6-bromo-2-<oxy>naphthalene | 174537-82-7

• 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: 6-bromo-2-<oxy>naphthalene
• 英文别名: Ditert-butyl 2-(6-bromonaphthalen-2-yl)oxypropanedioate
• CAS: 174537-82-7
• 化学式: C₂₁H₂₅BrO₅
• 分子量: 437.331
• InChiKey: OQDAPIOOJCRWTA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-bromo-2-<oxy>naphthalene 在 sodium hexamethyldisilazane 、 N-氟代双苯磺酰胺 作用下， 生成 6-bromo-2-<oxy>naphthalene
  参考文献：
  名称：

  4‘-O-[2-(2-Fluoromalonyl)]-l-tyrosine:  A Phosphotyrosyl Mimic for the Preparation of Signal Transduction Inhibitory Peptides

  摘要：

  Development of phosphotyrosyl (pTyr) mimetics which are stable to protein-tyrosine phosphatases (PTPs), yet can retain biological potency when incorporated into peptides, is an active area of drug development. Since a majority of pTyr mimetics derive their ''phosphofunctionality'' from phosphorus-containing moieties, such as phosphonates, evolution of new inhibitors and modes of prodrug derivatization have been restricted to chemistries appropriate for phosphorus-containing moieties. A new, nonphosphorus-containing pTyr mimetic has recently been reported, L-O-(2-malonyl)tyrosine (OMT, 5), which can be incorporated into peptides that exhibit good PTP and Src homology 2 (SH2) domain inhibitory potency. For phosphonate-based pTyr mimetics such as phosphonomethyl phenylalanine (Pmp, 2), introduction of fluorines a to the phosphorus has provided higher affinity pTyr mimetics. This strategy has now been applied to OR IT, and herein is reported 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine (FOMT) 6), a new fluorine-containing nonphosphorus pTyr mimetic. Incorporation of FOMT into appropriate peptides results in good inhibition of both PTP and SH2 domains. In an assay measuring the inhibition of PTP 1B-mediated dephosphorylation of phosphorylated insulin receptor, the peptide Ac-DA-D-E-X-L-amide exhibited a 10-fold enhancement in inhibitory potency for X = FOMT (19) (IC50 = 1 mu M) relative to the unfluorinated peptide, X = OMT (18) (IC50 = 10 mu M). Molecular modeling indicated that this increased affinity may be attributable to new hydrogen-bonding interactions between the fluorine and the enzyme catalytic site, and not due to lowering of pK(a) values. In a competition binding assay using the p85 PI 3-kinase C-terminal SH2 domain GST fusion construct, the inhibitory peptide, Ac-D-X-V-P-M-L-amide, showed no enhancement of inhibitory potency for X = FOMT (22) (IC50 = 18 mu M) relative to the unfluorinated peptide, X = OMT (21) (IC50 = 14 mu M). The use of FOMT would therefore appear to have particular potential for the development of PTP inhibitors.

  DOI：

  10.1021/jm950621g
• 作为产物：
  描述：

  6-溴-2-萘酚 、 2-偶氮基-1,3-二[(2-甲基丙烷-2-基)氧基]-3-氧代丙-1-烯-1-醇 在 dirhodium tetraacetate 作用下， 以 苯 为溶剂， 以20%的产率得到6-bromo-2-<oxy>naphthalene
  参考文献：
  名称：

  4‘-O-[2-(2-Fluoromalonyl)]-l-tyrosine:  A Phosphotyrosyl Mimic for the Preparation of Signal Transduction Inhibitory Peptides

