N-t-butyloxycarbonyl-N-methylglycine anhydride | 70533-97-0

• 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-t-butyloxycarbonyl-N-methylglycine anhydride
• 英文别名: N-t-butoxycarbonyl-N-methylglycine anhydride；N-t-Butyloxycarbonyl-N-methylglycine anhydride；[2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetyl] 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetate
• CAS: 70533-97-0
• 化学式: C₁₆H₂₈N₂O₇
• 分子量: 360.408
• InChiKey: NUZYIMPZYULINV-UHFFFAOYSA-N

物化性质

• 沸点：
  418.8±34.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-t-butyloxycarbonyl-N-methylglycine anhydride 、 羟丙基甲基纤维素邻苯二甲酸酯 在 三乙胺 作用下， 反应 8.0h， 以87.5%的产率得到tert-butoxycarbonyl-1-isobutyl-1H-imidazo[4,5-c]quinolin-4-sarcosine
  参考文献：
  名称：

  High penetration prodrug compositions of 1H-imidazo[4,5-c]quinolin-4-amines and 1H-imidazo[4,5-c]quinolin-4-amine-related compounds and uses thereof

  摘要：

  本发明提供了1H-咪唑[4,5-c]喹啉-4-胺及其相关化合物的新型高渗透性组合物（HPC）或高渗透性前药（HPP），能够高效穿越生物屏障。HPP能够在穿越生物屏障后转化为母药或药物代谢物，从而可以治疗母药或代谢物能够治疗的疾病。此外，HPP能够到达母药无法访问或无法在目标区域产生足够浓度的区域，因此提供了新颖的治疗方式。HPP可以通过各种给药途径给予受试者，例如局部给药到病变部位以获得高浓度，或系统性给药到生物体内并以更快的速度进入循环系统。

  公开号：

  US09567329B2
• 作为产物：
  描述：

  叔丁氧羰酰基肌氨酸 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-t-butyloxycarbonyl-N-methylglycine anhydride
  参考文献：
  名称：

  万古霉素在水溶液中结合细菌细胞壁类似物时，非极性和离子力之间的协同作用。

  摘要：

  临床上重要的糖肽抗生素万古霉素与革兰氏阳性细菌的细菌细胞壁肽结合，后者终止于-Lys-D-Ala-D-Ala，从而抑制细胞壁合成，导致细胞死亡。我们已经通过埃德曼降解去除了万古霉素的N末端亮氨酸残基，并用N-Me-Gly，N-Me-D-Ala，乙酰基，丁基和异己基酰化了残基2暴露的氨基，从而生成了新的万古霉素类似物。通过NMR技术和UV光谱法研究了万古霉素和这些万古霉素类似物与细菌细胞壁类似物di-N-Ac-L-Lys-D-Ala-D-Ala（DALAA）的结合。

  DOI：

  10.7164/antibiotics.48.805

文献信息

• 1H-咪唑并[4,5-c]喹啉-4-胺类及其相关化合 物的前药
  申请人：于崇曦

  公开号：CN106432226B

  公开（公告）日：2019-08-30

  本发明涉及具有通式1“结构式1”或通式2“结构式2”的1H‑咪唑并[4,5‑c]喹啉‑4‑胺类及其相关化合物的前药的设计与合成，其可由1H‑咪唑并[4,5‑c]喹啉‑4‑胺类及其相关化合物与适当的乙酸酐或乙酰氯反应制得。实验结果表明超过90％的前药能在几分钟内回到母药结构，可用于治疗人或动物的任何1H‑咪唑并[4,5‑c]喹啉‑4‑胺类及其相关化合物可治疗的状态，避免1H‑咪唑并[4,5‑c]喹啉‑4‑胺类及其相关化合物所产生的大多数副作用。通过前药的控释透皮给药系统可使血液中1H‑咪唑并[4,5‑c]喹啉‑4‑胺类及其相关化合物的浓度稳定在最佳的治疗浓度，提升疗效并减少副作用。
• HIGH PENETRATION PRODRUG COMPOSITIONS OF 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINES AND 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINE-RELATED COMPOUNDS
  申请人：YU Chongxi

  公开号：US20100021394A1

  公开（公告）日：2010-01-28

  The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of 1H-imidazo[4,5-c]quinolin-4-amines and 1H-imidazo[4,5-c]quinolin-4-amine-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

  本发明提供了一种新型高穿透力化合物（HPC）或高穿透力前药（HPP）的组合物，其中包括1H-咪唑[4,5-c]喹啉-4-胺和1H-咪唑[4,5-c]喹啉-4-胺相关化合物。这些化合物能够高效地穿过生物屏障。HPP可以在穿过生物屏障后被转化为原始活性药物或药物代谢物，从而可以治疗与原始药物或代谢物相关的疾病。此外，HPP能够到达原始药物无法接触到或无法在目标区域产生足够浓度的区域，从而提供新型治疗方法。HPP可以通过各种给药途径给予受试者，例如在治疗区域局部给药以高浓度作用或系统性给药给生物受试者，并以更快的速度进入全身循环。
• HIGH PENETRATION PRODRUG COMPOSITIONS OF 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINES AND 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINE-RELATED COMPOUNDS AND USES THEREOF
  申请人：YU Chongxi

