NSC 177223 | 36707-00-3

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: NSC 177223
• 英文别名: 4-amino-5,8-tetrahydro-5-oxo-8-(β-D-ribofuranosyl)pyrido[2,3-d]pyrimidine-6-carboxamide；4-amino-5,8-dihydro-5-oxo-8-β-D-ribofuranosyl-pyrido[2,3-d]pyrimidine-6-carboxamide；NSC1777223；API-1；4-amino-5-oxo-8-β-D-ribofuranosyl-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid amide；4-amino-8-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide；4-Amino-5,6,7,8-tetrahydro-5-oxo-8-(beta-D-ribofuranosyl)pyrido[2,3-d]pyrimidine-6-carboxamide；4-amino-8-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide
• CAS: 36707-00-3
• 化学式: C₁₃H₁₅N₅O₆
• 分子量: 337.292
• InChiKey: SPBWHPXCWJLQRU-FITJORAGSA-N

物化性质

• 溶解度：
  DMF：微溶；二甲基亚砜：2mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  185
• 氢给体数：
  5
• 氢受体数：
  10

制备方法与用途

API-1是一种有效的Akt/PKB抑制剂，能够与PH结构域结合并抑制Akt向膜的转移。它能有效降低Akt的磷酸化水平，IC50约为0.8μM。API-1对PKB具有选择性，不会抑制PKC和PKA的激活。此外，API-1还能通过与TNF相关凋亡诱导配体（TRAIL）协同作用来诱导细胞凋亡。

反应信息

• 作为产物：
  描述：

  4-amino-2-methylsulfanyl-5-oxo-8-(tri-O-acetyl-β-D-ribofuranosyl)-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester 在 Raney Ni 氨 作用下， 以 乙醇 、 甲醇 为溶剂， 反应 16.0h， 以29%的产率得到NSC 177223
  参考文献：
  名称：

  [EN] COMPOUNDS USEFUL AS AKT/PKB MODULATORS AND USES THEREOF
  [FR] COMPOSÉS UTILES EN TANT QUE MODULATEURS AKT/PKB ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2012158197A3

文献信息

• Compositions to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
  申请人：Race Oncology Ltd.

  公开号：US10548876B2

  公开（公告）日：2020-02-04

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.

  本发明描述了通过提高单一疗法的疗效或减少副作用来改善以前因治疗效果不理想而受到限制的治疗剂的疗效的方法和组合物。这些方法和组合物尤其适用于双蒽或其衍生物、类似物或原药。
• Combinatorial methods to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
  申请人：Race Oncology Ltd.

  公开号：US11147800B2

  公开（公告）日：2021-10-19

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.

  本发明描述了通过提高单一疗法的疗效或减少副作用来改善以前因治疗效果不理想而受到限制的治疗剂的疗效的方法和组合物。这些方法和组合物尤其适用于双蒽或其衍生物、类似物或原药。
• Methods of detecting and treating a tumor expressing pT346 PDK1
  申请人：The Wistar Institute of Anatomy and Biology

  公开号：US11208478B2

  公开（公告）日：2021-12-28

  Therapeutic treatments of a tumor expressing pT346 PDK1, including glioma expressing pT346 PDK1, are disclosed.

  公开了表达 pT346 PDK1 的肿瘤（包括表达 pT346 PDK1 的胶质瘤）的治疗方法。
• Expansion and differentiation of inner ear supporting cells and methods of use thereof
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US11466252B2

  公开（公告）日：2022-10-11

  This disclosure relates to methods for expanding inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) and differentiating inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) to inner ear hair cells (e.g., atonal homolog 1 (Atoh1)+ inner ear hair cells) and the use of the inner hear supporting cells and hair cells, e.g., for identifying candidate therapeutic compounds for the treatment of hearing loss and balance loss. Additionally, the methods described herein can be used in the treatment of a subject having hearing loss and balance loss that would benefit from increased proliferation and differentiation of inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells).

  本公开涉及扩增内耳支持细胞（如Lgr5+内耳支持细胞）和将内耳支持细胞（如Lgr5+内耳支持细胞）分化为内耳毛细胞（如阿托纳同源物1（Atoh1）+内耳毛细胞）的方法，以及内耳支持细胞和毛细胞的用途，如用于鉴定治疗听力损失和平衡损失的候选治疗化合物。此外，本文所述的方法还可用于治疗听力损失和平衡失调患者，这些患者将受益于内耳支持细胞（如Lgr5+内耳支持细胞）的增殖和分化。
• EXPANSION AND DIFFERENTIATION OF INNER EAR SUPPORTING CELLS AND METHODS OF USE THEREOF
  申请人：Massachusetts Eye & Ear Infirmary

  公开号：EP3407901B1

  公开（公告）日：2021-07-21