N-tert-butoxycarbonyl-L-3-(1-naphthyl)alanine-N-methylamide | 188728-76-9

• 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-tert-butoxycarbonyl-L-3-(1-naphthyl)alanine-N-methylamide
• 英文别名: tert-butyl N-[(2S)-1-(methylamino)-3-naphthalen-1-yl-1-oxopropan-2-yl]carbamate
• CAS: 188728-76-9
• 化学式: C₁₉H₂₄N₂O₃
• 分子量: 328.411
• InChiKey: QJSGDFZQDAETNZ-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-L-3-(1-naphthyl)alanine-N-methylamide 在 三氟乙酸 作用下， 反应 0.5h， 生成 (S)-2-amino-N-methyl-3-(naphthalen-1-yl)propanamide
  参考文献：
  名称：

  Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors

  摘要：

  The synthesis and biological evaluation of orally active inhibitors of matrix metalloproteinase are reported. Modifications of the P2' position and the a-substituent of hydroxamic acid derivatives were carried out, and revealed that the P2' substituent influenced the MMP inhibitory activities in vitro and in plasma after oral administration. The hydroxamates with phenylglycine at the P2' position were absorbed well orally. Compound 15e, which exhibited the longest duration of inhibitory activity in plasma after oral administration among the phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant arthritis model. A reduction in hind foot pad swelling and improvements of some inflammatory parameters were demonstrated when the compound was administered orally. These results indicate the potential of MMP inhibitors for rheumatoid arthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00028-x
• 作为产物：
  描述：

  Boc-3-(1-萘基)-L-丙氨酸 、 盐酸甲胺 在 N,N'-羰基二咪唑 作用下， 生成 N-tert-butoxycarbonyl-L-3-(1-naphthyl)alanine-N-methylamide
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study

  摘要：

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

  DOI：

  10.1021/jm970494j

文献信息

• Fas LIGAND SOLUBILIZATION INHIBITOR
  申请人：KANEBO LTD.

  公开号：EP0848957A1

  公开（公告）日：1998-06-24

  A Fas ligand solubilization inhibitor which comprises, as the active ingredient, a compound of the generic formula (I) having a matrix metalloproteinase inhibitory activity or its pharmaceutically acceptable salt. The drug is useful in the prevention or treatment of diseases caused by solubilized Fas ligand, such as hepatitis, GVHD, AIDS, autoimmune diseases, etc.

  一种Fas配体溶解抑制剂，其活性成分为具有基本结构式（I）的化合物，具有基质金属蛋白酶抑制活性或其药用盐。该药物可用于预防或治疗由溶解的Fas配体引起的疾病，如肝炎、移植物抗宿主病、艾滋病、自身免疫疾病等。
• 一种PIN1抑制剂及其在制备药物中的用途
  申请人：成都先导药物开发股份有限公司

  公开号：CN118063464A

  公开（公告）日：2024-05-24

  本发明公开了一种抑制剂，具体涉及一类PIN1抑制剂以及在制备药物中的用途。本发明公开了式I所示的化合物、或其立体异构体在制备抑制PIN1类药物中的用途，为临床上筛选和/或制备与PIN1活性相关的疾病的药物提供了一种新的选择。#imgabs0#
• Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study
  作者：Daniel E. Levy、France Lapierre、Weisheng Liang、Wenqing Ye、Christopher W. Lange、Xiaoyuan Li、Damian Grobelny、Marie Casabonne、David Tyrrell、Kevin Holme、Alex Nadzan、Richard E. Galardy

  DOI：10.1021/jm970494j

  日期：1998.1.1

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.
• Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors
  作者：Ryoichi Hirayama、Minoru Yamamoto、Takahiro Tsukida、Konomi Matsuo、Yuji Obata、Fumio Sakamoto、Shoji Ikeda

  DOI：10.1016/s0968-0896(97)00028-x

  日期：1997.4

  The synthesis and biological evaluation of orally active inhibitors of matrix metalloproteinase are reported. Modifications of the P2' position and the a-substituent of hydroxamic acid derivatives were carried out, and revealed that the P2' substituent influenced the MMP inhibitory activities in vitro and in plasma after oral administration. The hydroxamates with phenylglycine at the P2' position were absorbed well orally. Compound 15e, which exhibited the longest duration of inhibitory activity in plasma after oral administration among the phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant arthritis model. A reduction in hind foot pad swelling and improvements of some inflammatory parameters were demonstrated when the compound was administered orally. These results indicate the potential of MMP inhibitors for rheumatoid arthritis. (C) 1997 Elsevier Science Ltd.