methyl-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid | 156408-36-5

• 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: methyl-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
• CAS: 156408-36-5
• 化学式: C₁₇H₂₀NO₄P
• 分子量: 333.324
• InChiKey: FAAFALMMECAALB-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Antibody-Catalyzed Hydrolysis of an Unsubstituted Amide

  摘要：

  The generation of antibodies capable of catalyzing the unassisted hydrolysis of unactivated amides has been an enduring goal of research in the field. Antidialkylphosphinate 1 monoclonal antibodies were screened for their ability to catalyze the hydrolysis of four methyl esters and four primary amides at pH 5.0, 7.0, and 9.0. One of 68 antibodies, 13D11, enantiospecifically hydrolyzed the C-terminal carboxamide of a dansyl-alkylated derivative of (R)-phenylalaninamide (2b). At pH 9.0, 13D11 catalyzed amide hydrolysis with a k(cat) of 1.65 X 10(-7) s(-1) and a K-m of 432 mu M and was stereospecifically inhibited by hapten with a K-i of 14.0 mu M. A shorter, acetylated derivative 3b was not hydrolyzed by 13D11, demonstrating that dansyl-alkyl binding interactions are essential for catalysis. Equally active antibody preparations were obtained from two separate batches of ascites. The antibody Fab' fragment was prepared, purified, and found to retain full activity. Amidolytic activity was not abolished by any of nine inhibitors of natural proteolytic enzymes. The rate of uncatalyzed amide hydrolysis was experimentally determined to be 1.25 x 10(-9) s(-1), indicating an antibody catalytic rate enhancement (k(cat)/k(uncat)) of 132.

  DOI：

  10.1021/ja00094a003
• 作为产物：
  描述：

  Carbamic acid, [1-(methoxyphosphinyl)-2-phenylethyl]-, phenylmethylester, (1R)- 在 lithium hydroxide 、 sodium hydride 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 51.5h， 生成 methyl-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
  参考文献：
  名称：

  Antibody-Catalyzed Hydrolysis of an Unsubstituted Amide

  摘要：

  The generation of antibodies capable of catalyzing the unassisted hydrolysis of unactivated amides has been an enduring goal of research in the field. Antidialkylphosphinate 1 monoclonal antibodies were screened for their ability to catalyze the hydrolysis of four methyl esters and four primary amides at pH 5.0, 7.0, and 9.0. One of 68 antibodies, 13D11, enantiospecifically hydrolyzed the C-terminal carboxamide of a dansyl-alkylated derivative of (R)-phenylalaninamide (2b). At pH 9.0, 13D11 catalyzed amide hydrolysis with a k(cat) of 1.65 X 10(-7) s(-1) and a K-m of 432 mu M and was stereospecifically inhibited by hapten with a K-i of 14.0 mu M. A shorter, acetylated derivative 3b was not hydrolyzed by 13D11, demonstrating that dansyl-alkyl binding interactions are essential for catalysis. Equally active antibody preparations were obtained from two separate batches of ascites. The antibody Fab' fragment was prepared, purified, and found to retain full activity. Amidolytic activity was not abolished by any of nine inhibitors of natural proteolytic enzymes. The rate of uncatalyzed amide hydrolysis was experimentally determined to be 1.25 x 10(-9) s(-1), indicating an antibody catalytic rate enhancement (k(cat)/k(uncat)) of 132.

  DOI：

  10.1021/ja00094a003

文献信息

• HIV protease inhibitors useful for the treatment of aids
  申请人：MERCK & CO. INC.

  公开号：EP0337714A2

  公开（公告）日：1989-10-18

  Compounds of the form wherein A is an amine protecting group commonly employed in peptide synthesis, G a dipeptide isostere, B an amino acid or analog thereof, and J a small terminal group are described. These compounds are useful in the inhibition of HIV protease, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  描述了以下形式的化合物 其中 A 是肽合成中常用的胺保护基团，G 是二肽异构体，B 是氨基酸或其类似物，J 是小末端基团。这些化合物作为化合物、药学上可接受的盐、药物组合成分，无论是否与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用，都可用于抑制 HIV 蛋白酶、预防或治疗 HIV 感染以及治疗 AIDS。还描述了治疗艾滋病的方法和预防或治疗艾滋病毒感染的方法。
• Antibody-Catalyzed Hydrolysis of an Unsubstituted Amide
  作者：Mark T. Martin、Thelma S. Angeles、Renee Sugasawara、Nurredin I. Aman、Andrew D. Napper、Michael J. Darsley、Rosa I. Sanchez、Paul Booth、Richard C. Titmas

  DOI：10.1021/ja00094a003

  日期：1994.7

  The generation of antibodies capable of catalyzing the unassisted hydrolysis of unactivated amides has been an enduring goal of research in the field. Antidialkylphosphinate 1 monoclonal antibodies were screened for their ability to catalyze the hydrolysis of four methyl esters and four primary amides at pH 5.0, 7.0, and 9.0. One of 68 antibodies, 13D11, enantiospecifically hydrolyzed the C-terminal carboxamide of a dansyl-alkylated derivative of (R)-phenylalaninamide (2b). At pH 9.0, 13D11 catalyzed amide hydrolysis with a k(cat) of 1.65 X 10(-7) s(-1) and a K-m of 432 mu M and was stereospecifically inhibited by hapten with a K-i of 14.0 mu M. A shorter, acetylated derivative 3b was not hydrolyzed by 13D11, demonstrating that dansyl-alkyl binding interactions are essential for catalysis. Equally active antibody preparations were obtained from two separate batches of ascites. The antibody Fab' fragment was prepared, purified, and found to retain full activity. Amidolytic activity was not abolished by any of nine inhibitors of natural proteolytic enzymes. The rate of uncatalyzed amide hydrolysis was experimentally determined to be 1.25 x 10(-9) s(-1), indicating an antibody catalytic rate enhancement (k(cat)/k(uncat)) of 132.