N-(3,5-bis(trifluoromethyl)phenyl)-3-chloro-2-hydroxybenzamide | 634184-93-3

• 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: N-(3,5-bis(trifluoromethyl)phenyl)-3-chloro-2-hydroxybenzamide
• 英文别名: N-[3,5-Bis(trifluoromethyl)phenyl]-3-chloro-2-hydroxybenzamide；N-[3,5-bis(trifluoromethyl)phenyl]-3-chloro-2-hydroxybenzamide
• CAS: 634184-93-3
• 化学式: C₁₅H₈ClF₆NO₂
• 分子量: 383.677
• InChiKey: MIFXBNFNNPOWOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氯水杨酸 、 间二(三氟甲基)苯胺 在 三氯化磷 作用下， 以 甲苯 为溶剂， 以24%的产率得到N-(3,5-bis(trifluoromethyl)phenyl)-3-chloro-2-hydroxybenzamide
  参考文献：
  名称：

  IMD-0354 的结构功能研究鉴定出高活性粘菌素佐剂。

  摘要：

  由多重耐药（MDR）细菌，特别是革兰氏阴性菌引起的感染是一个不断升级的全球健康威胁。临床医生常常被迫使用最后手段抗生素粘菌素。然而，粘菌素耐药性正变得越来越普遍，导致可能出现多重耐药革兰氏阴性菌感染没有治疗选择的情况。开发规避细菌耐药机制的佐剂是开发新抗生素的一种有前途的正交方法。我们最近披露，已知的 IKK-β 抑制剂 IMD-0354 可有效抑制几种革兰氏阴性菌株的粘菌素耐药性。在这项研究中，我们探索了 IMD-0354 支架与粘菌素耐药性抑制之间的构效关系 (SAR)，并鉴定了几种比母体对鲍曼不动杆菌和肺炎克雷伯菌高度粘菌素耐药菌株具有更有效活性的化合物。

  DOI：

  10.1002/cmdc.201900560

文献信息

• 2-HYDROXYARYLAMIDE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：Korea Research Institute of Bioscience and Biotechnology

  公开号：US20140221411A1

  公开（公告）日：2014-08-07

  The present invention relates to a 2-hydroxyarylamide derivative or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition for preventing or treating cancer comprising the same as an active ingredient. The 2-hydroxyarylamide derivative prepared by the present invention is excellent in the inhibition of the activity of TMPRSS4 serine protease and the suppression of the infiltration of TMPRSS4-expressed cancer cells, and thus can be useful as a composition for preventing or treating cancer by inhibiting TMPRSS4 over-expressed in cancer cells, particularly, colorectal cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, or stomach cancer cells.

  本发明涉及一种2-羟基芳酰胺衍生物或其药用可接受的盐，其制备方法，以及作为活性成分的预防或治疗癌症的药物组合物。本发明制备的2-羟基芳酰胺衍生物在抑制TMPRSS4丝氨酸蛋白酶的活性和抑制TMPRSS4表达的癌细胞浸润方面表现出色，因此可以作为一种通过抑制癌细胞中TMPRSS4过度表达的组合物，特别是结肠癌、肺癌、乳腺癌、前列腺癌、卵巢癌、胰腺癌或胃癌细胞的预防或治疗癌症的组合物。
• [EN] COMPOUNDS AND METHODS FOR POTENTIATING COLISTIN ACTIVITY<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR POTENTIALISER L'ACTIVITÉ DE LA COLISTINE
  申请人：UNIV NOTRE DAME DU LAC

  公开号：WO2021086567A1

  公开（公告）日：2021-05-06

  Infections caused by multidrug-resistant (MDR) bacteria, particularly Gram-negative bacteria, are an escalating global health threat. Often clinicians are forced to administer the last resort antibiotic colistin, however colistin resistance is becoming increasingly prevalent, giving rise to the potential for a situation in which there are no treatment options for MDR Gram-negative infections. The development of adjuvants that circumvent bacterial resistance mechanisms is a promising orthogonal approach to the development of new antibiotics. We recently disclosed that the known IKK-β inhibitor IMD-0354 potently suppresses colistin resistance in several Gram-negative strains. In this disclosure, we explore the structure activity relationship (SAR) between the IMD-0354 scaffold and colistin resistance suppression, and identify several compounds with more potent activity than the parent against highly colistin resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae.

