4(S)-t-butoxycarbonylamino-N-butyl-3(S)-hydroxy-6-methylheptanamide | 100002-49-1

• 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: 4(S)-t-butoxycarbonylamino-N-butyl-3(S)-hydroxy-6-methylheptanamide
• 英文别名: tert-butyl N-[(3S,4S)-1-(butylamino)-3-hydroxy-6-methyl-1-oxoheptan-4-yl]carbamate
• CAS: 100002-49-1
• 化学式: C₁₇H₃₄N₂O₄
• 分子量: 330.468
• InChiKey: HDUJISVMBRBONX-KBPBESRZSA-N

物化性质

• 沸点：
  511.2±45.0 °C(Predicted)
• 密度：
  1.013±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4(S)-t-butoxycarbonylamino-N-butyl-3(S)-hydroxy-6-methylheptanamide 在 盐酸 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-(4-(((2S,3S)-1-((3S,4S)-1-(butylamino)-3-hydroxy-6-methyl-1-oxoheptan-4-ylamino)-3-methyl-1-oxopentan-2-yl)carbamoyl)phenoxy)benzoic acid benzyl ester
  参考文献：
  名称：

  Plasmepsin II inhibition and antiplasmodial activity of Primaquine–Statine `double-drugs'

  摘要：

  Statine-based inhibitors of Plasmepsin II (PLMII) coupled with Primaquine have been designed using the 'double-drug' approach. The IC50 values for PLMII inhibition ranged from 0.59 to 400 nM and the best IC50 value for inhibition of Plasmodium falciparum growth in vitro was 0.4 muM, which represent a remarkable improvement compared to other statine-based PLMII inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.030
• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-4-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 N-甲基吗啉 、 sodium hydroxide 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 zinc dibromide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 4(S)-t-butoxycarbonylamino-N-butyl-3(S)-hydroxy-6-methylheptanamide
  参考文献：
  名称：

  High Antiplasmodial Activity of Novel Plasmepsins I and II Inhibitors

  摘要：

  The aim of this study was to develop new antiplasmodial compounds acting through distinct mechanisms during both the liver and the blood stages of the parasite life cycle. Compounds were designed on the basis of the "double-drug" approach: primaquine, which has been linked to statine-based inhibitors of plasmepsins (PLMs), the plasmodial aspartic proteases involved in degradation of hemeoglobin. The compounds were tested in vitro for anti-PLM I/PLM II activities and against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of P. falciparum. An antiplasmodial activity (IC50) as low as 0.1 mu M was obtained, an excellent improvement in comparison with inhibitors previously reported (IC50 = 2 - 20 mu M). The killing activity was equally directed against both P. falciparum strains and was correlated to lipophilicity (calculated as ALogP), for all compounds but one (9). All compounds inhibited PLM I and PLM II in the nanomolar range (K-i = 1 - 700 nM). The most promising compounds (2, 6, 10) were not cytotoxic against human fibroblasts at 100 mu M and were highly selective for PLMs vs human cathepsin D.

  DOI：

  10.1021/jm061033d

文献信息

• New renin-inhibitory peptides and their use
  申请人：SANKYO COMPANY LIMITED

  公开号：EP0152255A2

  公开（公告）日：1985-08-21

  Compounds of formula wherein R' represents alkyl having an α-amino or protected α-amino substituent and an aryl, heterocyclic or heterocyclic- dithio substituent; R2 represents a variety of aliphatic and cycloaliphatic hydrocarbon groups, which may be substituted; R3 represents isobutyl, sec-butyl, benzyl or (C3-CS cyclo- elkyl)methyl; and X represents a group of formula -CH(-A-R")-Y) (in which: A represents a single bond or an alkylene group: R4 represents an optionally protected carboxy group, an optionally N-substituted carbamoyl group, an optionally N-substituted carbazoyl group or an acyl group; and Y represents a hydroxy group, a mercapto group or a formyl group), or a group of formula -P(O)(R5)-OH (in which R5 represents an alkyl group having at least one optionally protected carboxy, N-substituted carbamoyl, optionally N-substituted carbazoyl, C2-C7 aliphatic carboxylic acyl or aromatic carboxylic acyl substituent)]; and their salts are renin inhibitors, which may be used in the treatment of angiotensin-induced hypertension.

  式中的化合物 式中 R'代表具有α-氨基或受保护α-氨基取代基的烷基，以及芳基、杂环或杂环-二硫代基； R2 代表各种可被取代的脂肪族和环脂族烃基； R3 代表异丁基、仲丁基、苄基或（C3-CS 环烷基）甲基；以及 X 代表式 -CH(-A-R")-Y)的基团 其中A 代表单键或亚烷基：R4 代表任选受保护的羧基、任选 N-取代的氨基甲酰基、任选 N-取代的咔唑酰基或酰基；Y 代表羟基、巯基或甲酰基），或 式中-P(O)(R5)-OH 的基团 (其中 R5 代表具有至少一个任选保护的羧基、N-取代的氨基甲酰基、任选 N-取代的咔唑酰基、C2-C7 脂肪族羧酰基或芳香族羧酰基取代基的烷基）]；它们的盐类是肾素抑制剂，可用于治疗血管紧张素诱导的高血压。
• Plasmepsin II inhibition and antiplasmodial activity of Primaquine–Statine `double-drugs'
  作者：Sergio Romeo、Mario Dell'Agli、Silvia Parapini、Luca Rizzi、Germana Galli、Monica Mondani、Anna Sparatore、Donatella Taramelli、Enrica Bosisio

  DOI：10.1016/j.bmcl.2004.03.030

  日期：2004.6

  Statine-based inhibitors of Plasmepsin II (PLMII) coupled with Primaquine have been designed using the 'double-drug' approach. The IC50 values for PLMII inhibition ranged from 0.59 to 400 nM and the best IC50 value for inhibition of Plasmodium falciparum growth in vitro was 0.4 muM, which represent a remarkable improvement compared to other statine-based PLMII inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.
• US4698329A
  申请人：——

  公开号：US4698329A

  公开（公告）日：1987-10-06
• High Antiplasmodial Activity of Novel Plasmepsins I and II Inhibitors
  作者：Mario Dell'Agli、Silvia Parapini、Germana Galli、Nadia Vaiana、Donatella Taramelli、Anna Sparatore、Peng Liu、Ben M. Dunn、Enrica Bosisio、Sergio Romeo

  DOI：10.1021/jm061033d

  日期：2006.12.1

  The aim of this study was to develop new antiplasmodial compounds acting through distinct mechanisms during both the liver and the blood stages of the parasite life cycle. Compounds were designed on the basis of the "double-drug" approach: primaquine, which has been linked to statine-based inhibitors of plasmepsins (PLMs), the plasmodial aspartic proteases involved in degradation of hemeoglobin. The compounds were tested in vitro for anti-PLM I/PLM II activities and against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of P. falciparum. An antiplasmodial activity (IC50) as low as 0.1 mu M was obtained, an excellent improvement in comparison with inhibitors previously reported (IC50 = 2 - 20 mu M). The killing activity was equally directed against both P. falciparum strains and was correlated to lipophilicity (calculated as ALogP), for all compounds but one (9). All compounds inhibited PLM I and PLM II in the nanomolar range (K-i = 1 - 700 nM). The most promising compounds (2, 6, 10) were not cytotoxic against human fibroblasts at 100 mu M and were highly selective for PLMs vs human cathepsin D.