[ 2R-(2R*,3S*)]-N-t-Butyl-2-(3-amino-2-hydroxy-4-phenylbutyl)benzamide | 157309-35-8

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: [ 2R-(2R*,3S*)]-N-t-Butyl-2-(3-amino-2-hydroxy-4-phenylbutyl)benzamide
• 英文别名: 2-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-tert-butylbenzamide
• CAS: 157309-35-8
• 化学式: C₂₁H₂₈N₂O₂
• 分子量: 340.466
• InChiKey: NLXWAJFEFRLMRU-RBUKOAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [ 2R-(2R*,3S*)]-N-t-Butyl-2-(3-amino-2-hydroxy-4-phenylbutyl)benzamide 在 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-[(2R,3S)-3-((S)-2-Amino-3-benzylsulfanyl-propionylamino)-2-hydroxy-4-phenyl-butyl]-N-tert-butyl-benzamide
  参考文献：
  名称：

  Potent Human Immunodeficiency Virus Type 1 Protease Inhibitors That Utilize Noncoded d-Amino Acids as P₂/P₃ Ligands

  摘要：

  Noncoded D-amino acids have been designed to replace the quinaldic amide-asparaginyl moiety (P-2/P-3 ligand) found in several potent human immunodeficiency virus (HIV) protease inhibitors such as LY289612. The substituted nitrogen, optimally an N-methanesulfonyl moiety, served as a CH2CONH2 (asparagine side chain mimic), while the amino acid side chain became the backbone and P-3 ligand of these novel inhibitors. Compounds derived from S-aryl-D-cysteine proved to be patent HIV protease inhibitors which also exhibited potent whole cell antiviral activity. Oxidation of the cysteines to the sulfoxide or sulfone oxidation states resulted in significant improvements in potency. For example, the compound derived from N-(methylsulfonyl)-2-S-naphthylcysteine sulfone, 17c, was a 3.5 nM inhibitor of HIV protease which inhibited the spread of virus in MT4 cells with an IC50 = 4.3 nM. Compounds 17c,g,i were found to be orally bioavailable in a rat model.

  DOI：

  10.1021/jm950576c

文献信息

• Method of making HIV protease inhibitors
  申请人：——

  公开号：US20030216569A1

  公开（公告）日：2003-11-20

  A method of making HIV protease inhibitors of general formula ( 1 ): 1 These HIV compounds inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optically other antiviral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.

  一种制备一般式（1）的HIV蛋白酶抑制剂的方法：这些HIV化合物抑制或阻断HIV蛋白酶酶的生物活性，导致HIV病毒的复制终止。这些化合物以及含有这些化合物和其他光学抗病毒药物作为活性成分的药物组合物，适用于治疗感染HIV病毒的患者或宿主，HIV病毒已知会导致艾滋病。
• Inhibitors of HIV protease useful for the treatment of aids
  申请人：ELI LILLY AND COMPANY

  公开号：EP0604184A1

  公开（公告）日：1994-06-29

  The present invention provides novel HIV protease inhibitors, of formula I wherein: Zis hydrogen, formyl, carbamoyl, C2-C6 alkanoyl, C1-C4 alkoxycarbonyl, -C(O)CF3 or -S(O)2-R, where Ris C1-C6 alkyl, amino, trifluoromethyl, C1-C4 alkylamino, di(C1-C4)alkylamino, aryl, aryl(C1-C4)alkyl, heterocycle, unsaturated heterocycle or C5-C7 cycloalkyl; R1is aryl, C5-C7 cycloalkyl or -S-R1x, where R1x is aryl or C5-C7 cycloalkyl; R2is an amino acid side chain, -(CH2)y-X-R2a, cyano(C1-C4)alkyl or -(CH2)y-S(O)w-[1-N(R2c)-tetrazol-5-yl], where       y is 0, 1, 2 or 3;       X is a bond, divalent(C2-C4)alkenyl, divalent(C2-C4)alkynyl, -C(O)-O-, -O-C(O)-, -C(O)-NR2b-, -NR2b-C(O)-, -NR2b-, -C(O)-, -O-, -S(O)w-;       w is 0, 1 or 2;       R2a is C1-C6 alkyl, aryl, unsaturated heterocycle, heterocycle, aryl(C1-C4)alkyl, unsaturated heterocycle(C1-C4)alkyl or heterocycle(C1-C4)alkyl;       R2b is hydrogen or C1-C4 alkyl;       R2c is hydrogen, C1-C6 alkyl, aryl, unsaturated heterocycle, aryl(C1-C4)alkyl or unsaturated heterocycle(C1-C4)alkyl; Yis aryl or unsaturated heterocycle; R3is a group having the structure: where:       p is 4 or 5;       l is 3, 4 or 5;       R4 at each occurrence is independently hydrogen, C1-C6 alkyl or hydroxy(C1-C4)alkyl;       R5 and R6 are independently selected from hydrogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, amino, C1-C4 alkylamino, hydroxy(C1-C4)alkyl, carboxy, C1-C4 alkoxycarbonyl, carbamoyl, N-(C1-C4)alkylcarbamoyl, aryl, heterocycle or unsaturated heterocycle; with the proviso that when Z is hydrogen, formyl, carbamoyl, C2-C6 alkanoyl or C1-C4 alkoxycarbonyl; R2 is an amino acid side chain or -(CH2)y-X-R2a, where y is 0, 1, 2 or 3; X is a bond, -C(O)-O- or -C(O)-NR2b-; R2b is hydrogen; and R2a is aryl, heterocycle or unsaturated heterocycle; then R1 must be aryl or C5-C7 cycloalkyl; or a pharmaceutically acceptable salt thereof, pharmaceutical formulations containing those compounds and methods of treating and/or preventing HIV infection and/or AIDS.

