N-α-Boc-N-phenethylglycine benzyl ester | 172834-24-1

• 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-α-Boc-N-phenethylglycine benzyl ester
• 英文别名: Benzyl 2-[(2-methylpropan-2-yl)oxycarbonyl-(2-phenylethyl)amino]acetate
• CAS: 172834-24-1
• 化学式: C₂₂H₂₇NO₄
• 分子量: 369.461
• InChiKey: GHHMBRSMIPFOLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-α-Boc-N-phenethylglycine benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 N-(tert-butoxycarbonyl)-N-phenethylglycine
  参考文献：
  名称：

  Bradykinin Receptor Antagonists Containing N-Substituted Amino Acids:  In Vitro and in Vivo B₂ and B₁ Receptor Antagonist Activity

  摘要：

  We report a systematic probing of the structural requirements of the bradykinin (BK) type 2 (B-2) receptor for antagonist activity by incorporating N-Alkyl-amino acid residues at positions 7 and 8 of a potent antagonist sequence. Compound 1 (D-Arg(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-Thi(5)-Ser(6)- D-Tic(7)-N-Chg(8)-Arg(9), CP-0597)(1,2) is a potent (pA(2) = 9.3, rat uterus; pK(i) = 9.62, binding, human receptor clone) Bz receptor antagonist devoid of in vitro B-1 antagonist activity (rabbit aorta). Compound 1 exhibits high potency (ED(50) = 29.2 pmol/kg/min, iv, rabbit) and duration of action when tested in models for in vivo B-2 antagonist activity. Although devoid of activity in a classic B-1 isolated tissue assay, B-1 antagonist activity for 1 was demonstrated in vivo, in a LPS-treated, inducible BK1 receptor rabbit blood pressure model (ED(50) = 1.7 nmol/kg/min). D-Arg(0) of 1 can be formally replaced by an achiral arginine surrogate, without significant loss in antagonist potency on rat uterus (compound 11, B-2 pA(2) = 9.1). Antagonist 13 (Hyp(2), NChg(8)), pK(i) = 10.2, and agonist 4 (N-methylcyclohexyl-Gly(8)), pK(i) = 10.1, also exhibited substantial binding to guinea pig ileum membrane receptors as well as a human Bz receptor clone. Very minor structural changes in the N-alkyl amino acid residues in positions 7 and 8 can modify the activity of this class of compounds from being extremely potent antagonists to tight binding partial or full agonists. These studies have resulted in a series of compounds containing inexpensive amino acid residues but which produce broad spectrum BK receptor blocking potency and exceptional in vivo duration of action.

  DOI：

  10.1021/jm950716i
• 作为产物：
  描述：

  2-溴乙酸苄酯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 30.0h， 生成 N-α-Boc-N-phenethylglycine benzyl ester
  参考文献：
  名称：

  Bradykinin Receptor Antagonists Containing N-Substituted Amino Acids:  In Vitro and in Vivo B₂ and B₁ Receptor Antagonist Activity

  摘要：

  We report a systematic probing of the structural requirements of the bradykinin (BK) type 2 (B-2) receptor for antagonist activity by incorporating N-Alkyl-amino acid residues at positions 7 and 8 of a potent antagonist sequence. Compound 1 (D-Arg(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-Thi(5)-Ser(6)- D-Tic(7)-N-Chg(8)-Arg(9), CP-0597)(1,2) is a potent (pA(2) = 9.3, rat uterus; pK(i) = 9.62, binding, human receptor clone) Bz receptor antagonist devoid of in vitro B-1 antagonist activity (rabbit aorta). Compound 1 exhibits high potency (ED(50) = 29.2 pmol/kg/min, iv, rabbit) and duration of action when tested in models for in vivo B-2 antagonist activity. Although devoid of activity in a classic B-1 isolated tissue assay, B-1 antagonist activity for 1 was demonstrated in vivo, in a LPS-treated, inducible BK1 receptor rabbit blood pressure model (ED(50) = 1.7 nmol/kg/min). D-Arg(0) of 1 can be formally replaced by an achiral arginine surrogate, without significant loss in antagonist potency on rat uterus (compound 11, B-2 pA(2) = 9.1). Antagonist 13 (Hyp(2), NChg(8)), pK(i) = 10.2, and agonist 4 (N-methylcyclohexyl-Gly(8)), pK(i) = 10.1, also exhibited substantial binding to guinea pig ileum membrane receptors as well as a human Bz receptor clone. Very minor structural changes in the N-alkyl amino acid residues in positions 7 and 8 can modify the activity of this class of compounds from being extremely potent antagonists to tight binding partial or full agonists. These studies have resulted in a series of compounds containing inexpensive amino acid residues but which produce broad spectrum BK receptor blocking potency and exceptional in vivo duration of action.

  DOI：

  10.1021/jm950716i

文献信息

• Bradykinin antagonist peptides incorporating N-substituted glycines
  申请人：Cortech, Inc.

  公开号：US05700779A1

  公开（公告）日：1997-12-23

  The present invention provides bradykinin type peptides containing N-substituted glycines, particularly bradykinin antagonist peptides useful for the treatment of conditions mediated by bradykinin including pain and inflammation.

  本发明提供了含有N-取代甘氨酸的激肽类肽段，特别是用于治疗由激肽介导的疾病，包括疼痛和炎症的激肽拮抗肽段。
• BRADYKININ ANTAGONIST PEPTIDES INCORPORATING N-SUBSTITUTED GLYCINES
  申请人：CORTECH, INC.

  公开号：EP0813544B1

  公开（公告）日：2004-10-27
• EP0813544A4
  申请人：——

  公开号：EP0813544A4

  公开（公告）日：1998-01-07
• US5700779A
  申请人：——

  公开号：US5700779A

  公开（公告）日：1997-12-23
• [EN] BRADYKININ ANTAGONIST PEPTIDES INCORPORATING N-SUBSTITUTED GLYCINES<br/>[FR] PEPTIDES ANTAGONISTES DE LA BRADYKININE CONTENANT DES GLYCINES SUBSTITUEES EN N
  申请人：CORTECH, INC.

  公开号：WO1995024422A1

  公开（公告）日：1995-09-14

  (EN) The present invention provides bradykinin type peptides containing N-substituted glycines, particularly bradykinin antagonist peptides useful for the treatment of conditions mediated by bradykinin including pain and inflammation.(FR) L'invention concerne des peptides du type bradykinine contenant des glycines substituées en N, et plus particulièrement des peptides antagonistes de la bradykinine utiles pour le traitement de pathologies induites par la bradykinine, dont la douleur et l'inflammation.