Isoquinoline-enrooted organic small-molecules represent a challenging molecular target in the organic synthesis arsenal attributed to their structural diversity and therapeutic importance. Into the bargain, isoquinolines are significant structural frameworks in modern medicinal chemistry and drug development. Consequently, synthetic organic and medicinal chemists have been intensely interested in efficient synthetic tactics for the sustainable construction of isoquinoline frameworks and their derivatives in enantiopure or racemic forms. This review accentuates an overview of the literature on the modern synthetic approaches exploited in synthesising isoquinolines and their core embedded heterocyclic skeletons from 2021 to 2022. In detail, the methodologies and inspected pharmacological studies for the array of diversely functionalized isoquinolines or their core-embedded heterocyclic/carbocyclic structures involving the introduction of substituents at C-1, C-3, and C-4 carbon and N-2 atom, bond constructions at the C₁–N₂ atom and C₃–N₂ atom, and structural scaffolding within isoquinoline compounds have been reviewed. This intensive study highlights the need for and relevance of relatively unexplored bioisosterism employing isoquinoline-based small-molecules in drug design.

中文翻译：

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多种功能化的异喹啉及其核心嵌入的杂环框架：药物化学的特殊支架

异喹啉有机小分子因其结构多样性和治疗重要性而成为有机合成库中具有挑战性的分子靶标。总而言之，异喹啉是现代药物化学和药物开发中重要的结构框架。因此，合成有机化学家和药物化学家对可持续构建对映体纯或外消旋形式的异喹啉骨架及其衍生物的有效合成策略非常感兴趣。本综述重点概述了 2021 年至 2022 年合成异喹啉及其核心嵌入杂环骨架的现代合成方法的文献。详细而言，一系列不同功能化的异喹啉或其核心嵌入杂环的方法学和检查药理学研究/碳环结构涉及在C-1、C-3和C-4碳和N-2原子处引入取代基、在C ₁ –N ₂原子和C ₃ –N ₂原子处的键结构以及内部的结构支架对异喹啉化合物进行了综述。这项深入的研究强调了在药物设计中使用基于异喹啉的小分子的相对未经探索的生物电子等排作用的必要性和相关性。