3-氯-4,5-二羟基苯甲酸 | 87932-49-8

• 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: 3-氯-4,5-二羟基苯甲酸
• 英文名称: 3-chloro-4,5-dihydroxybenzoic acid
• 英文别名: 5-chloro-3,4-dihydroxybenzoic acid
• CAS: 87932-49-8
• 化学式: C₇H₅ClO₄
• mdl: MFCD01742816
• 分子量: 188.567
• InChiKey: GGUNECQLDCNDDY-UHFFFAOYSA-N

物化性质

• 沸点：
  391.7±42.0 °C(Predicted)
• 密度：
  1.702±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2918290000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-氯-4,5-二羟基苯甲酸 在 ammonium hydroxide 、 氯化亚砜 、 硫酸 、 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 4.33h， 生成 (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-ethoxyiminoacetyl]amino]-3-[[(3-chloro-4,5-dihydroxybenzoyl)amino]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Pharmacokinetics of catechol cephalosporins. The effect of incorporating substituents into the catechol moiety on pharmacokinetics in a marmoset model

  摘要：

  Two series of cephalosporins A and B have been synthesized, bearing at C-3' catechols substituted with various electron withdrawing groups (Y) and differing links (X), and were evaluated for their in vitro antibacterial activity and their pharmacokinetics in marmosets. Compounds in series A, bearing an isobutyric oxime substituent, proved to be highly active against Gram-negative organisms and were especially noteworthy for showing long elimination phase (beta) half-lives in marmosets. It was established that introduction of electron withdrawing substituents greatly increased the beta-half-lives of compounds (5, X = NHCO, Y = H, t1/2 = 1.25 h, AUC = 27 mg/h per L; 11, X = NHCO, Y = 5-Cl, t1/2, = 4.5 h, AUC = 638 mg/h per L) and that the nature of the link also influenced t1/2, the highest values being obtained when X = NHCO and OCO. Acidities (pK(a) values) of the substituted catechols were measured, and relationships between the acidities and half-lives were evaluated. Thus it was established that the more acidic catechols gave the longest half-lives (12, X = NHCO, Y = 2,5-Cl2, t1/2 = 8.2 h, AUC = 461 mg/h per L). Further elaboration of the catechol to bicyclic systems maintained good pharmacokinetics when the pK(a) was sufficiently acidic.

  DOI：

  10.1021/jm00092a015
• 作为产物：
  描述：

  5-氯香草酸 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以79%的产率得到3-氯-4,5-二羟基苯甲酸
  参考文献：
  名称：

  设计和合成一种有效的、高选择性的、口服生物可利用的视黄酸受体α激动剂

  摘要：

  基于配体的虚拟筛选练习检查了 AM 580 ( 2 ) 和 AGN 193836 ( 3 ) 可能的生物活性构象，用于鉴定新型亲脂性较低的 RARα 激动剂 4-(3,5-二氯-4-乙氧基苯甲酰胺基)苯甲酸5 ，对 RARβ 和 RARγ 受体具有良好的选择性。对模板5衍生物的 3,5-取代基的药物化学参数的分析使我们能够设计一类具有较低内在清除率和较高口服生物利用度的药物样分子，从而产生了新型 RARα 激动剂 4-(3-氯-4-乙氧基-5-异丙氧基苯甲酰胺基)-2-甲基苯甲酸56 ，在人类和小鼠 RAR 受体上具有高 RARα 效力和优异的选择性（相对于 RARβ（2 个数量级）和 RARγ（4 个数量级）），药物经过改进类属性。这种 RARα 特异性激动剂56在小鼠和狗中具有较高的口服生物利用度 (>80%)，具有良好的 PK 特性，并且在细胞毒性和基因毒性筛选中显示无活性。

  DOI：

  10.1016/j.bmc.2017.12.015

文献信息

• [EN] INSULIN ANALOGUES WITH GLUCOSE REGULATED CONFORMATIONAL SWITCH<br/>[FR] ANALOGUES DE L'INSULINE À COMMUTATEUR DE CONFORMATION RÉGULÉ PAR LE GLUCOSE
  申请人：THERMALIN INC

  公开号：WO2021022116A1

  公开（公告）日：2021-02-04

  The present invention relates to glucose-responsive insulin analogues, compositions including the glucose-responsive insulin analogues, and methods of lowering blood sugar of a patient using the insulin analogue or compositions thereof.

