3,5-二氯-2-羟基苯甲酰氯 | 39614-80-7

• 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: 3,5-二氯-2-羟基苯甲酰氯
• 英文名称: 3,5-dichloro-2-hydroxy-benzoyl chloride
• 英文别名: 3,5-Dichloro-2-hydroxybenzoyl chloride
• CAS: 39614-80-7
• 化学式: C₇H₃Cl₃O₂
• 分子量: 225.459
• InChiKey: NMRFTQSCAAZYSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-二氯-2-羟基苯甲酰氯 在 Ammonium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以23%的产率得到3,5-二氯-2-羟基苯甲酰胺
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Modified Salicylanilides as Cell Permeable Inhibitors of Poly(ADP-ribose) Glycohydrolase (PARG)

  摘要：

  The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials because of their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, target-related affinity profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of druglike compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogues of one of the most active chemotypes were synthesized to explore the structure activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1 and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development.

  DOI：

  10.1021/jm200325s
• 作为产物：
  描述：

  3,5-二溴-2-羟基苯甲酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 3,5-二氯-2-羟基苯甲酰氯
  参考文献：
  名称：

  Design, Synthesis, and Biological Activities of Closantel Analogues: Structural Promiscuity and Its Impact on Onchocerca volvulus

  摘要：

  Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3 molting was investigated. Structure activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.

  DOI：

  10.1021/jm200364n

文献信息

• Nitrogen-containing fused ring compounds and use thereof
  申请人：Hirata Kazuyuki

  公开号：US20070010670A1

  公开（公告）日：2007-01-11

  A URAT1 activity inhibitor containing a nitrogen-containing fused ring compound represented by the following formula [1]: wherein each symbol is as defined in the description. The present invention is useful for the prophylaxis or treatment of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like.

  一种包含氮含有融合环化合物的URAT1活性抑制剂，其化学式如下所示[1]： 其中每个符号如描述中所定义。本发明对于预防或治疗显示尿酸参与的病理学，如高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等方面具有用处。
• Pharmaceutical Compositions Comprising Nitrogen-Containing Fused Ring Coumpounds
  申请人：Miki Kazuki

  公开号：US20080305169A1

  公开（公告）日：2008-12-11

  [Problems] The present invention provides pharmaceutical composition which is effective for the prophylaxis or treatment of pathology showing involvement of uric acid (hyperuricemia, gouty tophus, acute gout arthritis, chronic gout arthritis, gouty kidney, urolithiasis, renal function disorder, coronary arterial disease, ischemic heart disease and the like) and the like, and is superior in the time-course stability and dissolution property (disintegration property). [Solving Means] The pharmaceutical composition of the present invention is a pharmaceutical composition comprising a nitrogen-containing fused ring compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable additives, wherein the nitrogen-containing fused ring compound or a pharmaceutically acceptable salt thereof is not in contact with a basic additive: wherein each symbol is as described in the specification.

  本发明提供了一种药物组合物，用于预防或治疗涉及尿酸的病理（高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等），并且在时间稳定性和溶解性（分解性）方面具有优越性。 【解决手段】本发明的药物组合物是一种药物组合物，包括下式【1】所表示的含氮融合环化合物或其药学上可接受的盐，以及一种或多种药学上可接受的添加剂，其中所述的含氮融合环化合物或其药学上可接受的盐与碱性添加剂不接触： 其中每个符号如说明书中所述。
• Production Method of Nitrogen-Containing Fused Ring Compounds
  申请人：Hirata Kazuyuki

  公开号：US20080064871A1

  公开（公告）日：2008-03-13

  [Problems] The present invention provides a superior production method and a superior purification method of compounds effective for the treatment or prophylaxis of pathology showing involvement of uric acid, such as hyperuricemia, gouty tophus, acute gouty arthritis, chronic gouty arthritis, gouty kidney, urolithiasis, renal function disorder, coronary artery disease, ischemic heart disease and the like. [Means] A compound represented by the following formula [2] or a pharmaceutically acceptable salt thereof can be produced by reacting a compound represented by the following formula [3] or a salt thereof with a compound represented by the following formula [4], a salt thereof or a reactive derivative thereof. Moreover, crystallization of a compound represented by the formula [2] can be performed with industrially superior workability, and high quality crystals of a compound represented by the formula [2] can be obtained. wherein each symbol is as defined in the description.

