1-isopropyl-1-[(4-chlorophenyl)sulfonyl]-3-n-propylurea

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-isopropyl-1-[(4-chlorophenyl)sulfonyl]-3-n-propylurea
• 英文别名: 1-(4-Chlorophenyl)sulfonyl-1-isopropyl-3-propyl-urea；1-(4-chlorophenyl)sulfonyl-1-propan-2-yl-3-propylurea
• 化学式: C₁₃H₁₉ClN₂O₃S
• 分子量: 318.824
• InChiKey: LIOSYTULIKGGRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-isopropyl-1-[(4-chlorophenyl)sulfonyl]-3-n-propylurea 在 sodium hydroxide 作用下， 生成 正丙胺 、 4-氯-N-异丙基苯磺酰胺
  参考文献：
  名称：

  Evidence for an isocyanate formation in the alkaline hydrolysis of N¹-alkyl derivatives of chlorpropamide, inhibitors of aldehyde dehydrogenase

  摘要：

  异氰酸丙酯中间体的捕获和活化熵数据与醛脱氢酶抑制剂 1-烷基-1-[(4-氯苯基)磺酰基]-3-正丙基脲（氯丙酰胺的 N1-烷基衍生物）水解的消除-加成机制 AxhDH+ DN(E1cB) 相一致。

  DOI：

  10.1039/c39930000946
• 作为产物：
  描述：

  异氰酸丙酯 、 4-氯-N-异丙基苯磺酰胺 在 三乙胺 作用下， 以64%的产率得到1-isopropyl-1-[(4-chlorophenyl)sulfonyl]-3-n-propylurea
  参考文献：
  名称：

  N1-alkyl-substituted derivatives of chlorpropamide as inhibitors of aldehyde dehydrogenase

  摘要：

  On the basis of an earlier observation that the N1-ethyl derivative of the hypoglycemic agent chlorpropamide (CP) inhibited aldehyde dehydrogenase (AlDH) in rats without producing hypoglycemia, we undertook a structure-activity study to assess the effect of altering the alkyl substituents at N1 and N3, as well as substituting O for N at the latter position, and evaluated these analogues for their effect on AlDH in vivo and in vitro. Our results suggest that only those CP analogues that can release alkyl isocyanates nonenzymatically inhibited AlDH. Increasing the steric bulk of the N1-alkyl substituent enhanced isocyanate formation and AlDH inhibition. CP analogues that lacked the NH group at N3 or were otherwise incapable of alkyl isocyanate release were inactive.

  DOI：

  10.1021/jm00126a032

文献信息

• [EN] MULTI- API LOADING PRODRUGS<br/>[FR] PROMÉDICAMENTS CHARGÉS DE MULTIPLES PRINCIPES ACTIFS
  申请人：ALKERMES INC

  公开号：WO2012088441A1

  公开（公告）日：2012-06-28

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam- amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.

  本发明通过将多个母药分子附着在载体基团上，并延长母药在患者服用后释放和吸收的时间，从而实现此目的，并提供每剂次比母药本身更长的作用时间。前药偶联物适用于异杂环、内酰胺、酰胺、磺酰胺、氨基甲酸酯、脲、苯甲酰胺、酰基苯胺、环状酰胺和三级胺含有母药，该母药在酰胺氮或氧原子处以不稳定的醛类前药基团取代。前药的载体基团可以是疏水性的，在生理条件下降低母药的极性和溶解度。
• Multi-API Loading Prodrugs
  申请人：Zeidan Tarek A.

  公开号：US20120202823A1

  公开（公告）日：2012-08-09

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam- amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.
• MULTI-API LOADING PRODRUGS
  申请人：Alkermes Pharma Ireland Limited

  公开号：US20180194732A1

  公开（公告）日：2018-07-12

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam- amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.
• N1-alkyl-substituted derivatives of chlorpropamide as inhibitors of aldehyde dehydrogenase
  作者：Herbert T. Nagasawa、James A. Elberling、Eugene G. DeMaster、Frances N. Shirota

  DOI：10.1021/jm00126a032

  日期：1989.6

  On the basis of an earlier observation that the N1-ethyl derivative of the hypoglycemic agent chlorpropamide (CP) inhibited aldehyde dehydrogenase (AlDH) in rats without producing hypoglycemia, we undertook a structure-activity study to assess the effect of altering the alkyl substituents at N1 and N3, as well as substituting O for N at the latter position, and evaluated these analogues for their effect on AlDH in vivo and in vitro. Our results suggest that only those CP analogues that can release alkyl isocyanates nonenzymatically inhibited AlDH. Increasing the steric bulk of the N1-alkyl substituent enhanced isocyanate formation and AlDH inhibition. CP analogues that lacked the NH group at N3 or were otherwise incapable of alkyl isocyanate release were inactive.
• Evidence for an isocyanate formation in the alkaline hydrolysis of N¹-alkyl derivatives of chlorpropamide, inhibitors of aldehyde dehydrogenase
  作者：M. Bergon、A. Vigroux、P. Tisnès

  DOI：10.1039/c39930000946

  日期：——

  Trapping of a propyl isocyanate intermediate and entropies of activation data are consistent with an elimination–addition mechanism AxhDH+ DN(E1cB) for the hydrolysis of 1-alkyl-1-[(4-chlorophenyl)sulfonyl]-3-n-propylurea, the N1-alkyl derivatives of chlorpropamide, inhibitors of aldehyde dehydrogenase.

  异氰酸丙酯中间体的捕获和活化熵数据与醛脱氢酶抑制剂 1-烷基-1-[(4-氯苯基)磺酰基]-3-正丙基脲（氯丙酰胺的 N1-烷基衍生物）水解的消除-加成机制 AxhDH+ DN(E1cB) 相一致。