N-acetyl-S-(((R)-6’-hydroxy-2’,4’,6’-trimethyl-7’-oxo-6’,7’-dihydrospiro[cyclopropane-1,5’-inden]-3’-yl)methyl)-L-cysteine | 238432-56-9

• 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
• 英文名称: N-acetyl-S-(((R)-6’-hydroxy-2’,4’,6’-trimethyl-7’-oxo-6’,7’-dihydrospiro[cyclopropane-1,5’-inden]-3’-yl)methyl)-L-cysteine
• 英文别名: N-acetyl-S-(((R)-6'-hydroxy-2',4',6'-trimethyl-7'-oxo-6',7'-dihydrospiro[cyclopropane-1,5'-inden]-3'-yl)methyl)-L-cysteine；(2R)-2-acetamido-3-[[(5'R)-5'-hydroxy-2',5',7'-trimethyl-4'-oxospiro[cyclopropane-1,6'-indene]-1'-yl]methylsulfanyl]propanoic acid
• CAS: 238432-56-9
• 化学式: C₂₀H₂₅NO₅S
• 分子量: 391.488
• InChiKey: WZCKDNYRVWLSIO-KXBFYZLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Fmoc-L-亮氨酸 、 N-acetyl-S-(((R)-6’-hydroxy-2’,4’,6’-trimethyl-7’-oxo-6’,7’-dihydrospiro[cyclopropane-1,5’-inden]-3’-yl)methyl)-L-cysteine 生成 (2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-[[(5'R)-5'-hydroxy-2',5',7'-trimethyl-4'-oxospiro[cyclopropane-1,6'-indene]-1'-yl]methylsulfanyl]propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoic acid
  参考文献：
  名称：

  Preparation and Biological Activity of Amino Acid and Peptide Conjugates of Antitumor Hydroxymethylacylfulvene

  摘要：

  The primary hydroxyl group in hydroxymethylacylfulvene, a potent antitumor drug, is readily replaced by thiols including cysteine, N-acetylcysteine, homocysteine, and glutathione. Best yields are obtained when reaction is carried out in the presence of dilute sulfuric acid. A variety of sulfur-containing analogues have been prepared, and their toxicity to tumor cells was examined.

  DOI：

  10.1021/jm0000315
• 作为产物：
  描述：

  N-乙酰-L-半胱氨酸 、 (-)-伊洛福芬 在 硫酸 作用下， 以 丙酮 为溶剂， 反应 22.0h， 以85%的产率得到N-acetyl-S-(((R)-6’-hydroxy-2’,4’,6’-trimethyl-7’-oxo-6’,7’-dihydrospiro[cyclopropane-1,5’-inden]-3’-yl)methyl)-L-cysteine
  参考文献：
  名称：

  Preparation and Biological Activity of Amino Acid and Peptide Conjugates of Antitumor Hydroxymethylacylfulvene

  摘要：

  The primary hydroxyl group in hydroxymethylacylfulvene, a potent antitumor drug, is readily replaced by thiols including cysteine, N-acetylcysteine, homocysteine, and glutathione. Best yields are obtained when reaction is carried out in the presence of dilute sulfuric acid. A variety of sulfur-containing analogues have been prepared, and their toxicity to tumor cells was examined.

  DOI：

  10.1021/jm0000315

文献信息

• AFFINITY ILLUDOFULVENE CONJUGATES
  申请人：AF Chemicals, LLC,

  公开号：US20210155583A1

  公开（公告）日：2021-05-27

  In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

  在该发明实施例中，用于治疗细胞群的组合物包括一种药物。该药物部分可以是伊卢多富烯类似物。在该发明实施例中，用于治疗细胞群的组合物包括亲和药物结合物（AMC）。亲和部分可以是抗体、抗体片段、受体蛋白、肽生长因子、抗血管生成蛋白、特异结合肽、蛋白酶可切割肽、糖肽、肽、肽毒素、蛋白毒素和寡核苷酸。亲和部分可以通过连接剂与药物共价结合。
• METHODS, COMPOSITIONS AND DEVICES FOR TREATING CANCER WITH ILLUDOFULVENES
  申请人：Kelner, Michael

  公开号：EP3667323A1

  公开（公告）日：2020-06-17

  The present invention relates to compositions, methods and devices for treating cancer with illudofulvenes including methods to detect the expression levels of genes encoding biomarkers in cancer patients and to predict the responsiveness of cancer patients to illudofulvenes.

  本发明涉及用紫杉醇治疗癌症的组合物、方法和装置，包括检测癌症患者体内编码生物标志物的基因表达水平和预测癌症患者对紫杉醇反应性的方法。
• Affinity medicant conjugate
  申请人：AF Chemicals, LLC

  公开号：US10285955B2

  公开（公告）日：2019-05-14

  In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.

  在本发明的一个实施方案中，一种用于治疗细胞群的组合物包含一种亲和药剂共轭物（AMC）。药剂分子可以是包括酰化芬在内的毒素或药物分子。亲和剂可以是抗体、结合蛋白、类固醇、脂质、生长因子、蛋白质、肽或非肽。亲和分子可以通过连接体与药物共价结合。新型连接体可根据溶液 pH 值定向连接半胱氨酸、精氨酸或赖氨酸残基，从而更灵活地保留和/或生成 AMC 中的特定表位。
• Affinity medicant conjugates
  申请人：AF Chemicals, LLC

  公开号：US11135182B2

  公开（公告）日：2021-10-05

  In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.

  在本发明的一个实施方案中，一种用于治疗细胞群的组合物包含一种亲和药剂共轭物（AMC）。药剂分子可以是包括酰化芬在内的毒素或药物分子。亲和剂可以是抗体、结合蛋白、类固醇、脂质、生长因子、蛋白质、肽或非肽。亲和分子可以通过连接体与药物共价结合。新型连接体可根据溶液 pH 值定向连接半胱氨酸、精氨酸或赖氨酸残基，从而更灵活地保留和/或生成 AMC 中的特定表位。
• Methods, compositions and devices for treating cancer with illudofulvenes
  申请人：AF Chemicals, LLC

  公开号：US11160807B1

  公开（公告）日：2021-11-02

  In an embodiment of the invention, a method of treating cancer includes screening to select a patient population that will respond to an Illudofulvene Analog composition based on the presence of one or more Transcription Coupled Repair (TCR) mutations, deletions or other events interfering with TCR biomarker expression in combination with upregulation of Myc and/or PTGR biomarker expression and treating the patient population with the Illudofulvene Analog composition.

  在本发明的一个实施方案中，治疗癌症的方法包括根据存在一种或多种转录偶联修复（TCR）突变、缺失或其他干扰TCR生物标志物表达的事件，结合Myc和/或PTGR生物标志物表达的上调，筛选出对Illudofulvene类似物组合物有反应的患者群体，并用Illudofulvene类似物组合物治疗该患者群体。