Verubulin

4‐Aminoquinazolines are an important class of heterocyclic aromatic compounds with extensive applications in pharmaceutical synthesis and materials science. Herein, we present a rapid, cost‐effective, and efficient approach for N‐(alkyl)arylation of 4‐chloroquinazolines using PEG‐400 as a green solvent alternative in both microwave and conventional heating reactors. These methodologies demonstrate broad compatibility with various substituted amines, yielding favorable outcomes. The developed approach enabled the synthesis of Verubulin, a promising antineoplastic agent for treating several types of cancer, alongside a novel drug analogue, highlighting its potential utility in sustainable drug synthesis and discovery.

Drug-induced cardiotoxicity represents one of the most common causes of attrition of drug candidates in preclinical and clinical development. For this reason, the evaluation of cardiac toxicity is essential during drug development and regulatory review. In the present study, drug-induced postmarket adverse event combinations from the FDA Adverse Event Reporting System were extracted for 2002 drugs using 243 cardiac toxicity-related preferred terms (PTs). These PTs were combined into 12 groups based on their clinical relevance to serve as training sets. The optimal classification scheme was determined using a combination of data sources that included drug labeling information, published literature, clinical study data, and postmarket surveillance data. Two commercial QSAR platforms were used to construct 12 models, including general cardiac toxicity, cardiac ischemia, heart failure, cardiac valve disease, myocardial disease, pericardial disease, structural heart disease, cardiac arrhythmia, Torsades de Pointes, long QT syndrome, atrial fibrillation and ventricular arrhythmia, and cardiac arrest. The cross-validated performance for the new models reached a sensitivity of up to 80% and negative predictivity of up to 80%. These new models covering a wide range of cardiac endpoints will provide fast, reliable, and comprehensive predictions of potential cardiotoxic compounds in drug discovery and regulatory safety assessment.