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Cyclin-dependent kinases (CDKs) are promising targets in chemotherapy. In this study, we report a series of 2-anilinopyrimidine derivatives with CDK inhibitory activity. Twenty-one compounds were synthesized and their CDK inhibitory and cytotoxic activities were evaluated. The representative compounds demonstrate potent antiproliferative activities toward different solid cancer cell lines and provide a promising strategy for the treatment of malignant tumors. Compound 5f was the most potent CDK7 inhibitor ( IC 50 = 0.479 µM), compound 5d was the most potent CDK8 inhibitor ( IC 50 = 0.716 µM), and compound 5b was the most potent CDK9 inhibitor ( IC 50 = 0.059 µM). All the compounds satisfied the Lipinski's rule of five (molecular weight < 500 Da, number of hydrogen bond acceptors <10, and octanol-water partition coefficient and hydrogen bond donor values below 5). Compound 5j is a good candidate for lead optimization because it has a non-hydrogen atom (N) of 23, an acceptable ligand efficiency value of 0.38673, and an acceptable ligand lipophilic efficiency value of 5.5526. The synthesized anilinopyrimidine derivatives have potential as anticancer agents.

Background: Outbreaks of methanol poisoning have been described in the medical literature in different regions around the world. Even though in Saudi Arabia a few outbreaks of methanol poisoning have occurred, they remain undocumented. Herein, we describe several cases of methanol poisoning in Saudi Arabia with the goal of increasing awareness about the dangers of methanol poisoning among healthcare staff., Case Presentation: Nine middle-aged Saudi patients (five men aged 24, 26, 27, 36, and 49 years and four females aged 19, 20, 24, and 25 years) were admitted to our emergency department after alcohol consumption. All patients presented with severe metabolic acidosis and some visual impairment. Treatment was initiated based on the clinical suspicion of methanol intoxication because of laboratory test limitations and time constraints. Patients showed improvement and favorable hospital outcomes after aggressive empirical treatment., Conclusions: Many social and cultural factors influence the lack of reporting of methanol poisoning cases in Saudi Arabia. We believe it is important to document these outbreaks to increase the knowledge among healthcare providers and promote public health awareness. A high index of suspicion and the development of local public health networks to monitor, survey, follow-up, and facilitate data exchange can help healthcare providers recognize and aggressively treat affected individuals. Early empiric and aggressive management can greatly decrease morbidity and mortality despite challenges and limited resources., (© 2022. The Author(s).)