4-Methoxy-6,6-dimethyl-5-[2-oxo-2-(3,4,5-trimethoxyphenyl)ethyl]-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-6-ium

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-Methoxy-6,6-dimethyl-5-[2-oxo-2-(3,4,5-trimethoxyphenyl)ethyl]-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-6-ium
• 英文别名: 2-(4-methoxy-6,6-dimethyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-6-ium-5-yl)-1-(3,4,5-trimethoxyphenyl)ethanone
• 化学式: C24H30NO7+
• 分子量: 444.5
• InChiKey: GKBZWIFQAGWDFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

文献信息

• Method for inhibiting growth of cancer cells
  申请人：Pain Therapeutics, Inc.

  公开号：US10363239B2

  公开（公告）日：2019-07-30

  A method of inhibiting the growth of cancer cells is disclosed in which cancer cells that contain an enhanced amount relative to non-cancerous cells of one or more of phosphorylated mTOR, Akt1, ERK2 and serine2152-phosphorylated filamin A are contacted with an FLNA-binding effective amount of a compound or a pharmaceutically acceptable salt thereof that binds to the pentapeptide of filamin A (FLNA) of SEQ ID NO: 1 and exhibits at least about 60 percent of the FITC-labeled naloxone binding amount when present at a 10 μM concentration and using unlabeled naloxone as the control inhibitor at the same concentration. A compound that binds to the FLNA pentapeptide preferably also contains at least four of the six pharmacophores of FIGS. 19-24.

  本发明公开了一种抑制癌细胞生长的方法，该方法是将含有磷酸化的 mTOR、Akt1、ERK2 和丝氨酸 2152 磷酸化的丝胺 A 中的一种或多种含量相对于非癌细胞有所增加的癌细胞，与 FLNA 结合有效量的化合物或其药学上可接受的盐接触，该化合物或其药学上可接受的盐与 SEQ ID NO：1的五肽（FLNA）结合的化合物或其药学上可接受的盐，并且在10 μM浓度下，以相同浓度的未标记纳洛酮作为对照抑制剂时，显示出至少约60％的FITC标记纳洛酮结合量。与 FLNA 五肽结合的化合物最好还含有图 19-24 中六种药效团中的至少四种。
• Method of inhibiting tau phosphorylation
  申请人：Pain Therapeutics, Inc.

  公开号：US10760052B2

  公开（公告）日：2020-09-01

  A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

  本发明公开了一种抑制 tau 蛋白磷酸化和/或 TLR4 介导的免疫反应的方法。该方法考虑向有公认需要的细胞如中枢神经系统细胞施用有效量的化合物或其药学上可接受的盐，该化合物或其药学上可接受的盐与 SEQ ID NO: 1 的丝胺 A (FLNA) 五肽结合，并包含图 35-40 六种药效团中的至少四种。
• METHOD OF INHIBITING TAU PHOSPHORYLATION
  申请人：Pain Therapeutics, Inc.

  公开号：US20190136184A1

  公开（公告）日：2019-05-09

  A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35 - 40.
• Alzheimer's Disease Assay in a Living Patient
  申请人：Pain Therapeutics, Inc.

  公开号：US20210389298A1

  公开（公告）日：2021-12-16

  An assay for Alzheimer's disease pathology (AD) in a living patient is disclosed wherein an amount of α7nAChR or TLR4 in a FLNA-captured protein complex or α7nAChR in an Aβ-captured protein complex or α7nAChR-FLNA, TLR4-FLNA and/or α7nAChR-Aβ 42 complex present as a protein-protein complex in a sample is determined and compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is determined and compared to an amount determined in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four of the six pharmacophores of FIGS. 7 - 12 . An amount of protein or protein complex determined in the presence of the medicament less than the first determined amount indicates a favorable treatment prognosis.