  本发明涉及葡萄糖响应胰岛素类似物，包括该葡萄糖响应胰岛素类似物的组合物，以及使用该胰岛素类似物或其组合物降低患者血糖的方法。
• MONOMERS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
  申请人：Barany Francis

  公开号：US20140194383A1

  公开（公告）日：2014-07-10

  Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

  本发明描述了在水中介质中与一个、两个、三个或更多其他单体接触时能够形成具有生物学用途的多聚体的单体。在一方面，这样的单体可能能够在水介质中（例如，体内）与另一个单体结合形成多聚体（例如，二聚体）。考虑的单体可能包括一个配体部分、一个连接元素和一个连接器元素，连接器元素连接配体部分和连接元素。在水介质中，这样的考虑单体可能通过每个连接元素相互连接，因此可能能够实质上同时调节一个或多个生物分子，例如，调节蛋白质上的两个或多个结合域，或者调节不同蛋白质上的结合域。
• [EN] THERAPEUTIC ARYL-AM I DO-ARYL COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS ARYLAMIDOARYLIQUES THÉRAPEUTIQUES ET LEUR UTILISATION
  申请人：KING S COLLEGE LONDON

  公开号：WO2011027106A1

  公开（公告）日：2011-03-10

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as "AAA compounds"), which, inter alia, are (selective) retinoic acid receptor α (RARα) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARα, and in the treatment of diseases and conditions that are mediated by RARα, that are ameliorated by the activation of RARα, etc., including cognitive disorders, memory impairment, memory deficit, senile dementia, Alzheimer's disease, early stage Alzheimer's disease, intermediate stage Alzheimer's disease, late stage Alzheimer's disease, cognitive impairment, and mild cognitive impairment.

  本发明一般涉及治疗化合物领域，更具体地涉及以下结构的某些芳基酰胺-芳基化合物（为方便起见，统称为“AAA化合物”），这些化合物是（选择性的）视黄酸受体α（RARα）激动剂。本发明还涉及包含这种化合物的药物组合物，以及利用这种化合物和组合物在体内外（选择性地）激活RARα，并用于治疗由RARα介导的疾病和症状，通过激活RARα得到改善等方面，包括认知障碍、记忆障碍、记忆缺陷、老年痴呆症、阿尔茨海默病、早期阿尔茨海默病、中期阿尔茨海默病、晚期阿尔茨海默病、认知障碍和轻度认知障碍的治疗。
• Therapeutic Aryl-Amido-Aryl Compounds and Their Use
  申请人：Corcoran Jonathan Patrick Thomas

  公开号：US20120149737A1

  公开（公告）日：2012-06-14

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-amido-aryl compounds of the following formula (for convenience, collectively referred to herein as “AAA compounds”), which, inter alia, are (selective) retinoic acid receptor α (RARα) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARα, and in the treatment of diseases and conditions that are mediated by RARα, that are ameliorated by the activation of RARα, etc., including cognitive disorders, memory impairment, memory deficit, senile dementia, Alzheimer's disease, early stage Alzheimer's disease, intermediate stage Alzheimer's disease, late stage Alzheimer's disease, cognitive impairment, and mild cognitive impairment.

  本发明涉及治疗化合物领域，更具体地涉及以下公式的某些芳基酰胺-芳基化合物（为方便起见，以下统称为“AAA化合物”），其为（选择性）视黄酸受体α（RARα）激动剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体外和体内（选择性地）激活RARα，并用于治疗由RARα介导的疾病和症状，以及通过激活RARα改善的疾病和症状，包括认知障碍、记忆障碍、记忆缺陷、老年性痴呆、阿尔茨海默病、早期阿尔茨海默病、中期阿尔茨海默病、晚期阿尔茨海默病、认知损害和轻度认知损害。
• Cephalosporin compounds and their use
  申请人：Ishimaru, Toshiyasu

  公开号：EP0400805A1

  公开（公告）日：1990-12-05

  A cephalosporin compound of the formula (I): wherein X and Y may be the same or different and are a hydrogen or halogen atom; Z is a hydrogen or halogen atom, -CH=CH₂, -CH=CH-CH₃, -OR¹, -SR² or -CH₂W in which R¹ and R² are a lower alkyl group and W is a hydrogen atom or a nucleophilic residue, its pharmaceutically acceptable salt, a process for preparing the same and their antibacterial composition.

  一种头孢菌素化合物，其化学式为（I）：其中X和Y可能相同或不同，为氢原子或卤素原子；Z为氢原子或卤素原子，-CH=CH₂，-CH=CH-CH₃，-OR¹，-SR²或-CH₂W，其中R¹和R²为较低的烷基基团，W为氢原子或亲核残基，以及其药用可接受盐、制备方法及其抗菌组合物。