Wang, Zhao; Kang, Dongwei; Feng, Da; Cherukupalli, Srinivasulu; Jiang, Xiangyi; Fu, Zhipeng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published the artcile< Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility>, Formula: C6H2Cl2N2S, the main research area is morpholine diarylpyrimidine synthesis antiHIV NNRTI HIV1 CYP450; HIV-1; Morpholine; NNRTIs; SARs; Tolerant region I; Tolerant region II.
To address the intractable issues of drug resistance and poor solubility, a novel series of morpholine-substituted diarylpyrimidines targeting the tolerant region I and tolerant region II of NNIBP were rationally designed by utilizing the available crystallog. studies. The biol. evaluation results showed that four most promising compounds (14e1, 14g1, 14g2 and 14j2) displayed excellent potency against WT HIV-1 strain with EC50 values ranging from 58 to 87 nM, being far more potent than NVP and comparable to ETV. Besides, some derivatives exhibited moderate activity in inhibiting the mutant HIV-1 strains. More encouragingly, 14d2 (RF = 0.4) possessed higher antiresistance profile than ETV (RF = 6.3) and K-5a2 (RF = 3.0) toward the double mutant strain F227L + V106A. The HIV-1 RT inhibition assay confirmed their binding target. The mol. docking studies were conducted and discussed in detail to rationalize the preliminary SARs. Further test indicated that morpholine could indeed promote the improvement of water solubility Addnl., the in silico prediction of physicochem. properties and CYP enzymic inhibitory ability were investigated to evaluate their drug-like features.
European Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Formula: C6H2Cl2N2S.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia