tert-butyl N-[[4-(diethylamino)phenyl]methyl-[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]amino]carbamate | 202586-19-4

• 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: tert-butyl N-[[4-(diethylamino)phenyl]methyl-[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]amino]carbamate
• CAS: 202586-19-4
• 化学式: C₂₈H₃₉F₃N₄O₄
• 分子量: 552.637
• InChiKey: TWRVGPBDXFZXDO-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  94.1
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[[4-(diethylamino)phenyl]methyl-[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]amino]carbamate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以90%的产率得到1-[p-(N,N-diethylamino)-phenyl]-4(S)-hydroxy-2-(tert-butyloxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane
  参考文献：
  名称：

  New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development

  摘要：

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

  DOI：

  10.1021/jm970873c
• 作为产物：
  描述：

  N,N-二乙基-4-氨基苯甲醛 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 20.0h， 生成 tert-butyl N-[[4-(diethylamino)phenyl]methyl-[(2S,3S)-2-hydroxy-4-phenyl-3-[(2,2,2-trifluoroacetyl)amino]butyl]amino]carbamate
  参考文献：
  名称：

  New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development

  摘要：

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.

  DOI：

  10.1021/jm970873c

文献信息

• ANILINOPEPTIDE DERIVATIVES
  申请人：Novartis AG

  公开号：EP0915841A1

  公开（公告）日：1999-05-19
• US6451973B1
  申请人：——

  公开号：US6451973B1

  公开（公告）日：2002-09-17
• [EN] ANILINOPEPTIDE DERIVATIVES<br/>[FR] DERIVES D'ANILINOPEPTIDE
  申请人：NOVARTIS AG

  公开号：WO1998003476A1

  公开（公告）日：1998-01-29

  (EN) The invention relates to compounds of formula (I), in which R1 and R2 are, independently of each other, lower alkyl or lower alkoxy-lower alkyl; R3 and R4 are, independently of each other, sec-lower alkyl or tert-lower alkyl; R5 is phenyl or cyclohexyl; and R6 and R7 are, independently of each other, lower alkyl, or, together with the linking nitrogen atom, pyrrolidino, piperidino, 4-lower alkylpiperidino, 1,2,4-triazol-1-yl or 1,2,4-triazol-4-yl; or a salt thereof, provided that at least one salt-forming group is present. These compounds are inhibitors of HIV protease and are therefore suitable, for example, for treating AIDS or its preliminary stages.(FR) Cette invention concerne des composés correspondant à la formule (I) où R1 et R2 représentent indépendamment l'un de l'autre, alkyle inférieur ou alcoxy inférieur-alkyle inférieur. R3 et R4 représentent indépendamment l'un de l'autre un alkyle inférieur sec. ou un alkyle inférieur tert., tandis que R5 représente phényle ou cyclohexyle. R6 et R7 représentent enfin, et indépendamment l'un de l'autre, un alkyle inférieur. Lorsqu'ils sont associés à l'atome d'azote de liaison, R6 et R7 peuvent également représenter pyrrolidino, pipéridino, alkylpipéridino 4 inférieur, 1,2,4-triazol-1-yl ou 1,2,4-triazol-4-yl. Cette invention concerne également les sels de ces composés, étant entendu qu'un groupe au moins de formation de sel est présent. Ces composés consistent en des inhibiteurs de protéase de VIH, et peuvent ainsi être utilisés, par exemple, dans le traitement du SIDA ou de ses stades préliminaires.
• New Aza-Dipeptide Analogues as Potent and Orally Absorbed HIV-1 Protease Inhibitors:  Candidates for Clinical Development
  作者：Guido Bold、Alexander Fässler、Hans-Georg Capraro、Robert Cozens、Thomas Klimkait、Janis Lazdins、Jürgen Mestan、Bernard Poncioni、Johannes Rösel、David Stover、Marina Tintelnot-Blomley、Figan Acemoglu、Werner Beck、Eugen Boss、Martin Eschbach、Thomas Hürlimann、Elvira Masso、Serge Roussel、Katharina Ucci-Stoll、Dominique Wyss、Marc Lang

  DOI：10.1021/jm970873c

  日期：1998.8.1

  On the basis of previously described X-ray studies of an enzyme/aza-dipeptide complex,(8) azadipeptide analogues carrying N-(bis-aryl-methyl) substituents on the (hydroxethyl)hydrazine moiety have been designed and synthesized as HIV-1 protease inhibitors. By using either equally (12) ororthogonally (13) protected dipeptide isosteres, symmetrically and asymmetrically acylated aza-dipeptides can be synthesized. This approach led to the discovery of very potent inhibitors with antiviral activities (ED50) in the subnanomolar range. Acylation of the (hydroxethyl)hydrazine dipeptide isostere with the L-tert-leucine derivative 29 increased the oral bioavailability significantly when compared to the corresponding L-valine or L-isoleucine derivatives. The bis(L-tert-leucine) derivatives CGP 75355, CGP 73547, CGP 75136, and CGP 75176 combine excellent antiviral activity with high blood concentration after oral administration. Furthermore, they show no cross-resistance with saquinavir-resistant strains and maintain activity against indinavir-resistant ones. Consequently they qualify for further profiling as potential clinical candidates.