  由多药耐药（MDR）细菌引起的感染，特别是革兰氏阴性细菌，是一种不断加剧的全球健康威胁。通常情况下，临床医生被迫使用最后的抗生素科利星，然而科利星耐荐性越来越普遍，导致可能出现无法治疗MDR革兰氏阴性细菌感染的情况。开发能够规避细菌耐药机制的辅助剂是开发新抗生素的一种有前途的正交方法。我们最近披露，已知的IKK-β抑制剂IMD-0354能够有效抑制几种革兰氏阴性菌株对科利星的耐药性。在这一披露中，我们探讨了IMD-0354骨架与科利星耐药抑制之间的结构活性关系（SAR），并确定了几种比母体更具有强效活性的化合物，对鲍曼不动杆菌和肺炎克雷伯氏菌高度耐科利星的菌株具有更强的活性。
• Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors
  作者：Sunghyun Kang、Hye-Jin Min、Min-Seo Kang、Myung-Geun Jung、Semi Kim

  DOI：10.1016/j.bmcl.2013.01.055

  日期：2013.3

  TMPRSS4 is a novel type II transmembrane serine protease that has been implicated in the invasion and metastasis of colon cancer cells. In this study, a novel series of 2-hydroxydiarylamide derivatives were synthesized and evaluated for inhibiting TMPRSS4 serine protease activity and suppressing cancer cell invasion. These derivatives demonstrated good inhibitory activity against TMPRSS4 serine protease, which correlated with the promising anti-invasive activity of colon cancer cells overexpressing TMPRSS4. (C) 2013 Elsevier Ltd. All rights reserved.
• Discovery and Structure Relationships of Salicylanilide Derivatives as Potent, Non-acidic P2X1 Receptor Antagonists
  作者：Maoqun Tian、Aliaa Abdelrahman、Younis Baqi、Eduardo Fuentes、Djamil Azazna、Claudia Spanier、Sabrina Densborn、Sonja Hinz、Ralf Schmid、Christa E. Müller

  DOI：10.1021/acs.jmedchem.0c00435

  日期：2020.6.11

  Antagonists for the ATP-gated ion channel receptor P2X1 have potential as antithrombotics and for treating hyperactive bladder and inflammation. In this study, salicylanilide derivatives were synthesized based on a screening hit. P2X1 antagonistic potency was assessed in 1321N1 astrocytoma cells stably transfected with the human P2X1 receptor by measuring inhibition of the ATP-induced calcium influx. Structure-activity relationships were analyzed, and selectivity versus other P2X receptor subtypes was assessed. The most potent compounds, N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (1, IC50 0.0192 mu M) and N-[3,5-bis(trifluoromethyl)phenyl]-4-chloro-2-hydroxybenzamide (14, IC50 0.0231 mu M), displayed >500-fold selectivity versus P2X2 and P2X3, and 10-fold selectivity versus P2X4 and P2X7 receptors, and inhibited collagen-induced platelet aggregation. They behaved as negative allosteric modulators, and molecular modeling studies suggested an extracellular binding site. Besides selective P2X1 antagonists, compounds with ancillary P2X4 and/or P2X7 receptor inhibition were discovered. These compounds represent the first potent, non-acidic, allosteric P2X1 receptor antagonists reported to date.
• PROPHYLACTIC OR THERAPEUTIC AGENT FOR PULMONARY HYPERTENSION COMPRISING UNSATURATED 5-MEMBERED HETEROCYCLE-CONTAINING COMPOUND
  申请人：TOHOKU UNIVERSITY

  公开号：US20210299093A1

  公开（公告）日：2021-09-30

  The present invention provides a preventive or therapeutic agent for pulmonary hypertension, including a compound represented by the following formula (I) or a salt thereof: where: -A- represents —NH—, —S—, or —O—; R 1 and R 2 are identical to or different from each other, and each represent a hydrogen atom or an alkyl group; R 3 represents a hydrogen atom, a halogen atom, or an alkyl group; R 4 represents a hydrogen atom or an alkyl group; R 5 represents a hydrogen atom or an alkyl group; R 6 and R 7 are identical to or different each other, and each represent a hydrogen atom, a halogen atom, or an alkyl group; and R 6 and R 7 may form an unsaturated hydrocarbon six-membered ring together with a carbon atom to which R 6 is bonded and a carbon atom to which R 7 is bonded.