ethyl 2-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-oxoisoindoline-1-carboxylate | 1198160-55-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: ethyl 2-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-oxoisoindoline-1-carboxylate
• 英文别名: ethyl 2-[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]-3-oxo-1H-isoindole-1-carboxylate
• CAS: 1198160-55-2
• 化学式: C₁₉H₂₄N₂O₅
• 分子量: 360.41
• InChiKey: MNRBRVPEHMJWIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  483.8±45.0 °C(Predicted)
• 密度：
  1.273±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-oxoisoindoline-1-carboxylate 在 三乙胺 、 fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 tert-butyl 3-(1-oxo-3-{[4-(trifluoromethoxy)benzyl]carbamoyl}-1,3-dihydro-2H-isoindol-2-yl)azetidine-1-carboxylate
  参考文献：
  名称：

  3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na_V1.7 with Efficacy in Rat Pain Models

  摘要：

  The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure activity relationships, and in vitro and in vivo characterization of a novel series of Na(V)1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na(V)1.7 potency, selectivity over Na(V)1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity versus Na(V)1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclinical behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.

  DOI：

  10.1021/jm300623u
• 作为产物：
  描述：

  1-叔丁氧羰基-3-胺基环丁胺 、 diethyl α-bromohomophthalate 在 三乙胺 作用下， 以 乙腈 为溶剂， 以63%的产率得到ethyl 2-(1-(tert-butoxycarbonyl)azetidin-3-yl)-3-oxoisoindoline-1-carboxylate
  参考文献：
  名称：

  [EN] ISOINDOLINE DERIVATIVES COMPRISING PHENYL GROUPS AND THEIR USE IN THE TREATMENT OF PAIN DISORDERS
  [FR] DÉRIVÉS ISOINDOLINE COMPRENANT DES GROUPES PHÉNYLES ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES DE LA DOULEUR

  摘要：

  公式I的化合物被要求，其中R1是氢，C1-3烷基，Ci_3烷氧基，氰基，羟基或卤素基；其中所述Ci^烷基可以选择性地被一个或多个取代基独立地选择自羟基，Ci^烷氧基和氟基；所述Ci^烷氧基可以选择性地被一个或多个氟基取代；m为1或2；R2和R3分别且独立地选择自氢，Ci_4卤代烷基，Ci_4卤代烷氧基，卤素，Ci_4烷氧基，Ci_4烷基和C3_7环烷氧基；其中所述C3. γ环烷氧基可以选择性地被一个或多个氟基取代；且R2和R3不能同时为氢；D为C3_7环烷基或C3_7杂环烷基；其中所述Cs-j环烷基或Cs-γ杂环烷基可以选择性地被一个或多个X*取代；X4为卤素，Ci_3烷基，Ci_3烷基0Ci_3烷基，Ci_3烷氧基，苄基，Ci_4烷基磺酰基，氧代，R4O(C=O)，R5(C=O)，或C5.6杂环烷基；其中所述Ci烷基，Ci烷基0Ci烷基，Ci^烷氧基和Ci^烷基磺酰基可以选择性地被一个或多个氟基取代；R4为Ci_4烷基，Ci_4烷基0Ci_4烷基，C5_6环烷基，或芳基；R5为Ci_4烷基，Ci_4氟烷基或Cs_6杂环烷基；Li为Ci_4烷基或键；L2为Ci_3烷基；除了化合物2-(环己基甲基)-3-氧代-N-[2-(三氟甲基)苄基]异吲哚啉-1-羧酰胺；以及其药学上可接受的盐，或其异构体的盐。本发明的化合物在治疗中如疼痛治疗中是有用的。

  公开号：

  WO2009145721A1