6-methoxycarbonylnaphtho[2,3-d]-1,3-dioxole | 107401-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-methoxycarbonylnaphtho[2,3-d]-1,3-dioxole
• 英文别名: Methyl benzo[f][1,3]benzodioxole-6-carboxylate
• CAS: 107401-99-0
• 化学式: C₁₃H₁₀O₄
• 分子量: 230.22
• InChiKey: GDQZCJNAJITGAB-UHFFFAOYSA-N

物化性质

• 熔点：
  118-120 °C
• 沸点：
  372.7±11.0 °C(Predicted)
• 密度：
  1.333±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methoxycarbonylnaphtho[2,3-d]-1,3-dioxole 在 草酰氯 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N,N-dipropylnaphtho[2,3-d][1,3]dioxole-6-carboxamide
  参考文献：
  名称：

  Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives

  摘要：

  Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates gamma-aminobutyric acid type A receptors (GABA(A)R). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABA(A)R by means of a two-microelectrode voltage-clamp technique. GABA(A)R were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABA(A)R. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABA(A) (maximal GABA-induced chloride current modulation (IGABA-max = 1673% +/- 146%, EC50 = 51.7 +/- 9.5 mu M), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 +/- 1.8 mu M, IGABA-max = 760% +/- 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABA(A)R modulators.

  DOI：

  10.1021/jm5002277
• 作为产物：
  描述：

  methyl 5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 苯 为溶剂， 生成 6-methoxycarbonylnaphtho[2,3-d]-1,3-dioxole
  参考文献：
  名称：

  Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives

  摘要：

  Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates gamma-aminobutyric acid type A receptors (GABA(A)R). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABA(A)R by means of a two-microelectrode voltage-clamp technique. GABA(A)R were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABA(A)R. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABA(A) (maximal GABA-induced chloride current modulation (IGABA-max = 1673% +/- 146%, EC50 = 51.7 +/- 9.5 mu M), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 +/- 1.8 mu M, IGABA-max = 760% +/- 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABA(A)R modulators.

  DOI：

  10.1021/jm5002277

文献信息

• Rapid access to benzo-annelated heterocycles, naphthalenes, and polysubstituted benzenes through a novel benzannulation reaction
  作者：Inga Cikotiene、Rita Buksnaitiene、Rokas Sazinas

  DOI：10.1016/j.tet.2010.11.073

  日期：2011.1

  mercaptoacetate triggered benzannulation reaction is described. The precursors are heterocyclic, aromatic or acyclic compounds bearing a carbonyl group at ortho position to an internal alkyne. The methodology does not require transition-metal catalysts and moreover it is general for the preparation of wide range of benzo-annelated heterocycles, naphthalenes and benzenes.

  描述了新颖，高效，强大的巯基乙酸甲酯触发苯环化反应。前体是在内部炔烃的邻位带有羰基的杂环，芳族或无环化合物。该方法不需要过渡金属催化剂，而且通常用于制备各种苯并-退火的杂环，萘和苯。
• The Synthesis of Highly Functionalized Naphthalene Derivatives
  作者：Simon J. Teague、Gregory P. Roth

  DOI：10.1055/s-1986-31667

  日期：——

  Condensation of the α-lithio derivative of 3-substituted 4,4-dialkoxybutanoates, butanenitriles, and butanamides with methoxy-activated aromatic aldehydes, followed by treatment with refluxing dilute sulfuric acid gives rise to substituted naphthalene products. In this manner, 2,6,7-tri- and 2,3,6,7-tetrasubstituted naphthalenes are synthesized in high yields on a multigrarn scale.

  将 3-取代的 4,4-二烷氧基丁酸酯、丁烯腈和丁酰胺的 δ-硫代衍生物与甲氧基活化的芳香醛缩合，然后用回流的稀硫酸处理，可得到取代的萘产品。通过这种方法，可以在多栅规模上高产率合成 2,6,7 三取代萘和 2,3,6,7 四取代萘。
• TEAGUE, S. J.;ROTH, G. P., SYNTHESIS, BRD, 1986, N 5, 427-429
  作者：TEAGUE, S. J.、ROTH, G. P.

  DOI：——

  日期：——
• Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives
  作者：Angela Schöffmann、Laurin Wimmer、Daria Goldmann、Sophia Khom、Juliane Hintersteiner、Igor Baburin、Thomas Schwarz、Michael Hintersteininger、Peter Pakfeifer、Mouhssin Oufir、Matthias Hamburger、Thomas Erker、Gerhard F. Ecker、Marko D. Mihovilovic、Steffen Hering

  DOI：10.1021/jm5002277

  日期：2014.7.10

  Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates gamma-aminobutyric acid type A receptors (GABA(A)R). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABA(A)R by means of a two-microelectrode voltage-clamp technique. GABA(A)R were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABA(A)R. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABA(A) (maximal GABA-induced chloride current modulation (IGABA-max = 1673% +/- 146%, EC50 = 51.7 +/- 9.5 mu M), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 +/- 1.8 mu M, IGABA-max = 760% +/- 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABA(A)R modulators.