OPC-15161 | 121071-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: OPC-15161
• 英文别名: 2(1H)-Pyrazinone, 6-(1H-indol-3-ylmethyl)-5-methoxy-3-(2-methylpropyl)-, 4-oxide；6-(1H-indol-3-ylmethyl)-5-methoxy-3-(2-methylpropyl)-4-oxido-1H-pyrazin-4-ium-2-one
• CAS: 121071-92-9
• 化学式: C₁₈H₂₁N₃O₃
• 分子量: 327.383
• InChiKey: AFTLYEDBVFGRNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  OPC-15161 生成 3-Acetoxy-5-(indol-3-yl)methyl-2-isobutyl-6-methoxypyrazine 1-oxide
  参考文献：
  名称：

  Indole derivatives

  摘要：

  通用公式（1）表示的新的吲哚衍生物及其盐具有抑制豚鼠巨噬细胞释放的超氧化物（O.sub.2.sup.-）的作用，例如，对马杉肾炎引起的抗白蛋白尿活性，并且在各种临床领域中作为预防和治疗与上述超氧自由基相关的疾病和情况的药物，例如自身免疫疾病（例如风湿病），动脉硬化，缺血性疾病，缺血性脑病，肝功能不全和肾功能不全，以及作为预防和治疗肾炎的药物。

  公开号：

  US05238938A1
• 作为产物：
  描述：

  以 乙醇 、 水 为溶剂， 以91.2%的产率得到OPC-15161
  参考文献：
  名称：

  Tone, Hitoshi; Matoba, Katsuhide; Goto, Fumitaka, Organic Process Research and Development, 2000, vol. 4, # 5, p. 312 - 317

  摘要：

  DOI：

文献信息

• A Novel Thiolate Mediated Cyclization to OPC-15161
  作者：Koichi Shinhama、Katsuhide Matoba、Yasuhiro Torisawa、Jun-ichi Minamikawa

  DOI：10.1016/s0040-4020(00)00670-0

  日期：2000.9

  developed via novel pyrazine ring closure promoted by a lithium thiolate anion. The key intermediate (4) was prepared in a one-pot procedure by treating the methyl ester (2) with a lithium arylthiolate. This protocol does not require a free acid intermediate and thus can establish the shortest route to pyrazine dioxide skeleton from tryptophan ester derivatives. In the present transformation, lithium arylthiolates

  通过硫醇锂阴离子促进的新型吡嗪环闭合，开发了一种有效的合成OPC-15161（1）的途径。通过处理甲酯（2），通过一锅法制备关键中间体（4）。）和芳基硫醇锂。该方案不需要游离酸中间体，因此可以建立从色氨酸酯衍生物到二嗪嗪骨架的最短途径。在目前的转化中，芳基硫醇锂可以表现出芳基硫醇铝的作用，而不像烷基硫醇锂那样经常将酯裂解成相应的酸。一锅式反应在单个烧瓶中涉及冗长的多个步骤，在当代有机合成中非常重要。利用能促进几种转化的催化或化学计量的启动子是这种反应成功的关键。在本文中，我们想披露在我们的过程研究中发现的有趣的一锅法转化，它为我们提供了有关金属硫醇盐反应性的新颖信息。
• INDOLE DERIVATIVES, PREPARATION THEREOF, AND DRUG FOR PREVENTING AND TREATING NEPHRITIS CONTAINING SAME
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP0411150A1

  公开（公告）日：1991-02-06

  This invention relates to indole derivatives of general formula (1) and salts thereof, a method for preparing same, and applications thereof in the prevention and treatment of nephritis, wherein R represents hydrogen, cyano or one of various other substituents, 1 is an integer of 1 or 2, R' represents hydrogen, one of various substituents or a group of formula (2) (wherein A represents a single bond, -CH(OH)-, -CH=, -C(=0)- or alkyl, and R2, R3, R4, R5 and R6 each represents one of various substituents),and Z represents hydrogen or a group of formula (2) provided that R1 represents a group of formula (2) when Z represents hydrogen.

  本发明涉及通式(1)的吲哚衍生物及其盐、制备方法以及在预防和治疗肾炎中的应用，其中R代表氢、氰基或其它各种取代基之一，1为1或2的整数，R'代表氢、其中 A 代表单键、-CH(OH)-、-CH=、-C(=0)- 或烷基，R2、R3、R4、R5 和 R6 各代表各种取代基之一），Z 代表氢或式（2）基团，但当 Z 代表氢时，R1 代表式（2）基团。
• Kita, Yasuyuki; Akai, Shuji; Fujioka, Hiromichi, Journal of the Chemical Society. Perkin transactions I, 1994, # 7, p. 875 - 884
  作者：Kita, Yasuyuki、Akai, Shuji、Fujioka, Hiromichi、Tamura, Yasumitsu、Tone, Hitoshi、Taniguchi, Youichi

  DOI：——

  日期：——
• The first total synthesis of OPC-15161
  作者：Yoshihiko Ito、Hideaki Sato、Masahiro Murakami

  DOI：10.1021/jo00016a012

  日期：1991.8

  The first total synthesis of OPC-15161, a novel inhibitor of superoxide generation by guinea pig macrophages, has been accomplished via a convergent and efficient route exploiting the coupling of the fully functionalized pyrazine part with the indolyl group. 2-(Hydroxyimino)-4-methylpentanoic acid and ethyl aminocyanoacetate were condensed with DCC to afford the amide 3, which was converted to pyrazinone N-oxide 4 via intramolecular cyclization between the oxime and cyano groups. O-Benzylation of 4 followed by reduction of the ethoxycarbonyl group by DIBALH gave the aminopyrazine alcohol 7. The aryl chloride 8 was obtained by the direct substitutive deamination using isoamyl nitrite and copper salts. After protection of the hydroxyl group, the methoxy group was introduced at the 5-position via treatment of 2,5-bis(benzyloxy)pyrazine 4-oxide 10 with methoxide to afford 11. The methoxy compound 11 was converted to benzylic iodide 14 via deprotection, mesylation, and iodination. The functionalized pyrazine skeleton 14 was coupled with the zinc salt of indole to produce 17, which upon catalytic hydrogenolysis afforded OPC-15161.
• Total synthesis of a new inhibitor of superoxide anion generation, opc-15161
  作者：Yasuyuki Kita、Shuji Akai、Hiromichi Fujioka、Yasumitsu Tamura、Hitoshi Tone、Youichi Taniguchi

  DOI：10.1016/s0040-4039(00)79453-6

  日期：1991.10

  The first total synthesis of a new inhibitor of superoxide anion generation, OPC-15161, was achieved from tryptophan methyl ester in 4-6 steps in 9.9-10.6% overall yields.