  摘要：

  Development of phosphotyrosyl (pTyr) mimetics which are stable to protein-tyrosine phosphatases (PTPs), yet can retain biological potency when incorporated into peptides, is an active area of drug development. Since a majority of pTyr mimetics derive their ''phosphofunctionality'' from phosphorus-containing moieties, such as phosphonates, evolution of new inhibitors and modes of prodrug derivatization have been restricted to chemistries appropriate for phosphorus-containing moieties. A new, nonphosphorus-containing pTyr mimetic has recently been reported, L-O-(2-malonyl)tyrosine (OMT, 5), which can be incorporated into peptides that exhibit good PTP and Src homology 2 (SH2) domain inhibitory potency. For phosphonate-based pTyr mimetics such as phosphonomethyl phenylalanine (Pmp, 2), introduction of fluorines a to the phosphorus has provided higher affinity pTyr mimetics. This strategy has now been applied to OR IT, and herein is reported 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine (FOMT) 6), a new fluorine-containing nonphosphorus pTyr mimetic. Incorporation of FOMT into appropriate peptides results in good inhibition of both PTP and SH2 domains. In an assay measuring the inhibition of PTP 1B-mediated dephosphorylation of phosphorylated insulin receptor, the peptide Ac-DA-D-E-X-L-amide exhibited a 10-fold enhancement in inhibitory potency for X = FOMT (19) (IC50 = 1 mu M) relative to the unfluorinated peptide, X = OMT (18) (IC50 = 10 mu M). Molecular modeling indicated that this increased affinity may be attributable to new hydrogen-bonding interactions between the fluorine and the enzyme catalytic site, and not due to lowering of pK(a) values. In a competition binding assay using the p85 PI 3-kinase C-terminal SH2 domain GST fusion construct, the inhibitory peptide, Ac-D-X-V-P-M-L-amide, showed no enhancement of inhibitory potency for X = FOMT (22) (IC50 = 18 mu M) relative to the unfluorinated peptide, X = OMT (21) (IC50 = 14 mu M). The use of FOMT would therefore appear to have particular potential for the development of PTP inhibitors.

  DOI：

  10.1021/jm950621g

文献信息

• 4‘-<i>O</i>-[2-(2-Fluoromalonyl)]-<scp>l</scp>-tyrosine:  A Phosphotyrosyl Mimic for the Preparation of Signal Transduction Inhibitory Peptides
  作者：Terrence R. Burke,、Bin Ye、Miki Akamatsu、Harry Ford,、Xinjian Yan、Hemanta K. Kole、Gert Wolf、Steven E. Shoelson、Peter P. Roller

  DOI：10.1021/jm950621g

  日期：1996.1.1

  Development of phosphotyrosyl (pTyr) mimetics which are stable to protein-tyrosine phosphatases (PTPs), yet can retain biological potency when incorporated into peptides, is an active area of drug development. Since a majority of pTyr mimetics derive their ''phosphofunctionality'' from phosphorus-containing moieties, such as phosphonates, evolution of new inhibitors and modes of prodrug derivatization have been restricted to chemistries appropriate for phosphorus-containing moieties. A new, nonphosphorus-containing pTyr mimetic has recently been reported, L-O-(2-malonyl)tyrosine (OMT, 5), which can be incorporated into peptides that exhibit good PTP and Src homology 2 (SH2) domain inhibitory potency. For phosphonate-based pTyr mimetics such as phosphonomethyl phenylalanine (Pmp, 2), introduction of fluorines a to the phosphorus has provided higher affinity pTyr mimetics. This strategy has now been applied to OR IT, and herein is reported 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine (FOMT) 6), a new fluorine-containing nonphosphorus pTyr mimetic. Incorporation of FOMT into appropriate peptides results in good inhibition of both PTP and SH2 domains. In an assay measuring the inhibition of PTP 1B-mediated dephosphorylation of phosphorylated insulin receptor, the peptide Ac-DA-D-E-X-L-amide exhibited a 10-fold enhancement in inhibitory potency for X = FOMT (19) (IC50 = 1 mu M) relative to the unfluorinated peptide, X = OMT (18) (IC50 = 10 mu M). Molecular modeling indicated that this increased affinity may be attributable to new hydrogen-bonding interactions between the fluorine and the enzyme catalytic site, and not due to lowering of pK(a) values. In a competition binding assay using the p85 PI 3-kinase C-terminal SH2 domain GST fusion construct, the inhibitory peptide, Ac-D-X-V-P-M-L-amide, showed no enhancement of inhibitory potency for X = FOMT (22) (IC50 = 18 mu M) relative to the unfluorinated peptide, X = OMT (21) (IC50 = 14 mu M). The use of FOMT would therefore appear to have particular potential for the development of PTP inhibitors.