1-(3-chloropropyl)-N-acetylcytosine | 1178551-04-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(3-chloropropyl)-N-acetylcytosine
• 英文别名: 1-(3-chloropropyl)-N4-acetylcytosine；N-[1-(3-chloropropyl)-2-oxopyrimidin-4-yl]acetamide
• CAS: 1178551-04-6
• 化学式: C₉H₁₂ClN₃O₂
• 分子量: 229.666
• InChiKey: SANIMCUBDSVBCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3-chloropropyl)-N-acetylcytosine 在 sodium azide 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以64%的产率得到N⁴-Acetyl-1-(3-azido-propyl)-cytosin
  参考文献：
  名称：

  Peptidyl α-Ketoamides with Nucleobases, Methylpiperazine, and Dimethylaminoalkyl Substituents as Calpain Inhibitors

  摘要：

  A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA-CONH-R were synthesized and evaluated as inhibitors for the cystcine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood-brain barrier. Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-adenin-9-yl and Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-(4-methylpiperazin- l -yl) have been shown to have useful concentrations in the brain in animals. The best inhibitor for calpain I was Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-2-methoxyadenin-9-yl (K-i = 23 nM), and the best inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH2)(3)-adenin-9-yl (K-i = 68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl alpha-ketoamides, we have improved inhibitor potency by introducing a small hydrophobic group on the adenine ring. These inhibitors have good potential to be used in the treatment of neurodegenerative diseases.

  DOI：

  10.1021/jm901221v
• 作为产物：
  描述：

  N4-乙酰胞嘧啶 、 1-溴-3-氯丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以69%的产率得到1-(3-chloropropyl)-N-acetylcytosine
  参考文献：
  名称：

  Peptidyl α-Ketoamides with Nucleobases, Methylpiperazine, and Dimethylaminoalkyl Substituents as Calpain Inhibitors

  摘要：

  A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA-CONH-R were synthesized and evaluated as inhibitors for the cystcine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood-brain barrier. Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-adenin-9-yl and Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-(4-methylpiperazin- l -yl) have been shown to have useful concentrations in the brain in animals. The best inhibitor for calpain I was Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-2-methoxyadenin-9-yl (K-i = 23 nM), and the best inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH2)(3)-adenin-9-yl (K-i = 68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl alpha-ketoamides, we have improved inhibitor potency by introducing a small hydrophobic group on the adenine ring. These inhibitors have good potential to be used in the treatment of neurodegenerative diseases.

  DOI：

  10.1021/jm901221v

文献信息

• HETEROCYCLIC PEPTIDE KETOAMIDES
  申请人：Powers James C.

  公开号：US20110053858A1

  公开（公告）日：2011-03-03

  A novel class of peptide α-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA 2 -AA 1 -CO—NH—(CH 2 ) n —R 3 . Processes for the synthesis of peptidyl α-ketoamide derivatives. Compositions and methods for inhibiting cysteine proteases, inhibiting calpains, and treating disease caused by cysteine proteases and calpains are provided

  一种新型的肽α-酮酰胺类化合物，可用于选择性抑制卡尔帕因酶、选择性抑制半胱氨酸蛋白酶和一般抑制所有半胱氨酸蛋白酶，其化学式为M-AA2-AA1-CO—NH—(CH2)n—R3。还提供了合成肽基α-酮酰胺衍生物的方法、抑制半胱氨酸蛋白酶、抑制卡尔帕因酶、治疗由半胱氨酸蛋白酶和卡尔帕因酶引起的疾病的组合物和方法。
• Heterocyclic peptide ketoamides
  申请人：Powers James C.

  公开号：US08518885B2

  公开（公告）日：2013-08-27

  A novel class of peptide α-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA2-AA1-CO—NH—(CH2)n—R3. Processes for the synthesis of peptidyl α-ketoamide derivatives. Compositions and methods for inhibiting cysteine proteases, inhibiting calpains, and treating disease caused by cysteine proteases and calpains are provided.

  一种新型的肽α-酮酰胺类化合物，适用于选择性抑制卡尔帕因酶、选择性抑制半胱氨酸蛋白酶和一般抑制所有半胱氨酸蛋白酶，其化学式为M-AA2-AA1-CO—NH—(CH2)n—R3。提供了合成肽α-酮酰胺衍生物的方法。还提供了抑制半胱氨酸蛋白酶、抑制卡尔帕因酶和治疗由半胱氨酸蛋白酶和卡尔帕因酶引起的疾病的组合物和方法。
• US8518885B2
  申请人：——

  公开号：US8518885B2

  公开（公告）日：2013-08-27
• [EN] HETEROCYCLIC PEPTIDE KETOAMIDES<br/>[FR] CÉTOAMIDES PEPTIDIQUES HÉTÉROCYCLIQUES
  申请人：GEORGIA TECH RES INST

  公开号：WO2009099416A1

  公开（公告）日：2009-08-13

  A novel class of peptide α-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA2-AA1-CO-NH-(CH2)n-R3. Processes for the synthesis of peptidyl α-ketoamide derivatives. Compositions and methods for inhibiting cysteine proteases, inhibiting calpains, and treating disease caused by cysteine proteases and calpains are provided.
• Peptidyl α-Ketoamides with Nucleobases, Methylpiperazine, and Dimethylaminoalkyl Substituents as Calpain Inhibitors
  作者：Asli Ovat、Zhao Zhao Li、Christina Y. Hampton、Seneshaw A. Asress、Facundo M. Fernández、Jonathan D. Glass、James C. Powers

  DOI：10.1021/jm901221v

  日期：2010.9.9

  A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA-CONH-R were synthesized and evaluated as inhibitors for the cystcine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood-brain barrier. Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-adenin-9-yl and Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-(4-methylpiperazin- l -yl) have been shown to have useful concentrations in the brain in animals. The best inhibitor for calpain I was Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-2-methoxyadenin-9-yl (K-i = 23 nM), and the best inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH2)(3)-adenin-9-yl (K-i = 68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl alpha-ketoamides, we have improved inhibitor potency by introducing a small hydrophobic group on the adenine ring. These inhibitors have good potential to be used in the treatment of neurodegenerative diseases.