  本发明提供了式 I 的新型 HIV 蛋白酶抑制剂 其中 Z是氢、甲酰基、氨基甲酰基、C2-C6烷酰基、C1-C4烷氧基羰基、-C(O)CF3或-S(O)2-R，其中 Ris C1-C6 烷基、氨基、三氟甲基、C1-C4 烷基氨基、二（C1-C4）烷基氨基、芳基、芳基（C1-C4）烷基、杂环、不饱和杂环或 C5-C7 环烷基； R1 是芳基、C5-C7 环烷基或-S-R1x，其中 R1x 是芳基或 C5-C7 环烷基； R2 是氨基酸侧链、-(CH2)y-X-R2a、氰基(C1-C4)烷基或-(CH2)y-S(O)w-[1-N(R2c)-四唑-5-基]，其中 y 是 0、1、2 或 3； X 是键、二价(C2-C4)烯基、二价(C2-C4)炔基、-C(O)-O-、-O-C(O)-、-C(O)-NR2b-、-NR2b-C(O)-、-NR2b-、-C(O)-、-O-、-S(O)w-； w 是 0、1 或 2； R2a 是 C1-C6 烷基、芳基、不饱和杂环、杂环、芳基（C1-C4）烷基、不饱和杂环（C1-C4）烷基或杂环（C1-C4）烷基； R2b 是氢或 C1-C4 烷基； R2c 是氢、C1-C6 烷基、芳基、不饱和杂环、芳基（C1-C4）烷基或不饱和杂环（C1-C4）烷基； Y 是芳基或不饱和杂环； R3 是具有以下结构的基团 其中 p 为 4 或 5； l 是 3、4 或 5； 每次出现的 R4 独立地为氢、C1-C6 烷基或羟基（C1-C4）烷基； R5 和 R6 独立选自氢、羟基、C1-C6 烷基、C1-C6 烷氧基、氨基、C1-C4 烷基氨基、羟基（C1-C4）烷基、羧基、C1-C4 烷氧基羰基、氨基甲酰基、N-（C1-C4）烷基氨基甲酰基、芳基、杂环或不饱和杂环； 但当 Z 为氢、甲酰基、氨基甲酰基、C2-C6 烷酰基或 C1-C4 烷氧基羰基时；R2 为氨基酸侧链或-(CH2)y-X-R2a，其中 y 为 0、1、2 或 3；X 为键、-C(O)-O-或-C(O)-NR2b-；R2b 为氢； R2a 是芳基、杂环或不饱和杂环； 则 R1 必须是芳基或 C5-C7 环烷基； 或其药学上可接受的盐、 含有这些化合物的药物制剂以及治疗和/或预防 HIV 感染和/或 AIDS 的方法。
• Inhibitors of HIV protease useful for the treatment of Aids
  申请人：ELI LILLY AND COMPANY

  公开号：EP0604182A2

  公开（公告）日：1994-06-29

  The present invention provides novel HIV protease inhibitors, pharmaceutical formulations containing those compounds and methods of treating and/or preventing HIV infection and/or AIDS.

  本发明提供了新型艾滋病毒蛋白酶抑制剂、含有这些化合物的药物制剂以及治疗和/或预防艾滋病毒感染和/或艾滋病的方法。
• Inhibitors of HIV protease useful for the treatment of AIDS
  申请人：ELI LILLY AND COMPANY

  公开号：EP0609625A1

  公开（公告）日：1994-08-10

  The present invention provides novel HIV protease inhibitors, pharmaceutical formulations containing those compounds and methods of treating and/or preventing HIV infection and/or AIDS.

  本发明提供了新型艾滋病毒蛋白酶抑制剂、含有这些化合物的药物制剂以及治疗和/或预防艾滋病毒感染和/或艾滋病的方法。
• Hiv protease inhibitors
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：EP1340744A2

  公开（公告）日：2003-09-03

  HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.

  可通过化学合成获得的艾滋病毒蛋白酶抑制剂可抑制或阻断艾滋病毒蛋白酶的生物活性，从而终止艾滋病毒的复制。这些化合物以及含有这些化合物和其他抗病毒剂作为活性成分的药物组合物，适用于治疗感染艾滋病毒的患者或宿主。