α-N-(tert-butoxycarbonyl)-δ-<(N¹-(tert-butoxycarbonyl)-S-methyl)-1-isothioureido>-L-norvaline tert-butyl ester | 133565-51-2

• 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: α-N-(tert-butoxycarbonyl)-δ-<(N¹-(tert-butoxycarbonyl)-S-methyl)-1-isothioureido>-L-norvaline tert-butyl ester
• 英文别名: α-N-t-butoxycarbonyl-δ-<(N-t-butoxycarbonyl-S-methyl)isothioureido>-L-norvaline-t-butyl ester；tert-butyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-[[[(2-methylpropan-2-yl)oxycarbonylamino]-methylsulfanylmethylidene]amino]pentanoate
• CAS: 133565-51-2
• 化学式: C₂₁H₃₉N₃O₆S
• 分子量: 461.623
• InChiKey: ULNYRCOCBBXBEM-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  α-N-(tert-butoxycarbonyl)-δ-<(N¹-(tert-butoxycarbonyl)-S-methyl)-1-isothioureido>-L-norvaline tert-butyl ester 在 palladium on activated charcoal 盐酸 、 氢气 、 silver nitrate 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 23.0 ℃ 、101.33 kPa 条件下， 反应 35.0h， 生成 L-N^G-hydroxy-N^G-methylarginine bistrifluoroacetate salt
  参考文献：
  名称：

  Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation

  摘要：

  L-N(G)-Methylarginine (NMA) is an established mechanism-based inactivator of murine macrophage nitric oxide synthase (mNOS). In this report, NMA is shown to irreversibly inhibit both mNOS (k(inact)=0.08 min-1) and there combinant constitutive brain NOS (bNOS). For both NOS isoforms, metabolism of NMA parallels that of the natural substrate L-arginine (ARG), in that it undergoes a regiospecific, NADPH-dependent hydroxylation to form L-N(G)-hydroxy-N(G)-methylarginine (NOHNMA). This intermediate then undergoes further NADPH-dependent oxidation to form L-citrulline (CIT). Authentic NOHNMA, synthesized from L-ornithine, irreversibly inhibited both mNOS(k(inact)=0.10 min-1)and bNOS in an NADPH-dependent reaction. The conversion of either NMA or NOHNMA to CIT correlated with irreversible enzyme inactivation. Thus, the data suggest that enzyme inhibition occurs as a consequence of oxidative metabolism of the intermediate, NOHNMA. A unified mechanism is proposed that accounts for NO biosynthesis from ARG, for the inactivation of NOS by NMA and for the intermediacy of hydroxylated ARG or NMA derivatives in these processes.

  DOI：

  10.1021/jm00056a009
• 作为产物：
  描述：

  tert-butyl (2S)-5-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate 在 氨 、 碳酸氢钠 、 calcium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 水 、 乙腈 为溶剂， 反应 33.0h， 生成 α-N-(tert-butoxycarbonyl)-δ-<(N¹-(tert-butoxycarbonyl)-S-methyl)-1-isothioureido>-L-norvaline tert-butyl ester
  参考文献：
  名称：

  Synthesis of the putative l-arginine metabolite L-NG-hydroxyarginine

  摘要：

  Syntheses of L-N(G)-hydroxyarginine (1), the putative biosynthetic precursor of nitric oxide, and the N-15 labelled analogs 9 and 10 using L-ornithine as the enantiopure starting material is reported.

  DOI：

  10.1016/s0040-4039(00)92109-9

文献信息

• Guanidine-substituted imidazoles as inhibitors of nitric oxide synthase
  作者：Robert N. Atkinson、S. Bruce King

  DOI：10.1016/s0960-894x(99)00509-0

  日期：1999.10

  Guanidine-substituted imidazoles were prepared and evaluated as inhibitors of the three isoforms of nitric oxide synthase. These results identify a new 2-substituted imidazole as an isoform selective inhibitor and illustrate the possible importance of the L-arginine side chain in selective isoform recognition. (C) 1999 Elsevier Science Ltd. All rights reserved.