Kang, Dongwei; Feng, Da; Sun, Yanying; Fang, Zengjun; Wei, Fenju; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published the artcile< Structure-Based Bioisosterism Yields HIV-1 NNRTIs with Improved Drug-Resistance Profiles and Favorable Pharmacokinetic Properties>, Related Products of 18740-39-1, the main research area is thiophenepyrimidine piperidine substituted preparation antiHIV activity.
The development of efficacious NNRTIs for AIDS therapy commonly encountered the rapid generation of drug-resistant mutations, which becomes a major impediment to effective anti-HIV treatment. Using a structure-based bioisosterism strategy, a series of piperidine-substituted thiophene[2,3-d]pyrimidine derivatives were designed and synthesized. Compound I yielded the greatest potency, exhibiting significantly better anti-HIV-1 activity than ETR against all of the tested NNRTI-resistant HIV-1 strains. In addition, the phenotypic (cross)resistance of I and other NRTIs to the different selected HIV-1 strains was evaluated. As expected, no phenotypic cross-resistance against the NRTIs (AZT and PMPA) was observed with the mutant Ires strain. Furthermore, I was identified with improved solubility, lower CYP liability, and hERG inhibition. Remarkably, I exhibited optimal pharmacokinetic properties in rats (F = 37.06%) and safety in mice (LD50 > 2000 mg/kg), which highlights I as a promising anti-HIV-1 drug candidate.
Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Related Products of 18740-39-1.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia