(2R,3S,4S,5R)-2.5-bis(N-Cbz-amino)-3,4-dihydroxy-1,6-di(4-fluorophenyl)hexane | 152929-93-6

• 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: (2R,3S,4S,5R)-2.5-bis(N-Cbz-amino)-3,4-dihydroxy-1,6-di(4-fluorophenyl)hexane
• 英文别名: benzyl N-[(2R,3S,4S,5R)-1,6-bis(4-fluorophenyl)-3,4-dihydroxy-5-(phenylmethoxycarbonylamino)hexan-2-yl]carbamate
• CAS: 152929-93-6
• 化学式: C₃₄H₃₄F₂N₂O₆
• 分子量: 604.651
• InChiKey: ASZCUOSYTCVMNZ-ZRTHHSRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  44
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S,5R)-2.5-bis(N-Cbz-amino)-3,4-dihydroxy-1,6-di(4-fluorophenyl)hexane 在 palladium dihydroxide sodium hydride 、 N,N-二异丙基乙胺 、 环己烯 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (4R,5S,6S,7R)-4,7-Bis-(4-fluoro-benzyl)-1,3-bis-(4-hydroxymethyl-benzyl)-5,6-bis-(2-trimethylsilanyl-ethoxymethoxy)-[1,3]diazepan-2-one
  参考文献：
  名称：

  Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors

  摘要：

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.

  DOI：

  10.1021/jm960083n
• 作为产物：
  描述：

  [(R)-2-(4-Fluoro-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid benzyl ester 在 lithium aluminium tetrahydride 、 [VCl3(thf)3] 、 铜 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (2R,3S,4S,5R)-2.5-bis(N-Cbz-amino)-3,4-dihydroxy-1,6-di(4-fluorophenyl)hexane
  参考文献：
  名称：

  Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors

  摘要：

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.

  DOI：

  10.1021/jm960083n

文献信息

• Substituted cyclic carbonyls and derivatives thereof useful as
  申请人：The Du Pont Merck Pharmaceutical Company

  公开号：US05610294A1

  公开（公告）日：1997-03-11

  This invention relates to substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors, to pharmaceutical compositions comprising such compounds, and to methods of using these compounds for treating viral infection. A representative compound of the invention is the compound of formula: ##STR1## wherein R.sup.22 and R.sup.23 are allyl.

  这项发明涉及用作逆转录病毒蛋白酶抑制剂的取代环状羰基化合物及其衍生物，涉及包含这些化合物的药物组合物，以及使用这些化合物治疗病毒感染的方法。该发明的代表性化合物是下式的化合物：其中R.sup.22和R.sup.23是丙烯基。
• Cyclic ureas and analogues useful as retroviral protease inhibitors
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0765873A1

  公开（公告）日：1997-04-02

  This invention relates to substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors, to pharmaceutical compositions comprising such compounds, and to methods of using these compounds for treating viral infection.

  本发明涉及可用作逆转录病毒蛋白酶抑制剂的取代环羰基及其衍生物、含有此类化合物的药物组合物以及使用这些化合物治疗病毒感染的方法。
• Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0858999A1

  公开（公告）日：1998-08-19

  This invention relates to substituted cyclic carbonyls and derivatives thereof useful as Human Immunodeficiency Virus (HIV) protease inhibitors, to pharmaceutical compositions comprising such compounds, and to methods of using these compounds for treating HIV infection.

  本发明涉及可用作人类免疫缺陷病毒（HIV）蛋白酶抑制剂的取代环羰基及其衍生物，涉及包含此类化合物的药物组合物，还涉及使用这些化合物治疗 HIV 感染的方法。
• CYCLIC UREAS AND ANALOGUES USEFUL AS RETROVIRAL PROTEASE INHIBITIORS
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0607334B1

  公开（公告）日：1997-07-30
• US5610294A
  申请人：——

  公开号：US5610294A

  公开（公告）日：1997-03-11