methyl 7-isocyano-3-phenylthieno[2,3-b]pyrazine-6-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: methyl 7-isocyano-3-phenylthieno[2,3-b]pyrazine-6-carboxylate
• 英文别名: Methyl 7-isocyanato-3-phenylthieno[2,3-b]pyrazine-6-carboxylate
• 化学式: C₁₅H₉N₃O₃S
• 分子量: 311.321
• InChiKey: UORIAVHBEZZUBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3aR,9bR)-2-氨基乙基-6-甲氧基-2,3,3a,4,5,9b-[1H]-六氢苯并[e]异吲哚 、 methyl 7-isocyano-3-phenylthieno[2,3-b]pyrazine-6-carboxylate 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 7-[2-(6-Methoxy-1,3,3a,4,5,9b-hexahydro-benzo[e]isoindol-2-yl)-ethyl]-2-phenyl-5H-9-thia-1,4,5,7-tetraaza-fluorene-6,8-dione
  参考文献：
  名称：

  Structure−Activity Studies for a Novel Series of Tricyclic Substituted Hexahydrobenz[e]isoindole α_1A Adrenoceptor Antagonists as Potential Agents for the Symptomatic Treatment of Benign Prostatic Hyperplasia (BPH)

  摘要：

  In search of a uroselective agent that exhibits a high level of selectivity for the alpha(1A) receptor, a novel series of tricyclic hexahydrobenz[e]isoindoles was synthesized. A generic pharmacophoric model was developed requiring the presence of a basic amine core and a fused heterocyclic side chain separated by an alkyl chain. It was shown that the 6-OMe substitution with R, R stereochemistry of the ring junction of the benz[e]isoindole and a two-carbon spacer chain were optimal. In contrast to the highly specific requirements for the benz[e]isoindole portion and linker chain, a wide variety of tricyclic fused heterocyclic attachments were tolerated with retention of potency and selectivity. In vitro functional assays for the alpha(1) adrenoceptor subtypes were used to further characterize these compounds, and in vivo models of vascular vs prostatic tone were used to assess uroselectivity.

  DOI：

  10.1021/jm990567u
• 作为产物：
  描述：

  2-异亚硝基苯乙酮 在 亚硝酸特丁酯 、 sodium carbonate 、 copper(ll) bromide 、 亚磷酸三乙酯 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 53.0h， 生成 methyl 7-isocyano-3-phenylthieno[2,3-b]pyrazine-6-carboxylate
  参考文献：
  名称：

  Fiduxosin 的可扩展合成

  摘要：

  雅培实验室正在开发 Fiduxosin (1)，用于治疗良性前列腺增生。收敛策略需要以区域特异性方式制备对映体纯的 3,4-顺-二取代吡咯烷和 2,3,5-三取代噻吩并吡嗪的方法。采用对映体纯偶氮甲碱叶立德的 [3+2] 环加成，然后进行非对映体选择性结晶，以制备高非对映体和对映体纯度的苯并吡咯吡咯烷。开发了易于差向异构化的 O-芳基内酯的还原条件，并以高产率完成了醇/苯酚到醚的环化。噻吩并吡嗪是通过缩合巯基乙酸甲酯和区域特异性制备的 2-溴-3-氰基-5-苯基吡嗪来制备的。

  DOI：

  10.1021/op049889k

文献信息

• Structure−Activity Studies for a Novel Series of Tricyclic Substituted Hexahydrobenz[<i>e</i>]isoindole α_1A Adrenoceptor Antagonists as Potential Agents for the Symptomatic Treatment of Benign Prostatic Hyperplasia (BPH)
  作者：Michael D. Meyer、Robert J. Altenbach、Fatima Z. Basha、William A. Carroll、Stephen Condon、Steven W. Elmore、James F. Kerwin、Kevin B. Sippy、Karin Tietje、Michael D. Wendt、Arthur A. Hancock、Michael E. Brune、Steven A. Buckner、Irene Drizin

  DOI：10.1021/jm990567u

  日期：2000.4.1

  In search of a uroselective agent that exhibits a high level of selectivity for the alpha(1A) receptor, a novel series of tricyclic hexahydrobenz[e]isoindoles was synthesized. A generic pharmacophoric model was developed requiring the presence of a basic amine core and a fused heterocyclic side chain separated by an alkyl chain. It was shown that the 6-OMe substitution with R, R stereochemistry of the ring junction of the benz[e]isoindole and a two-carbon spacer chain were optimal. In contrast to the highly specific requirements for the benz[e]isoindole portion and linker chain, a wide variety of tricyclic fused heterocyclic attachments were tolerated with retention of potency and selectivity. In vitro functional assays for the alpha(1) adrenoceptor subtypes were used to further characterize these compounds, and in vivo models of vascular vs prostatic tone were used to assess uroselectivity.
• A Scaleable Synthesis of Fiduxosin
  作者：Anthony R. Haight、Anne E. Bailey、William S. Baker、Michael H. Cain、Richard R. Copp、John A. DeMattei、Kelley L. Ford、Rodger F. Henry、Margaret C. Hsu、Robert F. Keyes、Steven A. King、Maureen A. McLaughlin、Laura M. Melcher、William R. Nadler、Patricia A. Oliver、Shyamal I. Parekh、Hemant H. Patel、Louis S. Seif、Mike A. Staeger、Gregory S. Wayne、Steven J. Wittenberger、Weijiang Zhang

  DOI：10.1021/op049889k

  日期：2004.11.1

  Fiduxosin (1) has been under development at Abbott Laboratories for the treatment of benign prostatic hyperplasia. A convergent strategy required methodologies for preparation of an enantiomerically pure 3,4-cis-disubstituted pyrrolidine and a 2,3,5-trisubstituted thienopyrazine in a regiospecific manner. A [3+2] cycloaddition of an enantiopure azomethine ylide followed by a diastereoselective crystallization

  雅培实验室正在开发 Fiduxosin (1)，用于治疗良性前列腺增生。收敛策略需要以区域特异性方式制备对映体纯的 3,4-顺-二取代吡咯烷和 2,3,5-三取代噻吩并吡嗪的方法。采用对映体纯偶氮甲碱叶立德的 [3+2] 环加成，然后进行非对映体选择性结晶，以制备高非对映体和对映体纯度的苯并吡咯吡咯烷。开发了易于差向异构化的 O-芳基内酯的还原条件，并以高产率完成了醇/苯酚到醚的环化。噻吩并吡嗪是通过缩合巯基乙酸甲酯和区域特异性制备的 2-溴-3-氰基-5-苯基吡嗪来制备的。