N-((S)-1-Carbamoyl-3-methyl-butyl)-2-mercapto-benzamide | 824938-52-5

• 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: N-((S)-1-Carbamoyl-3-methyl-butyl)-2-mercapto-benzamide
• 英文别名: N-(2-Mercaptobenzoyl)-L-leucine；N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-2-sulfanylbenzamide
• CAS: 824938-52-5
• 化学式: C₁₃H₁₈N₂O₂S
• 分子量: 266.364
• InChiKey: OOAHVPGYSPSYLR-JTQLQIEISA-N

物化性质

• 沸点：
  493.3±30.0 °C(Predicted)
• 密度：
  1.176±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  73.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-((S)-1-Carbamoyl-3-methyl-butyl)-2-mercapto-benzamide 以 N,N-二甲基乙酰胺 为溶剂， 生成 1-{4-[2-((S)-1-Carbamoyl-3-methyl-butylcarbamoyl)-phenylsulfanylcarbonyl]-butyl}-pyridinium; bromide
  参考文献：
  名称：

  Synthesis and Biological Properties of Amino Acid Amide Ligand-Based Pyridinioalkanoyl Thioesters as Anti-HIV Agents

  摘要：

  Hyper-mutable retroviruses such as HIV can become rapidly resistant to drugs used to treat infection, Strategies for coping with drug-resistant strains of virus include combination therapies. using viral protease and reverse transcriptase inhibitors. Another approach is the development of antiviral agents that attack mutationally nonpermissive targets that have functions essential for viral replication. Thus, the highly conserved nucleocapsid protein. NCp7, was chosen as a prime target in our search for novel anti-HIV agents that can overcome the problem of viral drug resistance. Recently, we reported (J. Med. Chem. 1999 42, 67) a novel chemotype, the pyridinioalkanoyl thioesters (PATEs), based on 2-mercaptobenzamides as the thiol component and having its amide nitrogen substituted with various phenylsulfonyl moieties. These compounds were identified as relatively nontoxic anti-HIV agents in the XTT cytoprotection assay. In this study. we wish to report a separate genre of active PATEs wherein the thiol component consists of an N-2-mercaptobenzoyl-amino acid derivative. Active derivatives (EC50 < 10 muM) reported herein were confined to amino acid primary amides or methyl amides having side chains no larger than isobutyl. Amino acids terminating in free carboxyl or carboxylic acid ester groups were mostly inactive. Selected compounds were shown to be active on chronically infected CEM/SK-1, TNFalpha-induced U1. ACH-2 cells and virucidal on cell-free virus, latently infected U I cells and acutely infected primary peripheral blood mononuclear cells (PBMCs). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00392-3
• 作为产物：
  描述：

  2, 2'-二硫代二苯甲酸 在 N-甲基吗啉 、 氯化亚砜 、 tris(carboxyethyl)phosphine hydrochloride 、 三乙胺 作用下， 以 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-((S)-1-Carbamoyl-3-methyl-butyl)-2-mercapto-benzamide
  参考文献：
  名称：

  Synthesis and Biological Properties of Amino Acid Amide Ligand-Based Pyridinioalkanoyl Thioesters as Anti-HIV Agents

  摘要：

  Hyper-mutable retroviruses such as HIV can become rapidly resistant to drugs used to treat infection, Strategies for coping with drug-resistant strains of virus include combination therapies. using viral protease and reverse transcriptase inhibitors. Another approach is the development of antiviral agents that attack mutationally nonpermissive targets that have functions essential for viral replication. Thus, the highly conserved nucleocapsid protein. NCp7, was chosen as a prime target in our search for novel anti-HIV agents that can overcome the problem of viral drug resistance. Recently, we reported (J. Med. Chem. 1999 42, 67) a novel chemotype, the pyridinioalkanoyl thioesters (PATEs), based on 2-mercaptobenzamides as the thiol component and having its amide nitrogen substituted with various phenylsulfonyl moieties. These compounds were identified as relatively nontoxic anti-HIV agents in the XTT cytoprotection assay. In this study. we wish to report a separate genre of active PATEs wherein the thiol component consists of an N-2-mercaptobenzoyl-amino acid derivative. Active derivatives (EC50 < 10 muM) reported herein were confined to amino acid primary amides or methyl amides having side chains no larger than isobutyl. Amino acids terminating in free carboxyl or carboxylic acid ester groups were mostly inactive. Selected compounds were shown to be active on chronically infected CEM/SK-1, TNFalpha-induced U1. ACH-2 cells and virucidal on cell-free virus, latently infected U I cells and acutely infected primary peripheral blood mononuclear cells (PBMCs). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00392-3

