(+/-)-(3S,6R)-N-(4-methoxybenzyl)-1-azabicyclo[2.2.1]hept-4-en-2-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (+/-)-(3S,6R)-N-(4-methoxybenzyl)-1-azabicyclo[2.2.1]hept-4-en-2-one
• 英文别名: 2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]hept-5-en-3-one；(1S,4R)-2-[(4-methoxyphenyl)methyl]-2-azabicyclo[2.2.1]hept-5-en-3-one
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: SPQZMOQUMVESPX-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-(3S,6R)-N-(4-methoxybenzyl)-1-azabicyclo[2.2.1]hept-4-en-2-one 在 ammonium cerium(IV) nitrate 作用下， 以 水 、 乙腈 为溶剂， 反应 2.5h， 以26%的产率得到(1S)-(+)-2-氮杂双环[2.2.1]庚-5-烯-3-酮
  参考文献：
  名称：

  Palmer, Christopher F.; McCague, Raymond, Journal of the Chemical Society. Perkin transactions I, 1995, # 10, p. 1201 - 1204

  摘要：

  DOI：
• 作为产物：
  描述：

  (1S,4R)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptane-3,6-dione 在 正丁基锂 、 potassium tert-butylate 、 碘 、 一水合肼 、 N-氟代双苯磺酰胺 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 苯 为溶剂， 反应 22.5h， 生成 (+/-)-(3S,6R)-N-(4-methoxybenzyl)-1-azabicyclo[2.2.1]hept-4-en-2-one
  参考文献：
  名称：

  Fluorinated Conformationally Restricted γ-Aminobutyric Acid Aminotransferase Inhibitors

  摘要：

  On the basis of the structures of several potent inhibitor molecules for gamma-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molecules followed from a readily synthesized ketone intermediate. Three of the molecules were found to be irreversible inhibitors of GABA-AT with comparable or larger k(inact)/K-I values than that of vigabatrin, a clinically used antiepilepsy drug, and the other three were reversible inhibitors. A possible mechanism for inactivation by one of the inactivators is proposed.

  DOI：

  10.1021/jm0608715

文献信息

• [EN] HORMONE RECEPTOR MODULATORS FOR TREATING METABOLIC MUTAGENIC AND FIBROTIC CONDITIONS AND DISORDERS<br/>[FR] MODULATEURS DU RÉCEPTEUR HORMONAL POUR LE TRAITEMENT D'ÉTATS ET DE TROUBLES MÉTABOLIQUES MUTAGÈNES ET FIBROTIQUES
  申请人：ARDELYX INC

  公开号：WO2019055808A1

  公开（公告）日：2019-03-21

  The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): wherein L1, A, X1, X2, Y1, Y2, Y3, Y4, R1, R2, and R3 are described herein.

  这项发明涉及FXR的激活剂，可用于治疗自身免疫性疾病、肝病、肠道疾病、肾脏疾病、癌症以及FXR发挥作用的其他疾病，其化学式为（I）：其中L1、A、X1、X2、Y1、Y2、Y3、Y4、R1、R2和R3如本文所述。
• Regioselective Hydroarylations and Parallel Kinetic Resolution of Vince Lactam
  作者：Adam S. Kamlet、Cathy Préville、Kathleen A. Farley、David W. Piotrowski

  DOI：10.1002/anie.201304818

  日期：2013.9.27

  Two regioselective and complementary hydroarylation reactions of an unsymmetrical cyclic olefin have been developed. The products can be transformed in one step into constrained γ‐amino acids. Regioselective arylation of Vince lactam is controlled by the choice of phosphine ligand enantiomer and the substituent on the amide nitrogen atom. The method was extended to a general regiodivergent parallel

  已经开发了两个不对称环状烯烃的区域选择性和互补性氢芳基化反应。产品可以一步转化为受约束的γ-氨基酸。文斯内酰胺的区域选择性芳基化通过选择膦配体对映体和酰胺氮原子上的取代基来控制。该方法扩展到外消旋内酰胺的一般区域发散平行动力学拆分。
• Unexpected Retroaldol-Aldol Reaction during <i>O</i>-Alkylation of Hydroxylated Vince Lactam Derivatives
  作者：Christoffer Bengtsson、Alexander Wetzel、Joakim Bergman、Jonas Brånalt

  DOI：10.1021/acs.joc.5b02404

  日期：2016.1.15

  The unexpected retroaldol-aldol reaction during O-alkylation of a beta-hydroxy lactam was found to be highly dependent on the temperature and shows a remarkable solvent effect. In DMF, O-alkylation is faster than retroaldol-aldol rearrangement giving exclusively products with retention of configuration. In THF, O-alkylation is slower than rearrangement, giving selectively products with inversion of stereochemistry. In DMSO, a retroaldol reaction followed by fast intramolecular proton transfer occurs to give the ring-opened aldehyde.
• Synthesis of Rigid Bicycloheterocyclic Scaffolds from Vince's Lactam (Enzymatic Resolution of Vince's Lactam)
  作者：Mukund K. Gurjar、Smritilekha Bera、Rohini R. Joshi、Ramesh A. Joshi

  DOI：10.3987/com-03-9841

  日期：——
• Fluorinated Conformationally Restricted γ-Aminobutyric Acid Aminotransferase Inhibitors
  作者：Hejun Lu、Richard B. Silverman

  DOI：10.1021/jm0608715

  日期：2006.12.1

  On the basis of the structures of several potent inhibitor molecules for gamma-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molecules followed from a readily synthesized ketone intermediate. Three of the molecules were found to be irreversible inhibitors of GABA-AT with comparable or larger k(inact)/K-I values than that of vigabatrin, a clinically used antiepilepsy drug, and the other three were reversible inhibitors. A possible mechanism for inactivation by one of the inactivators is proposed.