  本发明提供了一种优越的化合物生产方法和优越的纯化方法，用于治疗或预防涉及尿酸的病理学，如高尿酸血症、痛风石、急性痛风性关节炎、慢性痛风性关节炎、痛风性肾脏、尿路结石、肾功能障碍、冠状动脉疾病、缺血性心脏病等。 [手段] 通过将以下式[3]所代表的化合物或其盐与以下式[4]所代表的化合物、其盐或其反应衍生物反应，可以制备以下式[2]所代表的化合物或其药用可接受的盐。此外，可以以工业上优越的可操作性进行以下式[2]所代表的化合物的结晶，并且可以获得以下式[2]所代表的化合物的高质量晶体。 其中每个符号如描述中所定义。
• Scaffold Diversity Inspired by the Natural Product Evodiamine: Discovery of Highly Potent and Multitargeting Antitumor Agents
  作者：Shengzheng Wang、Kun Fang、Guoqiang Dong、Shuqiang Chen、Na Liu、Zhenyuan Miao、Jianzhong Yao、Jian Li、Wannian Zhang、Chunquan Sheng

  DOI：10.1021/acs.jmedchem.5b00910

  日期：2015.8.27

  thio-evodiamine (66c) showed excellent in vitro and in vivo antitumor efficacy with good tolerability and low toxicity. Antitumor mechanism and target profiling studies indicate that compound 66c is the first-in-class triple topoisomerase I/topoisomerase II/tubulin inhibitor. Overall, this study provided an effective strategy for natural product-based drug discovery.

  基于天然产物的药物发现中的一个关键问题是如何将产物转化为具有最佳药理特性的类药物分子。天然产物启发的支架多样性的产生是一种有效但具有挑战性的策略，用于研究更广阔的化学空间并确定有前途的药物线索。将我们的工作扩展到天然产物evodiamine，设计并合成了一个包含11个evodiamine启发的新型支架及其衍生物的多样化文库。它们中的大多数显示出对各种人类癌细胞系的良好至优异的抗肿瘤活性。特别地，3-氯-10-羟基硫代吴茱萸碱（66C）显示出优异的体外和体内抗肿瘤功效，耐受性好，毒性低。抗肿瘤机制和靶标分析研究表明，化合物66c是同类中的第一个三重拓扑异构酶I /拓扑异构酶II /微管蛋白抑制剂。总的来说，这项研究为基于天然产物的药物发现提供了有效的策略。
• Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase
  作者：Yaya Liu、Pamela L. Donner、John K. Pratt、Wen W. Jiang、Teresa Ng、Vijaya Gracias、Steve Baumeister、Paul E. Wiedeman、Linda Traphagen、Usha Warrior、Clarence Maring、Warren M. Kati、Stevan W. Djuric、Akhteruzzaman Molla

  DOI：10.1016/j.bmcl.2008.04.068

  日期：2008.6

  elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.

  卤水杨酰胺衍生物通过高通量筛选被鉴定为 HCV NS5B 聚合酶的有效抑制剂。随后的结构和活性关系揭示了水杨酰胺部分对最佳活性的绝对要求。水杨酰胺部分的羟基或酰胺基团的甲基化消除了活性，而两个苯环上的取代是可接受的。卤代水杨酰胺衍生物在延伸核苷酸方面显示出非竞争性，并显示出针对基因型 1-3 HCV NS5B 聚合酶的广泛基因型活性。抑制剂竞争研究表明与噻二嗪类化合物占据的起始口袋的加性结合模式和由二酮酸占据的延伸口袋的加性结合模式，但是对于被苯并咪唑类抑制剂占据的变构拇指口袋而言，这是一种相互排斥的结合模式。因此，卤代水杨酰胺代表了一类新型的 HCV NS5B 聚合酶变构抑制剂。