(7-chloro-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid | 216678-63-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (7-chloro-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid
• 英文别名: (7-chloro-2(1H)-oxo-1,8-naphthyridin-3-yl)acetic acid；(7-Chloro-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)acetic acid；2-(7-chloro-2-oxo-1H-1,8-naphthyridin-3-yl)acetic acid
• CAS: 216678-63-6
• 化学式: C₁₀H₇ClN₂O₃
• 分子量: 238.63
• InChiKey: SQUHRTZIHAZLKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  79.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (7-chloro-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid 在 lithium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 N-(2-(tert-butyloxycarbonyl)aminoethyl)-N-(7-chloro-2(1H)-oxo-1,8-naphthyridin-3-yl)acetylglycine
  参考文献：
  名称：

  Substituted 1,8-Naphthyridin-2(1H)-ones Are Superior to Thymine in the Recognition of Adenine in Duplex as Well as Triplex Structures

  摘要：

  The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermal stability per modification was dependent on the sequence context, ranging from 2.0 degreesC (in separate positions) to 3.5 degreesC (in adjacent positions) in PNA-DNA duplexes and from 1.2 degreesC (in separate positions) to 3.2 degreesC (in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employed to demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen) recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5 degreesC when incorporated into separated and adjacent positions, respectively. Our results furthermore indicate that the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence of single-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the endstacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crick base pairing within a helix.

  DOI：

  10.1021/ja0117027
• 作为产物：
  描述：

  N-(6-氯-3-甲酰基-2-吡啶)-2,2-二甲基丙酰胺 在 盐酸 、 lithium diisopropyl amide 作用下， 以 1,4-二氧六环 、 乙醚 、 正己烷 为溶剂， 反应 6.83h， 生成 (7-chloro-1,8-naphthyridin-2(1H)-on-3-yl)acetic acid
  参考文献：
  名称：

  Substituted 1,8-Naphthyridin-2(1H)-ones Are Superior to Thymine in the Recognition of Adenine in Duplex as Well as Triplex Structures

  摘要：

  The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermal stability per modification was dependent on the sequence context, ranging from 2.0 degreesC (in separate positions) to 3.5 degreesC (in adjacent positions) in PNA-DNA duplexes and from 1.2 degreesC (in separate positions) to 3.2 degreesC (in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employed to demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen) recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5 degreesC when incorporated into separated and adjacent positions, respectively. Our results furthermore indicate that the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence of single-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the endstacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crick base pairing within a helix.

  DOI：

  10.1021/ja0117027

文献信息

• 1,8-Naphthyridin-2,7-(1,8H)-dione is an effective mimic of protonated cytosine in peptide nucleic acid triplex recognition systems
  作者：Caspar Christensen、Anne B Eldrup、Gerald Haaima、Peter E Nielsen

  DOI：10.1016/s0960-894x(02)00658-3

  日期：2002.11

  A novel bicyclic mimic of protonated cytosine [1,8-naphthyridin-2,7-(1,8H)-dione, (K)] for Hoogsteen type triplex recognition of guanine has been designed for incorporation into peptide nucleic acids. Bis-PNA clamps with the K base incorporated in the Hoogsteen strand showed a significant stabilization of the triplexes at pH 7 as compared to similar triplexes with PNA oligomers containing either cytosine (6.7degreesC per unit) or pseudoisocytosine (1.5degreesC per unit). Cooperative stabilization was observed when the K units were placed in adjacent positions (similar to3degreesC per unit). (C) 2002 Elsevier Science Ltd. All rights reserved.
• PEPTIDE NUCLEIC ACID MONOMERS AND OLIGOMERS
  申请人：NIELSEN, Peter Eigil

  公开号：EP0988045B1

  公开（公告）日：2006-02-08
• US6632919B1
  申请人：——

  公开号：US6632919B1

  公开（公告）日：2003-10-14
• Substituted 1,8-Naphthyridin-2(1<i>H</i>)-ones Are Superior to Thymine in the Recognition of Adenine in Duplex as Well as Triplex Structures
  作者：Anne B. Eldrup、Caspar Christensen、Gerald Haaima、Peter E. Nielsen

  DOI：10.1021/ja0117027

  日期：2002.4.1

  The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermal stability per modification was dependent on the sequence context, ranging from 2.0 degreesC (in separate positions) to 3.5 degreesC (in adjacent positions) in PNA-DNA duplexes and from 1.2 degreesC (in separate positions) to 3.2 degreesC (in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employed to demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen) recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5 degreesC when incorporated into separated and adjacent positions, respectively. Our results furthermore indicate that the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence of single-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the endstacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crick base pairing within a helix.