Wang, Zhao published the artcileDiscovery of Novel Dihydrothiopyrano[4,3-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs with Significantly Reduced hERG Inhibitory Activity and Improved Resistance Profiles, SDS of cas: 73874-95-0, the main research area is antiHIV antiviral resistance HIV1 infection hERG inhibition.
Enlightened by the available structural biol. information, a novel series of dihydrothiopyrano[4,3-d]pyrimidine derivatives were rationally designed via scaffold hopping and mol. hybridization strategies. Notably, compound 20a yielded exceptionally potent antiviral activities (EC50 = 4.44-54.5 nM) against various HIV-1 strains and improved resistance profiles (RF = 0.5-5.6) compared to etravirine and rilpivirine. Meanwhile, 20a exhibited reduced cytotoxicity (CC50 = 284μM) and higher SI values (SI = 5210-63992). Mol. dynamics simulations were performed to rationalize the distinct resistance profiles. Besides, 20a displayed better solubility (soluble = 12.8μg/mL) and no significant inhibition of the main CYP enzymes. Furthermore, 20a was characterized for prominent metabolic stability and in vivo safety properties. Most importantly, the hERG inhibition profile of 20a (IC50 = 19.84μM) was a remarkable improvement. Overall, 20a possesses huge potential to serve as a promising drug candidate due to its excellent potency, low toxicity, and favorable drug-like properties.
Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, SDS of cas: 73874-95-0.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem