(4R)-3-[(2S,3S)-3-[(3-amino-2-chloro-benzoyl)amino]-2-hydroxy-4-(4-methoxyphenyl)butanoyl]-N-[(2,6-dimethylphenyl)methyl]-5,5-dimethyl-thiazolidine-4-carboxamide | 345666-32-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (4R)-3-[(2S,3S)-3-[(3-amino-2-chloro-benzoyl)amino]-2-hydroxy-4-(4-methoxyphenyl)butanoyl]-N-[(2,6-dimethylphenyl)methyl]-5,5-dimethyl-thiazolidine-4-carboxamide
• 英文别名: (4R)-3-[(2S,3S)-3-[(3-amino-2-chlorobenzoyl)amino]-2-hydroxy-4-(4-methoxyphenyl)butanoyl]-N-[(2,6-dimethylphenyl)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• CAS: 345666-32-2
• 化学式: C₃₃H₃₉ClN₄O₅S
• 分子量: 639.215
• InChiKey: KRNYNRYZARNPTH-PIZZNKLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氨基-2-氯苯甲酸 、 (R)-N-(2,6-dimethylbenzyl)-3-[(2S,3S)-3-amino-2-hydroxy-4-(4-methoxyphenyl)butanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (4R)-3-[(2S,3S)-3-[(3-amino-2-chloro-benzoyl)amino]-2-hydroxy-4-(4-methoxyphenyl)butanoyl]-N-[(2,6-dimethylphenyl)methyl]-5,5-dimethyl-thiazolidine-4-carboxamide
  参考文献：
  名称：

  新型的HIV-1蛋白酶抑制剂含有3-氨基-2-氯苯甲酰基-allophenylnorstatine结构的构效关系。

  摘要：

  设计并合成了一系列含有取代的别苯基去甲他汀（Apns：（2S，3S）-3-氨基-2-羟基-4-羟基丁酸）的拟肽类人免疫缺陷病毒（HIV）蛋白酶抑制剂。从该系列化合物的构效关系，发现SM-309515对野生型和抗性HIV-1具有有效的抗病毒活性，并在犬中具有理想的药代动力学特征。

  DOI：

  10.1016/j.bmc.2007.10.062

文献信息

• Novel dipeptide compounds and their use as medicines
  申请人：——

  公开号：US20020049165A1

  公开（公告）日：2002-04-25

  A novel dipeptide compound inhibiting the enzymatic activity of HIV protease, an anti-AIDS medicine comprising this dipeptide compound as an effective component. The dipeptide compound is the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof 1 wherein R 1 , R 2 , and R 3 independently represent a linear or branched, saturated or unsaturated lower alkyl group, alkoxyl group, alkyl amino group, or dialkyl amino group having 1-4 carbon atoms (with a carbon atom being either replaced by an oxygen atom or not), a halogeno group, or a hydrogen atom, provided that all of the R 1 , R 2 , and R 2 are not a hydrogen atom at the same time, R 2 and R 3 may form a ring together, R 4 represents a linear or branched lower alkyl group having 1-4 carbon atoms or a hydrogen atom; X is a methylene group or a sulfur atom; Y represents a five or six member monocyclic or polycyclic hydrocarbon group, a heterocyclic group having a structure in which one or more carbon atom in the monocyclic or polycyclic hydrocarbon group is replaced by a hetero atom, an aryloxy group having 12 or less carbon atoms, in which the aromatic ring may be substituted with an alkyl group, alkoxy group, halogeno group, amino group or hydroxyl group; and Z represents an aliphatic hydrocarbon group having 1-6 carbon atoms or an aromatic hydrocarbon group having 12 or less carbon atoms in which the aromatic ring may be substituted with an alkyl group, alkoxy group, or halogeno group, or one or more carbon atom in the aromatic hydrocarbon group may be replaced by a hetero atom.

  一种新型二肽化合物，能够抑制HIV蛋白酶的酶活性，一种抗艾滋病药物，其中包括该二肽化合物作为有效成分。该二肽化合物是由式(I)表示的化合物或其药学上可接受的盐，其中R1、R2和R3独立地表示线性或支链、饱和或不饱和的低碳基、烷氧基、烷基氨基或二烷基氨基，其碳原子数为1-4个（其中一个碳原子被氧原子替换或未被替换），卤素基或氢原子，前提是R1、R2和R3不能同时为氢原子，R2和R3可以一起形成环，R4表示线性或支链低碳基或氢原子；X表示亚甲基基团或硫原子；Y表示五元或六元单环或多环烃基，具有一种结构，其中单环或多环烃基中的一个或多个碳原子被杂原子取代，具有12个或更少碳原子的芳氧基，其中芳环可以用烷基、烷氧基、卤素基、氨基或羟基取代；Z表示具有1-6个碳原子的脂肪烃基或具有12个或更少碳原子的芳香烃基，其中芳环可以用烷基、烷氧基或卤素基取代，或者芳香烃基中的一个或多个碳原子可以被杂原子取代。
• NOVEL DIPEPTIDE COMPOUND AND MEDICINAL USE THEREOF
  申请人：JAPAN ENERGY CORPORATION

