tert-butyl N-[(2S)-1-[(2S)-2-[[4-[[(2R,3S)-3-[[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl]oxycarbonylamino]-2-hydroxy-4-phenylbutyl]-(2-methylpropyl)sulfamoyl]phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate | 791071-77-7

• 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: tert-butyl N-[(2S)-1-[(2S)-2-[[4-[[(2R,3S)-3-[[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl]oxycarbonylamino]-2-hydroxy-4-phenylbutyl]-(2-methylpropyl)sulfamoyl]phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 791071-77-7
• 化学式: C₄₃H₆₃N₅O₁₁S
• 分子量: 858.066
• InChiKey: ZEIHCUXBFGMDMN-NTLBRCOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  60
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  211
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-1-[(2S)-2-[[4-[[(2R,3S)-3-[[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl]oxycarbonylamino]-2-hydroxy-4-phenylbutyl]-(2-methylpropyl)sulfamoyl]phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以61%的产率得到[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] N-[(2S,3R)-4-[[4-[[[(2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]methyl]phenyl]sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
  参考文献：
  名称：

  [EN] PRODRUGS CLEAVABLE BY CD26
  [FR] PROMEDICAMENTS POUVANT ETRE CLIVES A MOYEN DE CD26

  摘要：

  本发明提供了一种新的前药技术和新的前药，以增加药物的溶解度，调节血浆蛋白结合或增强药物的生物利用度。在本发明中，前药是治疗化合物和肽（例如四肽或六肽）的结合物，其中结合物可被二肽肽酶（更优选为CD26，也称为DPPIV，即二肽氨二肽酶IV）水解。本发明还提供了一种生产所述前药的方法，以增强药物在大脑和淋巴系统中的传递，并/或延长药物在血浆中的半衰期。

  公开号：

  WO2004098644A1
• 作为产物：
  描述：

  {(1S,2R)-3-[(4-Aminomethyl-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester 、 N-[(1,1-二甲基乙氧基)羰基]-L-缬氨酰-L-脯氨酸 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 20.0h， 以55%的产率得到tert-butyl N-[(2S)-1-[(2S)-2-[[4-[[(2R,3S)-3-[[(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl]oxycarbonylamino]-2-hydroxy-4-phenylbutyl]-(2-methylpropyl)sulfamoyl]phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  [EN] PRODRUGS CLEAVABLE BY CD26
  [FR] PROMEDICAMENTS POUVANT ETRE CLIVES A MOYEN DE CD26

  摘要：

  本发明提供了一种新的前药技术和新的前药，以增加药物的溶解度，调节血浆蛋白结合或增强药物的生物利用度。在本发明中，前药是治疗化合物和肽（例如四肽或六肽）的结合物，其中结合物可被二肽肽酶（更优选为CD26，也称为DPPIV，即二肽氨二肽酶IV）水解。本发明还提供了一种生产所述前药的方法，以增强药物在大脑和淋巴系统中的传递，并/或延长药物在血浆中的半衰期。

  公开号：

  WO2004098644A1

文献信息

• Prodrugs Cleavable by Cd26
  申请人：Balzarini Jan

  公开号：US20070275900A1

  公开（公告）日：2007-11-29

  The present invention provides a new prodrug technology and new prodrugs in order to increase the solubility, to modulate plasma protein binding or to enhance the biovailability of a drug. In the present invention the prodrugs are conjugates of a therapeutic compound and a peptide (eg tetrapeptide or hexapeptide) wherein the conjugate is cleavable by dipeptidyl-peptidases, more preferably by CD26, also known as DPPIV (dipeptidyl aminodipeptidase IV). The present invention furthermore provides a method of producing said prodrugs, to enhance brain and lymphatic delivery of drugs and/or to extend drug half-lives in plasma.

  本发明提供了一种新的前药技术和新的前药，以增加药物的溶解度，调节血浆蛋白结合或增强药物的生物利用度。在本发明中，前药是治疗化合物和肽（例如四肽或六肽）的结合物，其中结合物可被二肽基-肽酶（更好地是CD26，也称为DPPIV（二肽基氨肽酰二肽酶IV））水解。本发明还提供了一种生产所述前药的方法，以增强药物在脑和淋巴中的递送和/或延长药物在血浆中的半衰期。
• Hiv Prodrugs Cleavable by Cd26
  申请人：De Kock Herman Augustinus

  公开号：US20080214648A1

  公开（公告）日：2008-09-04

  The present invention provides new prodrugs which are conjugates of a therapeutic compound and a peptide wherein the conjugate is cleavable by dipeptidyl-peptidases, more preferably by CD26, also known as DPPIV (dipeptidyl aminodipeptidase IV). The present prodrugs have the formula the stereoisomeric forms and salts thereof, wherein n is 1 to 5; Y is proline, alanine, hydroxyproline, dihydroxyproline, thiazolidinecarboxylic acid (thioproline), dehydroproline, pipecolic acid (L-homoproline), azetidinecarboxylic acid, aziridinecarboxylic acid, glycine, serine, valine, leucine, isoleucine and threonine; X is selected from any amino acid in the D- or L-configuration; X and Y in each repeat of [Y-X] are chosen independently from one another and independently from other repeats; Z is a direct bond or a bivalent straight or branched saturated hydrocarbon group having from 1 to 4 carbon atoms; R 1 is an aryl, heteroaryl, aryloxy, heteroaryloxy, aryloxyC 1-4 alkyl, heterocycloalkyloxy, heterocycloalkylC 1-4 alkyloxy, heteroaryloxyC 1-4 alkyl, heteroarylC 1-4 alkyloxy; R 2 is arylC 1-4 alkyl; R 3 is C 1-10 alkyl, C 2-6 alkenyl or C 3-7 cycloalkylC 1-4 alkyl; R 4 is hydrogen or C 1-4 alkyl. The present invention furthermore provides the use of said prodrugs as medicines as well as a method of producing said prodrugs.
• US8236756B2
  申请人：——

  公开号：US8236756B2

  公开（公告）日：2012-08-07
• [EN] PRODRUGS CLEAVABLE BY CD26<br/>[FR] PROMEDICAMENTS POUVANT ETRE CLIVES A MOYEN DE CD26
  申请人：LEUVEN K U RES & DEV

  公开号：WO2004098644A1

  公开（公告）日：2004-11-18

  The present invention provides a new prodrug technology and new prodrugs in order to increase the solubility, to modulate plasma protein binding or to enhance the biovailability of a drug. In the present invention the prodrugs are conjugates of a therapeutic compound and a peptide (eg tetrapeptide or hexapeptide) wherein the conjugate is cleavable by dipeptidyl-peptidases, more preferably by CD26, also known as DPPIV (dipeptidyl aminodipeptidase IV). The present invention furthermore provides a method of producing said prodrugs, to enhance brain and lymphatic delivery of drugs and/or to extend drug half-lives in plasma.

  本发明提供了一种新的前药技术和新的前药，以增加药物的溶解度，调节血浆蛋白结合或增强药物的生物利用度。在本发明中，前药是治疗化合物和肽（例如四肽或六肽）的结合物，其中结合物可被二肽肽酶（更优选为CD26，也称为DPPIV，即二肽氨二肽酶IV）水解。本发明还提供了一种生产所述前药的方法，以增强药物在大脑和淋巴系统中的传递，并/或延长药物在血浆中的半衰期。