, in preventing emesis and emesis caused by anticancer treatments, anxiety, certain arrhythmias, and disorders caused by serotonin imbalances.

  小说1-azabicyclo [3.2.1]octan-5-ylmethyl和1-azabicyclo [3.3.1]nonan-5-ylmethyl胺和醇与芳香族羧酸偶联，获得具有以下公式的化合物：##STR1##其中X为--O--或--NH--，n为1或2，这些化合物在增加胃动力，预防抗癌治疗引起的呕吐和呕吐，焦虑，某些心律失常和由于血清素失衡引起的疾病方面有用。
• 2-substituted benzamide and benzoate derivatives of 3-aminoquinuclidine
  申请人：A. H. Robins Company, Incorporated

  公开号：US05236931A1

  公开（公告）日：1993-08-17

  This invention provides novel 3-quinuclidinyl benzamides and benzoates which have utility as therapeutical agents which exhibit anxiolytic, antipsychotic, cognition improvement, antiemetic and gastric prokinetic effects in warm blooded animals. The compounds useful in the methods and composition of this invention are represented by the formula: ##STR1## where X is oxygen or sulfur; Y is --NH or --O--; when Y is --O--, R.sup.1 is ##STR2## and when Y is --NH, R.sup.1 is ##STR3## and R.sup.2 is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl; the geometrical and optical isomers, or a pharmaceutically acceptable salt thereof.

  本发明提供了新型的3-喹诺啡啶基苯甲酰胺和苯甲酸酯，其具有作为治疗剂的实用性，可在温血动物中表现出抗焦虑、抗精神病、改善认知、抗恶心和胃动力作用。本发明方法和组合物中有用的化合物由以下式子表示：##STR1##其中 X 为氧或硫；Y 为--NH或--O--；当 Y 为--O--时，R1 为##STR2##当 Y 为--NH时，R1 为##STR3##且 R2 为氢、C1-C4烷基或C1-C4烯基；其几何和光学异构体，或其药学上可接受的盐。
• Carbocyclic carboxylic acid amides and esters of azabicyclic compounds
  申请人：A. H. Robins Company, Incorporated

  公开号：US05244907A1

  公开（公告）日：1993-09-14

  Novel 1-azabicyclo[3.2.1]octan-5-ylmethyl and 1-azabicyclo[3.3.1]nonan-5-ylmethyl amines and alcohols are coupled with aryl carboxylic acids to obtain compounds having the formula: ##STR1## wherein X is --O-- or --NH-- and n is 1 or 2 which are useful in increasing gastric motility, in preventing emesis and emesis caused by anticancer treatments, anxiety, certain arrhythmias, and disorders caused by serotonin imbalances.

  小说1-azabicyclo[3.2.1]octan-5-ylmethyl和1-azabicyclo[3.3.1]nonan-5-ylmethyl胺和醇与芳香族羧酸偶联，得到具有以下式子的化合物：##STR1## 其中X为--O--或--NH--，n为1或2，这些化合物有助于增加胃动力，预防由抗癌治疗、焦虑、某些心律失常和由血清素失衡引起的疾病引起的呕吐和呕吐。
• 3-[N-aroyl(or thioaroyl)aminomethyl]-3-quinuclidinols
  申请人：A. H. Robins Company, Incorporated

  公开号：US05137895A1

  公开（公告）日：1992-08-11

  3-[N-Aroyl(or thioaryol)aminoalkyl]-3-quinuclidinols corresponding to the formula: ##STR1## wherein X is O or S, and Ar is phenyl, substituted phenyl, indole, indazole or pyrimidine; optical isomers and the pharmaceutically acceptable acid addition salts and solvates thereof. These compounds have gastric emptying, antiemetic, anxiolytic and selective serotonin modulating or inhibiting activity.

  3-[N-Aroyl（或thioaryol）aminoalkyl]-3-quinuclidinols对应的公式如下：##STR1##其中X为O或S，Ar为苯基，取代苯基，吲哚，吲哚咪唑或嘧啶；其光学异构体和药学上可接受的酸盐和溶剂化物。这些化合物具有胃排空、抗恶心、抗焦虑和选择性血清素调节或抑制活性。