Tantak Mukund P, Rayala Ramanjaneyulu, Chaudhari Prakash, Danta Chhanda C, Nefzi Adel
Herbert Wertheim College of Medicine, Center for Translational Science, Florida International University, Port Saint Lucie, FL 34987, USA.
Department of Chemistry and Biochemistry, College of Arts, Sciences & Education, Florida International University, Miami, FL 33199, USA.
Pharmaceuticals (Basel). 2024 Nov 22;17(12):1566. doi: 10.3390/ph17121566.
Small-molecule probes are powerful tools for studying biological systems and can serve as lead compounds for developing new therapeutics. Especially, nitrogen heterocycles are of considerable importance in the pharmaceutical field. These compounds are found in numerous bioactive structures. Their synthesis often requires several steps or the use of functionalized starting materials. This review describes the use of vicinal diamines generated from modified short peptides to access substituted diaza- and triazacyclic compounds. Small-molecule diaza- and triazacyclic compounds with different substitution patterns and embedded in various molecular frameworks constitute important structure classes in the search for bioactivity. The compounds are designed to follow known drug likeness rules, including "Lipinski's Rule of Five". The screening of diazacyclic and traizacyclic libraries has shown the utility of these classes of compounds for the de novo identification of highly active compounds, including antimalarials, antimicrobial compounds, antifibrotic compounds, potent analgesics, and antitumor agents. Examples of the synthesis of diazacyclic and triazacyclic small-molecule libraries from vicinal chiral polyamines generated from modified short peptides and their application for the identification of highly active compounds are described.
小分子探针是研究生物系统的有力工具，可作为开发新疗法的先导化合物。特别是，氮杂环在制药领域具有相当重要的意义。这些化合物存在于众多生物活性结构中。它们的合成通常需要多个步骤或使用官能化的起始原料。本综述描述了利用修饰短肽生成的邻二胺来制备取代的二氮杂环和三氮杂环化合物。具有不同取代模式并嵌入各种分子框架中的小分子二氮杂环和三氮杂环化合物是寻找生物活性过程中的重要结构类别。这些化合物的设计遵循已知的类药规则，包括“Lipinski五规则”。对二氮杂环和三氮杂环文库的筛选表明，这些类别的化合物可用于从头鉴定高活性化合物，包括抗疟药、抗菌化合物、抗纤维化化合物、强效镇痛药和抗肿瘤剂。本文描述了由修饰短肽生成的邻位手性多胺合成二氮杂环和三氮杂环小分子文库的实例及其在鉴定高活性化合物中的应用。
