Design and Synthesis of Quinoline‐Pyrazine Based Carboxamides: Leukemic Cancer Active Ugi Adducts

Abstract

AbstractThe design and synthesis of new chemical entities (NCEs) with suitable physicochemical properties are playing a key role in medicinal research areas. Hence, we have designed and synthesized the 10 diverse scaffolds by rightly selecting the quinoline and pyrazine to articulate carboxamide derivatives in a single‐step process with maximum conversation in a shorter time through diverse studies of Ugi multi‐component reaction. Molecular docking studies against FMS‐like tyrosine kinase‐3 (FLT3) provided well‐clustered solutions for the binding modes of these molecules and shed light on the key structural features governing the binding affinity. Two carboxamides derivatives with 3,4,5‐trimethoxy, and chloro substituents showed comparable potency in Leukemia cell lines and medium efficacy in Breast and Melanoma cancer. These results suggest that pyrazine and quinoline‐based carboxamides may be prominent as new anti‐cancer agents in chemotherapy. Additionally, in silico analysis was employed to predict the comprehensive physicochemical ADME profile (absorption, distribution, metabolism, and excretion) of the carboxamide derivatives which was proven drug‐like properties.