4-(4-chlorophenyl)-3-[5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]quinolin-2(1H)-one | 1449373-56-1

• 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-(4-chlorophenyl)-3-[5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]quinolin-2(1H)-one
• 英文别名: 4-(4-chlorophenyl)-3-[5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-1H-quinolin-2-one
• CAS: 1449373-56-1
• 化学式: C₂₄H₁₇Cl₂N₃O
• 分子量: 434.324
• InChiKey: ZTRIXELJMVBFLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  53.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-chlorophenyl)-3-[5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]quinolin-2(1H)-one 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Development of a Dihydroquinoline–Pyrazoline GluN2C/2D-Selective Negative Allosteric Modulator of the N-Methyl-d-aspartate Receptor

  摘要：

  DOI：

  10.1021/acschemneuro.3c00181
• 作为产物：
  描述：

  2-氨基-N-甲氧基-N-甲基苯甲酰胺 在 盐酸 、 正丁基锂 、 一水合肼 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.08h， 生成 4-(4-chlorophenyl)-3-[5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]quinolin-2(1H)-one
  参考文献：
  名称：

  [EN] GLUN2C/D SUBUNIT SELECTIVE ANTAGONISTS OF THE N-METHYL-D-ASPARTATE RECEPTOR
  [FR] ANTAGONISTES SÉLECTIFS DES SOUS-UNITÉS GLUN2C/D DU RÉCEPTEUR N-MÉTHYL-D-ASPARTATE

  摘要：

  根据公式（I）提供的化合物或其盐或前药，以及包含该化合物的药物配方，用于治疗神经系统疾病。这些疾病可能包括提供神经保护、预防神经退化、治疗神经病性疼痛或治疗精神分裂症、精神病或抑郁症。此外，这些化合物可以与另一种活性成分结合使用。

  公开号：

  WO2019191424A1

文献信息

• [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。
• Structure–Activity Relationships and Pharmacophore Model of a Noncompetitive Pyrazoline Containing Class of GluN2C/GluN2D Selective Antagonists
  作者：Timothy M. Acker、Alpa Khatri、Katie M. Vance、Cathryn Slabber、John Bacsa、James P. Snyder、Stephen F. Traynelis、Dennis C. Liotta

  DOI：10.1021/jm400652r

  日期：2013.8.22

  Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors over GluN2A- and GluN2B-containing receptors. Several members of this class inhibit NMDA receptor responses in the nanomolar range and are more than 50-fold selective over GluN1/GluN2A and GluN1/GluN2B NMDA receptors, as well as AMPA, kainate, GABA, glycine, nicotinic, serotonin, and purinergic receptors. Analysis of the purified enantiomers of one of the more potent and selective compounds shows that the S-enantiomer is both more potent and more selective than the R-enantiomer. The S-enantiomer had an IC50 of 0.17-0.22 mu M at GluN2D- and GluN2C-containing receptors, respectively, and showed over 70-fold selectivity over other NMDA receptor subunits. The subunit selectivity of this class of compounds should be useful in defining the role of GluN2C- and GluN2D-containing receptors in specific brain circuits in both physiological and pathophysiological conditions.
• 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.
• GluN2C/D Subunit Selective Antagonists of the N-Methyl-D-Aspartate Receptor
  申请人：Emory University

  公开号：US20210017149A1

  公开（公告）日：2021-01-21

  A compound according to Formula (I) or salts or prodrugs thereof and pharmaceutical formulations comprising the compound are provided herein for the treatment of neurological disorders. The disorders may include providing neuroprotection, preventing neurodegeneration, treating neuropathic pain or treating schizophrenia, psychoses or depression. Furthermore, the compounds may be used in
• [EN] GLUN2 SUBUNIT SELECTIVE ANTAGONISTS OF THE N-METHYL-D-ASPARTATE RECEPTORS<br/>[FR] ANTAGONISTES SÉLECTIFS DE LA SOUS-UNITÉ GLUN2 DES RÉCEPTEURS DU N-MÉTHYL-D-ASPARTATE
  申请人：[en]EMORY UNIVERSITY

  公开号：WO2022226161A1

  公开（公告）日：2022-10-27

  Compounds that selectively inhibit the GluN2 subunits of NMDA receptors are disclosed. In general, the compounds have superior activity against GluN2C/D subunit(s) over GluN2A/B subunit(s). Optionally, the compounds have a structure of Formulas (I), (II), (III), or other formulas disclosed herein, enantiomers or diastereomers thereof, or pharmaceutically acceptable salts thereof. Pharmaceutical formulations containing one or more of the compounds are also disclosed. Additionally, methods of treating a neurological condition or disorder using the compounds or their pharmaceutical formulations thereof are disclosed. Exemplary neurological conditions or disorders include Parkinson's disease, dystonia and related motor disorders, depression, neuropsychiatric indications, stoke, hypoxia, traumatic brain injury, acute injuries involving the white matter, Alzheimer's disease, compulsivity and related disorders, and epilepsy.