4-(5-(4-bromophenyl)-3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid | 361167-98-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(5-(4-bromophenyl)-3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid
• 英文别名: 4-[3-(4-bromophenyl)-5-(6-chloro-2-oxo-4-phenyl-1H-quinolin-3-yl)-3,4-dihydropyrazol-2-yl]-4-oxobutanoic acid
• CAS: 361167-98-8
• 化学式: C₂₈H₂₁BrClN₃O₄
• 分子量: 578.849
• InChiKey: XMGDSIFIWYIZOF-UHFFFAOYSA-N

物化性质

• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲醇 、 4-(5-(4-bromophenyl)-3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid 在 乙酰氯 作用下， 以 四氢呋喃 、 水 为溶剂， 以24%的产率得到methyl 4-(5-(4-bromophenyl)-3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate
  参考文献：
  名称：

  [EN] PYRAZOLINE DIHYDROQUINOLONES, PHARMACEUTICAL COMPOSITIONS, AND USES
  [FR] PYRAZOLINE DIHYDROQUINOLONES, COMPOSITIONS PHARMACEUTIQUES ET UTILISATIONS

  摘要：

  这一披露涉及吡唑啉二氢喹啉衍生物、药物组合物和用途。在某些实施例中，这些化合物是选择性NMDA受体抑制剂，并且在相关的治疗方法中具有用途。在某些实施例中，这一披露涉及包含以下式的化合物的药物组合物：式（I）或其盐、酯或前药。

  公开号：

  WO2014210456A1
• 作为产物：
  描述：

  (E)-3-(3-(4-bromophenyl)acryloyl)-6-chloro-4-phenylquinolin-2(1H)-one 在 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.5h， 生成 4-(5-(4-bromophenyl)-3-(6-chloro-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid
  参考文献：
  名称：

  Synthetic Lethality in Pancreatic Cancer: Discovery of a New RAD51-BRCA2 Small Molecule Disruptor That Inhibits Homologous Recombination and Synergizes with Olaparib

  摘要：

  Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example is the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on the possibility of triggering synthetic lethality using only small organic molecules (dubbed "fully small-molecule-induced synthetic lethality"). We exploited this paradigm to target pancreatic cancer, one of the major unmet needs in oncology. We discovered a dihydroquinolone pyrazoline-based molecule (35d) that disrupts the RAD51-BRCA2 protein-protein interaction, thus mimicking the effect of BRCA2 mutation. 35d inhibits the homologous recombination in a human pancreatic adenocarcinoma cell line. In addition, it synergizes with olaparib (a PARPi) to trigger synthetic lethality. This strategy aims to widen the use of PARPi in BRCA-competent and olaparib-resistant cancers, making fully small-molecule-induced synthetic lethality an innovative approach toward unmet oncological needs.

  DOI：

  10.1021/acs.jmedchem.9b01526

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF TUMORS<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE TUMEURS
  申请人：FONDAZIONE ST ITALIANO TECNOLOGIA

  公开号：WO2021116999A1

  公开（公告）日：2021-06-17

  The present invention relates to compounds of Formula (Ia) or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof. It further discloses a pharmaceutical composition comprising compounds of Formula (Ia) and the use of compounds of Formula (Ib), in particular for the use in the treatment of diseases or disorders wherein disrupting Rad51-BRCA2 interaction is beneficial.

  本发明涉及式(Ia)的化合物或药学上可接受的盐、水合物、溶剂合物、包合物、多晶型、立体异构体，还揭示了包含式(Ia)的化合物的药物组合物以及利用式(Ib)的化合物，特别是用于治疗破坏Rad51-BRCA2相互作用有益的疾病或紊乱的用途。
• [EN] PYRAZOLINE DIHYDROQUINOLONES, PHARMACEUTICAL COMPOSITIONS, AND USES<br/>[FR] PYRAZOLINE DIHYDROQUINOLONES, COMPOSITIONS PHARMACEUTIQUES ET UTILISATIONS
  申请人：UNIV EMORY

  公开号：WO2014210456A1

  公开（公告）日：2014-12-31

  This disclosure relates to pyrazoline dihydroquinolone derivatives, pharmaceutical compositions, and uses. In certain embodiments, the compounds are selective NMDA receptor inhibitors and are useful in therapeutic methods related thereto. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a compound of the following formula: Formula (I) or salts, esters, or prodrugs thereof, as provided herein.

  这一披露涉及吡唑啉二氢喹啉衍生物、药物组合物和用途。在某些实施例中，这些化合物是选择性NMDA受体抑制剂，并且在相关的治疗方法中具有用途。在某些实施例中，这一披露涉及包含以下式的化合物的药物组合物：式（I）或其盐、酯或前药。
• Subunit Selective NMDA Receptor Antagonists For The Treatment Of Neurological Conditions
  申请人：Traynelis Stephen F.

  公开号：US20110319416A1

  公开（公告）日：2011-12-29

  Provided are compounds, pharmaceutical compositions and methods of treating or preventing disorders associated with NMDA receptor activity, including schizophrenia, Parkinson's disease, cognitive disorders, depression, neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds of the general Formulas A-E, and pharmaceutically acceptable salts, esters, prodrugs or derivatives thereof are disclosed.
• Pyrazoline Dihydroquinolones, Pharmaceutical Compositions, and Uses
  申请人：EMORY UNIVERSITY

  公开号：US20160368897A1

  公开（公告）日：2016-12-22

  This disclosure relates to pyrazoline dihydroquinolone derivates, pharmaceutical compositions, and uses. In certain embodiments, the compounds are selective NMDA receptor inhibitors and are useful in therapeutic methods related thereto. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a compound of the following formula: Formula (I) or salts, esters, or prodrugs thereof, as provided herein.
• [EN] SUBUNIT SELECTIVE NMDA RECEPTOR ANTAGONISTS FOR THE TREATMENT OF NEUROLOGICAL CONDITIONS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR NMDA, SÉLECTIFS POUR DES SOUS-UNITÉS, ET DESTINÉS AU TRAITEMENT D'ÉTATS NEUROLOGIQUES
  申请人：UNIV EMORY

  公开号：WO2010088408A2

  公开（公告）日：2010-08-05

  Provided are compounds, pharmaceutical compositions and methods of treating or preventing disorders associated with NMDA receptor activity, including schizophrenia, Parkinson's disease, cognitive disorders, depression, neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds of the general Formulas A-E, and pharmaceutically acceptable salts, esters, prodrugs or derivatives thereof are disclosed.