NSC366140无结构图 | 99009-20-8

• 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
• 中文名称: NSC366140无结构图
• 中文别名: NSC 366140 无结构图
• 英文名称: Pyrazoloacridine
• 英文别名: PZA；9-methoxy-N,N-dimethyl-5-nitropyrazolo[3,4,5-kl]acridine-2(6H)-propanamine；3-(4-methoxy-10-nitro-8,14,15-triazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2(7),3,5,9,11,13(16)-heptaen-14-yl)-N,N-dimethylpropan-1-amine
• CAS: 99009-20-8
• 化学式: C₁₉H₂₁N₅O₃
• 分子量: 367.407
• InChiKey: HZCWPKGYTCJSEB-UHFFFAOYSA-N

物化性质

• 沸点：
  584.3±50.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  Water > 10.12 (mg/mL)
• 稳定性/保质期：
  Bulk: Test samples stored for 3 months at 25 °C and 50 °C under light and dark conditions showed no degradation (HPLC). Solution: Aqueous solutions 2 mg/mL) showed no degradation after 48 hr at 25 °C.

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

吡唑洛吖啶已知的人体代谢物包括N-去甲基吡唑洛吖啶。

Pyrazoloacridine has known human metabolites that include N-DEMETHYL Pyrazoloacridine.

来源:NORMAN Suspect List Exchange

制备方法与用途

生物活性

Pyrazoloacridine (NSC 366140) 具有抗癌活性，能够抑制拓扑异构酶 1 和 2 的活性。在 K562 髓系白血病细胞中，其 IC50 值为 1.25 μM（24 小时）。

体外研究

• Pyrazoloacridine (NSC 366140, PD 115934) 对有氧和缺氧 HCT-8 细胞的 IC50 值分别为 10.7 μM 和 4.5 μM。
• 在体外，Pyrazoloacridine (NSC 366140, 2-4 μM) 能够阻断拓扑异构酶 I 和 II 的催化活性。
• Pyrazoloacridine (NSC 366140) 对顺铂和紫杉醇耐药的卵巢癌表现出活性。
• 在 MCF-7 乳腺癌细胞中，Pyrazoloacridine (NSC 366140) 导致延迟 DNA 碎片化。
• Pyrazoloacridine (NSC 366140) 能够诱导 P53 缺失的 Hep 3B 人类肝癌细胞凋亡。

细胞毒性测定

细胞系	K562 粒细胞白血病细胞
浓度	0-500 μM
培养时间	1 小时或 24 小时
结果	- 当 K562 细胞在 PA 中孵育 1 小时后移至软琼脂中，观察到 IC50 约为 -50 μM。相反，在细胞与 PA 孵育 24 小时后，IC50 降至 1.25 μM。

请注意，文中“-50 μM”的表述可能存在误植或误译，正确的 IC50 值应为 1.25 μM（参照原文）。

反应信息

• 作为产物：
  描述：

  2,6-二氯-3-硝基苯甲酸 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 43.5h， 生成 NSC366140无结构图
  参考文献：
  名称：

  2-(Aminoalkyl)-5-nitropyrazolo[3,4,5-kl]acridines, a new class of anticancer agents

  摘要：

  2-(Aminoalkyl)-5-nitropyrazolo[3,4,5-kl]acridines were prepared from substituted anilines via the 1-chloro-4-nitroacridones followed by condensation with [(alkylamino)alkyl]hydrazines. Impressive activity was demonstrated for the 9-hydroxy, 9-alkoxy, and 9-acyloxy analogs in vitro on a L1210 leukemia line and in vivo against the P388 leukemia. Advanced studies led to the selection of 3bbb for clinical trial.

  DOI：

  10.1021/jm00104a001

文献信息

• J. Med. Chem. 1992, 35, 4770-4778
  作者：

  DOI：——

  日期：——
• Capps David B., Dundar James, Kesten Suzanne R., Shillis Joan, Werbel Les+, J. Med. Chem., 35 (1992) N 26, S 4770-4778
  作者：Capps David B., Dundar James, Kesten Suzanne R., Shillis Joan, Werbel Les+

  DOI：——

  日期：——
• Pyrazolo(3,4,5-kl)acridine compounds, pharmaceutical compositions comprising the same and processes for their production
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0138302B1

  公开（公告）日：1988-03-09
• Solid forms of anti-egfr antibodies
  申请人：Matheus Susanne

  公开号：US20070122411A1

  公开（公告）日：2007-05-31

  The invention relates to solid forms of antibodies against the EGF receptor, in particular precipitates and crystals of monoclonal antibodies against the EGF receptor, particularly preferably of Mab C225 (cetuximab) and Mab h425 (EMD 72000), which result in biologically active antibody protein through dissolution or suspension in aqueous medium, obtainable by precipitation of the antibody and/or one of its variants and/or fragments dissolved or suspended in aqueous medium by means of a precipitation reagent. The invention furthermore relates to pharmaceutical preparations comprising at least one solid form of above-mentioned antibodies in precipitated non-crystalline, precipitated crystalline or in soluble or suspended form, and optionally excipients and/or adjuvants and/or further pharmaceutical active ingredients, and to a process for the preparation of solid forms of anti-EGFR antibodies according to the invention.
• Highly concentrated, liquid formulations of anti-egfr antibodies
  申请人：Matheus Susanne

  公开号：US20070172475A1

  公开（公告）日：2007-07-26

  The invention relates to processes for the preparation of highly concentrated, liquid formulations comprising at least one anti-EGFR antibody and/or one of its variants and/or fragments, in particular monoclonal antibodies against the EGF receptor, particularly preferably of Mab C225 (cetuximab) and Mab h425 (EMD 72000), by ultrafiltration. The invention furthermore relates to highly concentrated, liquid formulations of anti-EGFR antibodies, in particular of monoclonal antibodies against the EGF receptor, particularly preferably Mab C225 (cetuximab) and Mab h425 (EMD 72000) and/or variants and/or fragments thereof, characterised in that the highly concentrated, liquid formulations have a content of anti-EGFR antibodies of 10-250, preferably 50-180 mg/ml, particularly preferably of 100-150 mg/ml, and to the use thereof.