Carbamic acid, [1-(methoxyphosphinyl)-2-phenylethyl]-, phenylmethylester, (1R)- | 129312-69-2

• 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: Carbamic acid, [1-(methoxyphosphinyl)-2-phenylethyl]-, phenylmethylester, (1R)-
• 英文别名: P(R,S)-2-Phenyl-1(R)-[(phenylmethoxy)carbonyl]aminoethyl phosphinic acid methyl ester
• CAS: 129312-69-2；174850-07-8；174850-08-9
• 化学式: C₁₇H₂₀NO₄P
• 分子量: 333.324
• InChiKey: KXLBSEMTSLRFRE-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

文献信息

• 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.
• Design and synthesis of phosphinic acids that triply inhibit endothelin converting enzyme, angiotensin converting enzyme and neutral endopeptidase 24.11
  作者：Brian A. McKittrick、Andrew W. Stamford、Xiaoyu Weng、Ke Ma、Samuel Chackalamannil、Michael Czarniecki、ReneéM. Cleven、Ahmad B. Fawzi

  DOI：10.1016/0960-894x(96)00297-1

  日期：1996.7

  We have synthesized a series of phosphinic acids as inhibitors of a metalloprotease endothelin converting enzyme (ECE). Potent ECE inhibitors 4g and 4o were identified. These compounds are members of a novel class of ECE inhibitors that are also potent inhibitors of angiotensin converting enzyme and neutral endopeptidase. Copyright (C) 1996 Elsevier Science Ltd
• Transition State Analogy of Phosphonic Acid Peptide Inhibitors of Pepsin
  作者：Paul A. Bartlett、Mark A. Giangiordano

  DOI：10.1021/jo952074c

  日期：1996.1.1

  A series of 11 phosphonate peptide analogs, RO(2)C-Xaa-Yaa-Phe-(PO2--O)-Phe O-(3-(4-pyridyl)propyl ester), were synthesized and evaluated as inhibitors of the aspartic peptidase pepsin. For the inhibitors with Gly or Ala at the P-2 position, the K-i values correlate with the K-m/k(cat) values of the corresponding substrates, demonstrating that these analogs mimic the transition state in the way the P-2-P-4 residues bind. Deviations from the correlation for the other inhibitor/substrate pairs imply a different binding orientation as a result of N-substitution at P-2 (Pro), contamination with the more potent diastereomer (D-Ala), or a change in rate-limiting step for turnover (lie).
• PHOSPHINIC ACID DERIVATIVES
  申请人：SCHERING CORPORATION

  公开号：EP0767794B1

  公开（公告）日：2000-02-02
• US5476847A
  申请人：——

  公开号：US5476847A

  公开（公告）日：1995-12-19