文献信息

• Optimization of unique, uncharged thioesters as inhibitors of HIV replication
  作者：Pratibha Srivastava、Marco Schito、Rasem J. Fattah、Toshiaki Hara、Tracy Hartman、Robert W. Buckheit、Jim A. Turpin、John K. Inman、Ettore Appella

  DOI：10.1016/j.bmc.2004.09.032

  日期：2004.12

  A combinatorial chemistry approach was employed to prepare a restricted library of N-substituted S-acyl-2-mercapto-benzamide thioesters. It was shown that many members of this chemotype display anti-HIV activity via their ability to interact with HIV-1, HIV-2, SIV-infected cells, cell-free virus, and chronically and latently infected cells in a manner consistent with targeting of the highly conserved HIV-1 NCp7 zinc fingers. Compounds were initially screened using two different in vitro antiviral assays and evaluated for stability in neutral buffer containing 10% pooled human Serum using a spectrophotometric assay. These data revealed that there was no significant correlation between thioester stability and antiviral activity, however, a slight inverse correlation between serum stability and virucidal activity was noted. Based on the virucidal capability and the ability to select lead compounds to inhibit virus expression from latently infected TNFalpha-induced U1 cells, we next determined if these compounds could prevent HIV cell-to-cell transmission. Several thioesters demonstrated potent inhibition of HIV cell-to-cell transmission with EC50 values in the 80-100 nM range. Thus, we have optimized a series of restricted thioesters and provided evidence that serum stability is not required for antiviral activity. Moreover, selected compounds show potential for development as topical microbicides. (C) 2004 Elsevier Ltd. All rights reserved.
• A one-pot preparation of N-2-mercaptobenzoyl-amino amides
  作者：Robert J. Bahde、Daniel H. Appella、William C. Trenkle

  DOI：10.1016/j.tetlet.2011.05.115

  日期：2011.8

  The HIV-1 nucleocapsid (NCp7), structurally defined by zinc-binding domains, participates in crucial stages of the HIV-1 lifecycle and is mutationally nonpermissive, making it an attractive anti-HIV target. Mode of action studies have shown that the secondary structure and activity of NCp7 can be disrupted by acyl transfer from N-2-mercaptobenzoyl-amino amides. We have developed an improved one-pot reaction that affords N-2-mercaptobenzoyl-amino acids on multi-gram scales. This synthetic route allows for rapid modular construction and has greatly expanded the scope of easily accessible potential NCp7 inhibitors. Published by Elsevier Ltd.
• Synthesis and Biological Properties of Amino Acid Amide Ligand-Based Pyridinioalkanoyl Thioesters as Anti-HIV Agents
  作者：Yongsheng Song、Atul Goel、Venkatesha Basrur、Paula E.A Roberts、Judy A Mikovits、John K Inman、Jim A Turpin、William G Rice、Ettore Appella

  DOI：10.1016/s0968-0896(01)00392-3

  日期：2002.5

  Hyper-mutable retroviruses such as HIV can become rapidly resistant to drugs used to treat infection, Strategies for coping with drug-resistant strains of virus include combination therapies. using viral protease and reverse transcriptase inhibitors. Another approach is the development of antiviral agents that attack mutationally nonpermissive targets that have functions essential for viral replication. Thus, the highly conserved nucleocapsid protein. NCp7, was chosen as a prime target in our search for novel anti-HIV agents that can overcome the problem of viral drug resistance. Recently, we reported (J. Med. Chem. 1999 42, 67) a novel chemotype, the pyridinioalkanoyl thioesters (PATEs), based on 2-mercaptobenzamides as the thiol component and having its amide nitrogen substituted with various phenylsulfonyl moieties. These compounds were identified as relatively nontoxic anti-HIV agents in the XTT cytoprotection assay. In this study. we wish to report a separate genre of active PATEs wherein the thiol component consists of an N-2-mercaptobenzoyl-amino acid derivative. Active derivatives (EC50 < 10 muM) reported herein were confined to amino acid primary amides or methyl amides having side chains no larger than isobutyl. Amino acids terminating in free carboxyl or carboxylic acid ester groups were mostly inactive. Selected compounds were shown to be active on chronically infected CEM/SK-1, TNFalpha-induced U1. ACH-2 cells and virucidal on cell-free virus, latently infected U I cells and acutely infected primary peripheral blood mononuclear cells (PBMCs). (C) 2002 Elsevier Science Ltd. All rights reserved.