  公开号：EP1157997A1

  公开（公告）日：2001-11-28

  A novel dipeptide compound inhibiting the enzymatic activity of HIV protease, an anti-AIDS medicine comprising this dipeptide compound as an effective component. The dipeptide compound is the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof wherein R1, R2, and R3 independently represent a linear or branched, saturated or unsaturated lower alkyl group, alkoxyl group, alkyl amino group, or dialkyl amino group having 1-4 carbon atoms (with a carbon atom being either replaced by an oxygen atom or not), a halogeno group, or a hydrogen atom, provided that all of the R1, R2, and R3 are not a hydrogen atom at the same time, R2 and R3 may form a ring together, R4 represents a linear or branched lower alkyl group having 1-4 carbon atoms or a hydrogen atom; X is a methylene group or a sulfur atom; Y represents a five or six member monocyclic or polycyclic hydrocarbon group, a heterocyclic group having a structure in which one or more carbon atom in the monocyclic or polycyclic hydrocarbon group is replaced by a hetero atom, an aryloxy group having 12 or less carbon atoms, in which the aromatic ring may be substituted with an alkyl group, alkoxy group, halogeno group, amino group or hydroxyl group; and Z represents an aliphatic hydrocarbon group having 1-6 carbon atoms or an aromatic hydrocarbon group having 12 or less carbon atoms in which the aromatic ring may be substituted with an alkyl group, alkoxy group, or halogeno group, or one or more carbon atom in the" aromatic hydrocarbon group may be replaced by a hetero atom.

  一种抑制 HIV 蛋白酶酶活性的新型二肽化合物，一种以该二肽化合物为有效成分的抗艾滋病药物。该二肽化合物是式 (I) 所代表的化合物或其药学上可接受的盐 其中 R1、R2 和 R3 独立地代表具有 1-4 个碳原子的直链或支链、饱和或不饱和低级烷基、烷氧基、烷基氨基或具有 1-4 个碳原子的二烷基氨基（碳原子可以被氧原子取代，也可以不被氧原子取代）、卤素基团或氢原子，条件是所有的 R1、R2 和 R3 不是同时为氢原子，R2 和 R3 可以一起形成一个环，R4 代表具有 1-4 个碳原子的直链或支链低级烷基或氢原子；X 是亚甲基或硫原子；Y 代表五元或六元单环或多环烃基、杂环基（其结构中单环或多环烃基的一个或多个碳原子被杂原子取代）、芳氧基（具有 12 个或更少碳原子），其中芳环可被烷基、烷氧基、卤素基、氨基或羟基取代；Z 代表具有 1-6 个碳原子的脂肪族烃基或具有 12 个或更少碳原子的芳香族烃基，其中芳香环可被烷基、烷氧基或卤代基团取代，或 "芳香族烃基 "中的一个或多个碳原子可被杂原子取代。
• US6673772B2
  申请人：——

  公开号：US6673772B2

  公开（公告）日：2004-01-06
• Structure–activity relationships of novel HIV-1 protease inhibitors containing the 3-amino-2-chlorobenzoyl-allophenylnorstatine structure
  作者：Tsutomu Mimoto、Satoshi Nojima、Keisuke Terashima、Haruo Takaku、Makoto Shintani、Hideya Hayashi

  DOI：10.1016/j.bmc.2007.10.062

  日期：2008.2.1

  A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenylnorstatine (Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid) were designed and synthesized. From the structure-activity relationship of this series of compounds, SM-309515 was found to have potent antiviral activity against wild-type and resistant HIV-1s and to possess a desirable

  设计并合成了一系列含有取代的别苯基去甲他汀（Apns：（2S，3S）-3-氨基-2-羟基-4-羟基丁酸）的拟肽类人免疫缺陷病毒（HIV）蛋白酶抑制剂。从该系列化合物的构效关系，发现SM-309515对野生型和抗性HIV-1具有有效的抗病毒活性，并在犬中具有理想的药代动力学特征。