Feng, Da; Wei, Fenju; Sun, Yanying; Sharma, Prem Prakash; Zhang, Tao; Lin, Hao; Rathi, Brijesh; De Clercq, Erik; Pannecouque, Christophe; Kang, Dongwei; Zhan, Peng; Liu, Xinyong published the artcile< Boronic acid-containing diarylpyrimidine derivatives as novel HIV-1 NNRTIs: Design, synthesis and biological evaluation>, HPLC of Formula: 18740-39-1, the main research area is boronic acid diarylpyrimidine preparation human immunodeficiency virus 1 inhibitor; acid boronic diarylpyrimidine preparation HIV1 nonnucleoside reverse transcriptase inhibitor; mol dynamics simulation boronic acid diarylpyrimidine HIV 1 inhibitor.
Drug resistance remains to be a serious problem with type I human immunodeficiency virus (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs). A series of novel boronic acid-containing diarylpyrimidine (DAPY) derivatives were designed via bioisosterism and scaffold-hopping strategies, taking advantage of the ability of a boronic acid group to form multiple hydrogen bonds. The target compounds were synthesized and evaluated for their anti-HIV activities and cytotoxicity in MT-4 cells. Compound 10j yielded the most potent activity and turned out to be a single-digit nanomolar inhibitor towards the HIV-1 IIIB [wild-type (WT) strain], L100I and K103N strains, with 50% effective concentration (EC50) values of 7.19-9.85 nmol/L. Moreover, 10j inhibited the double-mutant strain RES056 with an EC50 value of 77.9 nmol/L, which was 3.3-more potent than that of EFV (EC50 = 260 nmol/L) and comparable to that of ETR (EC50 = 32.2 nmol/L). 10J acted like classical NNRTIs with high affinity for WT HIV-1 reverse transcriptase (RT) with 50% inhibition concentration (IC50) value of 0.1837μmol/L. Furthermore, mol. dynamics simulation indicated that 10j was proposed as a promising mol. for fighting against HIV-1 infection through inhibiting RT activity. Overall, the results demonstrated that 10j could serve as a lead mol. for further modification to address virus-drug resistance.
Chinese Chemical Letters published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, HPLC of Formula: 18740-39-1.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia