Dodecanoic acid,12-[[(2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-oxopentyl]amino]- | 391610-91-6

• 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: Dodecanoic acid,12-[[(2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-oxopentyl]amino]-
• 英文别名: 12-(N_α-tert-butoxycarbonyl-L-leucinoylamino)dodecanoic acid；Boc-Leu-12-aminododecanoic acid
• CAS: 391610-91-6
• 化学式: C₂₃H₄₄N₂O₅
• 分子量: 428.613
• InChiKey: SJNMQNICGJBGCB-IBGZPJMESA-N

物化性质

• 沸点：
  602.7±30.0 °C(Predicted)
• 密度：
  1.016±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  30.0
• 可旋转键数：
  16.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  104.73
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Dodecanoic acid,12-[[(2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-oxopentyl]amino]- 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.25h， 生成 8-O-(12-[L-leucinoylamino]dodecanoyl)-8-O-debutanoylthapsigargin
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Thapsigargin Analogues for Targeting Apoptosis to Prostatic Cancer Cells

  摘要：

  A series of thapsigargin (TG) analogues, containing an amino acid applicable for conjugation to a peptide specifically cleaved by prostate-specific antigen (PSA), has been prepared to develop the drug-moiety of prodrugs for treatment of prostatic cancer. The analogues were synthesized by converting TG into O-8-debutanoylthapsigargin (DBTG) and esterifying O-8 of DBTG with various amino acid linkers. The compounds were evaluated for their ability to elevate the cytosolic Ca2+ concentration ([Ca2+](i)) in TSU-Pr1 cells, their ability to inhibit the rabbit skeletal muscle SERCA pump, and their ability to induce apoptosis in TSU-Pr1 human prostatic cancer cells. The activity of analogues, in which DBTG were esterified with w-amino acids [HOOC-(CH2)(n),NH2, n = 5-7, 10, 11], increased with the linker length. Analogues with 3-[4-(L-leucinoylamino)phenyl]propanoyl, 6-(L-leucinoylamino)hexanoyl, and 12-(L-serinoylamino)dodecanoyl were considerably less active than TG, and analogues with 12-(L-alaninoylamino)dodecanoyl and 12-(L-phenylalaninoylamino)dodecanoyl were almost as active as TG. The 12-(L-leucinoylamino)dodecanoyl gave an analogue equipotent with TG, making this compound promising as the drug-moiety of a PSA sensitive prodrug of TG.

  DOI：

  10.1021/jm010985a
• 作为产物：
  描述：

  12-(Nα-tert-butoxycarbonyl-L-leucinoylamino)dodecanoic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以95%的产率得到Dodecanoic acid,12-[[(2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-oxopentyl]amino]-
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Thapsigargin Analogues for Targeting Apoptosis to Prostatic Cancer Cells

  摘要：

  A series of thapsigargin (TG) analogues, containing an amino acid applicable for conjugation to a peptide specifically cleaved by prostate-specific antigen (PSA), has been prepared to develop the drug-moiety of prodrugs for treatment of prostatic cancer. The analogues were synthesized by converting TG into O-8-debutanoylthapsigargin (DBTG) and esterifying O-8 of DBTG with various amino acid linkers. The compounds were evaluated for their ability to elevate the cytosolic Ca2+ concentration ([Ca2+](i)) in TSU-Pr1 cells, their ability to inhibit the rabbit skeletal muscle SERCA pump, and their ability to induce apoptosis in TSU-Pr1 human prostatic cancer cells. The activity of analogues, in which DBTG were esterified with w-amino acids [HOOC-(CH2)(n),NH2, n = 5-7, 10, 11], increased with the linker length. Analogues with 3-[4-(L-leucinoylamino)phenyl]propanoyl, 6-(L-leucinoylamino)hexanoyl, and 12-(L-serinoylamino)dodecanoyl were considerably less active than TG, and analogues with 12-(L-alaninoylamino)dodecanoyl and 12-(L-phenylalaninoylamino)dodecanoyl were almost as active as TG. The 12-(L-leucinoylamino)dodecanoyl gave an analogue equipotent with TG, making this compound promising as the drug-moiety of a PSA sensitive prodrug of TG.

  DOI：

  10.1021/jm010985a

文献信息

• Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics
  作者：Ilari Tarvainen、Tomáš Zimmermann、Pia Heinonen、Maria Helena Jäntti、Jari Yli-Kauhaluoma、Virpi Talman、Henrik Franzyk、Raimo K. Tuominen、Søren Brøgger Christensen

  DOI：10.1021/acsmedchemlett.9b00554

  日期：2020.5.14

  cytotoxic 4β-phorbol esters toward cancer tissue was attempted by conjugating a 4β-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors

  尝试通过将4β-pborbol衍生物与癌症组织中表达的蛋白酶前列腺特异性抗原（PSA）和前列腺特异性膜抗原（PSMA）的底物缀合来尝试将癌性4β-佛波醇酯靶向癌组织。假设亲水肽部分可防止前药渗透到细胞中并防止与PKC相互作用。设想在癌症肿瘤中切割该肽以释放亲脂性细胞毒素，其随后渗透到癌细胞中。4-7-佛波醇酯是从巴豆（Croton tiglium）种子中分离得到的4β-佛波醇制备的，而肽是通过固相合成法制备的。细胞测定显示前药可激活PKC，并能有效杀死肽酶阳性和肽酶阴性细胞。