| 1307864-98-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 1307864-98-7
• 化学式: C₂₄H₂₈N₄O₄
• 分子量: 436.511
• InChiKey: JFMQOGPJYHPFGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.58
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  76.38
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  在 哌啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Development of a Peptide–Drug Conjugate for Prostate Cancer Therapy

  摘要：

  TGX-221 is a highly potent phosphoinositide 3-kinase beta (PI3K beta) inhibitor that holds great promise as a novel chemotherapeutic agent to treat prostate cancer. However, poor solubility and lack of targetability limit its therapeutic applications. The objective of this present study is to develop a peptide-drug conjugate to specifically deliver TGX-221 to HER2 overexpressing prostate cancer cells. Four TGX-221 derivatives with added hydroxyl groups were synthesized for peptide conjugation. Among them, TGX-D1 exhibited a similar bioactivity to TGX-221, and it was selected for conjugation with a peptide promoiety containing a HER2-targeting ligand and a prostate specific antigen (PSA) substrate linkage. From this selection, the peptide-drug conjugate was proven to be gradually cleaved by PSA to release TGX-D1. Cellular uptake of the peptide-drug conjugate was significantly higher in prostate cancer cells compared to the parent drug. Moreover, both the peptide-drug conjugate and its cleaved products demonstrated comparable activities as the parent drug TGX-D1. Our results suggest that this peptide-drug conjugate may provide a promising chemotherapy for prostate cancer patients.

  DOI：

  10.1021/mp200007b
• 作为产物：
  描述：

  9-溴-2-羟基-7-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium tetrahydroborate 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 29.0h， 生成
  参考文献：
  名称：

  Development of a Peptide–Drug Conjugate for Prostate Cancer Therapy

  摘要：

  TGX-221 is a highly potent phosphoinositide 3-kinase beta (PI3K beta) inhibitor that holds great promise as a novel chemotherapeutic agent to treat prostate cancer. However, poor solubility and lack of targetability limit its therapeutic applications. The objective of this present study is to develop a peptide-drug conjugate to specifically deliver TGX-221 to HER2 overexpressing prostate cancer cells. Four TGX-221 derivatives with added hydroxyl groups were synthesized for peptide conjugation. Among them, TGX-D1 exhibited a similar bioactivity to TGX-221, and it was selected for conjugation with a peptide promoiety containing a HER2-targeting ligand and a prostate specific antigen (PSA) substrate linkage. From this selection, the peptide-drug conjugate was proven to be gradually cleaved by PSA to release TGX-D1. Cellular uptake of the peptide-drug conjugate was significantly higher in prostate cancer cells compared to the parent drug. Moreover, both the peptide-drug conjugate and its cleaved products demonstrated comparable activities as the parent drug TGX-D1. Our results suggest that this peptide-drug conjugate may provide a promising chemotherapy for prostate cancer patients.

  DOI：

  10.1021/mp200007b