Boc-Leu-Gly(tBu)-NHMe | 178932-88-2

• 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: Boc-Leu-Gly(tBu)-NHMe
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 178932-88-2
• 化学式: C₁₈H₃₅N₃O₄
• 分子量: 357.494
• InChiKey: ZIDSUTLHOXMUSY-QWHCGFSZSA-N

物化性质

• 沸点：
  551.8±35.0 °C(Predicted)
• 密度：
  1.018±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  96.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Boc-Leu-Gly(tBu)-NHMe 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以0.054 g的产率得到L-亮氨酰-N,3-二甲基-L-缬氨酰胺
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 N-羟基丁二酰亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.67h， 生成 Boc-Leu-Gly(tBu)-NHMe
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848

文献信息

• PEPTIDYL COMPOUNDS AND THEIR THERAPEUTIC USE AS INHIBITORS OF METALLOPROTEASES
  申请人：Darwin Discovery Limited

  公开号：EP0784629B1

  公开（公告）日：1999-04-28
• US5994312A
  申请人：——

  公开号：US5994312A

  公开（公告）日：1999-11-30
• US6180611B1
  申请人：——

  公开号：US6180611B1

  公开（公告）日：2001-01-30
• Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1
  作者：M. Burak Onaran、Anthony B. Comeau、Christopher T. Seto

  DOI：10.1021/jo0517848

  日期：2005.12.1

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.