  公开号：US20130131100A1

  公开（公告）日：2013-05-23

  The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of 1H-imidazo[4,5-c]quinolin-4-amines and 1H-imidazo[4,5-c]quinolin-4-amine-related compounds, which are capable of crossing biological barriers with high penetration efficiency. The HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

  本发明提供了1H-咪唑[4,5-c]喹啉-4-胺和1H-咪唑[4,5-c]喹啉-4-胺相关化合物的新型高渗透性组合物（HPC）或高渗透性前药（HPP），能够以高渗透效率穿过生物屏障。HPP能够在穿过生物屏障后转化为母药或药物代谢物，从而可以治疗母药或代谢物所能治疗的病症。此外，HPP能够到达母药可能无法进入或在目标区域提供足够浓度的区域，从而提供新型治疗方法。HPP可以通过各种给药途径给予受试者，例如，局部给药于具有高浓度的病症作用部位或系统性给药于生物体中并以更快的速率进入全身循环。
• POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINES AND RELATED COMPOUNDS WITH VERY HIGH SKIN PENETRATION RATES
  申请人：Yu, Chongxi

  公开号：EP3176169A1

  公开（公告）日：2017-06-07

  The novel positively charged pro-drugs of 1H-imidazo[4, 5-c]quinolin-4-amines and related compounds in the general formula (1) 'Structure 1' or formula (2) 'Structure 2' were designed and synthesized. The compounds of the general formula (1) 'Structure 1' or formula (2) 'Structure 2' indicated above can be prepared from 1H-imidazo[4, 5-c]quinolin-4-amines and related compounds, by reaction with suitable acetic anhydride or acetic chloride. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the prodrug. When the molecules of membrane move, the membrane may 'crack' a little bit due to the bonding of the prodrug. This will let the prodrug insert into the membrane. At pH 7.4, only about 99% of the amino group is protonated. When the amino group is not protonated, the bonding between the amino group of the prodrug and the phosphate head group of the membrane will disassociate, and the prodrug will enter the membrane completely. When the amino group of the prodrug flips to the other side of the membrane and thus becomes protonated, then the prodrug is pulled into the cytosol, a semi-liquid concentrated aqueous solution or suspension. The results suggest that the pro-drugs diffuse through human skin -25 times faster than do 1H-imidazo[4, 5-c]quinolin-4-amines and related compounds. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any 1H-imidazo[4,5-c]quinolin-4-amines and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of 1H-imidazo[4,5-c] quinolin-4-amines and related compounds. Controlled transdermal administration systems of the prodrug enables 1H-imidazo[4, 5-c]quinolin-4-amines and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of 1H-imidazo[4, 5-c]quinolin-4-amines and related compounds.

  设计并合成了通式（1）"结构 1 "或式（2）"结构 2 "的 1H-咪唑并[4，5-c]喹啉-4-胺及相关化合物的新型带正电的原药。上述通式（1）"结构 1 "或式（2）"结构 2 "的化合物可由 1H-咪唑并[4，5-c]喹啉-4-胺和相关化合物通过与合适的醋酸酐或醋酰氯反应制备而成。这些原药带正电荷的氨基不仅在很大程度上增加了药物在水中的溶解度，而且还与膜的磷酸头基上的负电荷结合。这种结合会对膜产生一些干扰，可能会为原药的亲脂部分腾出一些空间。当膜分子移动时，由于原药的键合作用，膜可能会 "裂开 "一点。这将使原药插入膜中。在 pH 值为 7.4 时，只有约 99% 的氨基被质子化。当氨基没有被质子化时，原药的氨基与膜的磷酸头基之间的键就会脱离，原药就会完全进入膜中。当原形药的氨基翻转到膜的另一侧从而质子化时，原形药就会被拉入半流体浓缩水溶液或悬浮液的细胞质中。结果表明，原药在人体皮肤中的扩散速度是 1H-咪唑并[4, 5-c]喹啉-4-胺和相关化合物的 25 倍。在血浆中，90% 以上的原药可在几分钟内变回母药。这些原药可用于治疗人类或动物体内任何可治疗的 1H-咪唑并[4,5-c]喹啉-4-胺及相关化合物疾病。原药可以透皮给药，用于任何类型的医疗，并避免 1H-咪唑并[4,5-c]喹啉-4-胺和相关化合物的大部分副作用。原药的可控透皮给药系统可使 1H-咪唑并[4,5-c]喹啉-4-胺和相关化合物不断达到最佳治疗血药浓度，从而提高疗效并减少 1H-咪唑并[4,5-c]喹啉-4-胺和相关化合物的副作用。
• "Glycylcyclines". 3. 9-Aminodoxycyclinecarboxamides
  作者：Timothy C. Barden、Brian L. Buckwalter、Raymond T. Testa、Peter J. Petersen、Ving J. Lee

  DOI：10.1021/jm00046a003

  日期：1994.9

  A series of 9-(acylamino)doxycycline derivatives has been prepared. These analogs exhibit good activity against both tetracycline sensitive and tetracycline resistant Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria that are encoded with the efflux and ribosomal resistance gene factors. N,N-Dialkylglycylamido derivatives possessed the highest activity. Replacement of glycine moiety with other amino acids did not further enhance the activity.