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《Bioorganic & medicinal chemistry》2014,22(12):3220-3226
A series of new diarylpyrimidines (DAPYs) characterized by a halogen atom on the methylene linker between wing I and the central pyrimidine ring was synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. The two most promising compounds 7f and 7g showed excellent activity against wild-type HIV-1 with low nanomolar EC50 values of 0.005 and 0.009 μM, respectively, which were comparable to or more potent than all the reference drugs zidovudine (AZT), lamivudine (3TC), nevirapine (NEV), efavirenz (EFV), delaviridine (DLV) and etravirine (ETV). In particular, 7g also displayed strong activity against the double mutant strain 103N + 181C with an EC50 value of 8.2 μM. The preliminary structure–activity relationship (SAR) and molecular docking analysis of this new series of CHX-DAPYs were also investigated. 相似文献
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Zhan P Liu X Cao Y Wang Y Pannecouque C De Clercq E 《Bioorganic & medicinal chemistry letters》2008,18(20):5368-5371
A novel series of 1,2,3-thiadiazole thioacetanilide (TTA) derivatives have been designed, synthesized and evaluated for its anti-HIV activities in MT-4 cells. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Among them, 2-[4-(2,4-dichlorophenyl)-1,2,3-thiadiazol-5-ylthio]-N-(2-nitrophenyl)acetamide 7d2 was identified as the most promising compound (EC(50)=0.059+/-0.02 microM, CC(50)>283.25 microM, SI>4883). The structure-activity relationship (SAR) of these novel structural congeners is discussed. 相似文献
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Hua Qin Chang Liu Ying Guo Ruiping Wang Jianfang Zhang Liying Ma Zhili Zhang Xiaowei Wang Yuxin Cui Junyi Liu 《Bioorganic & medicinal chemistry》2010,18(9):3231-3237
A series of novel S-DABO analogues (4a1–5a12) have been synthesized by an efficient method and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). The biological testing results clearly indicated that the substitution of halogen at the C5 position of pyrimidine ring could increase the anti-HIV-1 RT activity. The most active compounds showed activity in the low micromole range with IC50 values (IC50 0.18–3.03 μM) comparable to nevirapine (IC50 4.12 μM). The docking showed that a new halogen bond was formed between halogen and carbonyl of TYR188 in the HIV-I RT. 相似文献
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Hua Qin Chang Liu Jianfang Zhang Ying Guo Siwei Zhang Zhili Zhang Xiaowei Wang Liangren Zhang Junyi Liu 《Bioorganic & medicinal chemistry letters》2010,20(9):3003-3005
Novel 2-aryalkylthio-4-amino-6-benzylpyrimidines (3a–i), which can be considered as S-DABO and TMC-125 analogue hybrid molecules, have been designed and synthesized as inhibitors of HIV-1 RT. The results clearly indicated that the changes at the N3/C4 position of pyrimidine ring could affect the hydrogen bonds strength and number between N3/C4 and the Lys101 residue which are indispensable for anti-HIV-1 RT activity. The biological activity results are also in accordance with the docking study. 相似文献
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Xingtao Tian Bingjie Qin Hong Lu Weihong Lai Shibo Jiang Kuo-Hsiung Lee Chin Ho Chen Lan Xie 《Bioorganic & medicinal chemistry letters》2009,19(18):5482-5485
Two series (4 and 5) of diarylpyridine derivatives were designed, synthesized, and evaluated for anti-HIV-1 activity. The most promising compound, 5e, inhibited HIV-1 IIIB, NL4-3, and RTMDR1 with low nanomolar EC50 values and selectivity indexes of >10,000. The results of this study indicate that diarylpyridine can be used as a novel scaffold to derive a new class of potent NNRTIs, active against both wild-type and drug-resistant HIV-1 strains. 相似文献
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Sun LQ Qin B Huang L Qian K Chen CH Lee KH Xie L 《Bioorganic & medicinal chemistry letters》2012,22(7):2376-2379
The current optimization of 2,4-diarylaniline analogs (DAANs) on the central phenyl ring provided a series of new active DAAN derivatives 9a-9e, indicating an accessible modification approach that could improve anti-HIV potency against wild-type and resistant strains, aqueous solubility, and metabolic stability. A new compound 9e not only exhibited extremely high potency against wild-type virus (EC(50) 0.53 nM) and several resistant viral strains (EC(50) 0.36-3.9 nM), but also showed desirable aqueous solubility and metabolic stability, which were comparable or better than those of the anti-HIV-1 drug TMC278 (2). Thus, new compound 9e might be a potential drug candidate for further development of novel next-generation NNRTIs. 相似文献
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