1268381-90-3Relevant academic research and scientific papers
6-Cyclohexylmethyl-3-hydroxypyrimidine-2,4-dione as an inhibitor scaffold of HIV reverase transcriptase: Impacts of the 3-OH on inhibiting RNase H and polymerase
Tang, Jing,Kirby, Karen A.,Huber, Andrew D.,Casey, Mary C.,Ji, Juan,Wilson, Daniel J.,Sarafianos, Stefan G.,Wang, Zhengqiang
, p. 168 - 179 (2017)
3-Hydroxypyrimidine-2,4-dione (HPD) represents a versatile chemical core in the design of inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated RNase H and integrase strand transfer (INST). We report herein the design, synthesis and biological evaluation of an HPD subtype (4) featuring a cyclohexylmethyl group at the C-6 position. Antiviral testing showed that most analogues of 4 inhibited HIV-1 in the low nanomolar to submicromolar range, without cytotoxicity at concentrations up to 100?μM. Biochemically, these analogues dually inhibited both the polymerase (pol) and the RNase H functions of RT, but not INST. Co-crystal structure of 4a with RT revealed a nonnucleoside RT inhibitor (NNRTI) binding mode. Interestingly, chemotype 11, the synthetic precursor of 4 lacking the 3-OH group, did not inhibit RNase H while potently inhibiting pol. By virtue of the potent antiviral activity and biochemical RNase H inhibition, HPD subtype 4 could provide a viable platform for eventually achieving potent and selective RNase H inhibition through further medicinal chemistry.
Synthesis and biological evaluation of novel anti-hepatitis C virus (HCV) agents: 2-hydroxylphenethyl sulfanyl-oxopyrimidines
Wu, Daochun,Feng, Yue,Wang, Hua,Yang, Junfeng,Chen, Xian,Wang, Yueping,Cong Lai, Christopher,Zhang, Yufang,Li, Cong,Xia, Xueshan,He, Yanping
, p. 1388 - 1396 (2017/06/05)
A novel series of dihydro-hydroxyl-phene-thylsulfanyl-ω-cyclohexyl/phenyl-oxopyrimidine derivatives have been synthesized and their in vitro anti-hepatitis C virus activities have been evaluated using Huh 7.5.1 cells. Some of the compounds showed moderate
Synthesis and biological evaluation of novel hydroxylphenethyl-S-DACOs as high active anti-HIV agents
Wu, Dao-Chun,Zhuang, Dao-Ming,Liu, Xiao-Feng,Lu, Li-He,Wang, Hua,Li, Cong,Lai, Christopher Cong,Li, Jing-Yun,He, Yan-Ping
, p. 271 - 276 (2013/06/05)
A novel 5-alky-6-(cyclohexylmethyl)-2-((2-hydroxy-2-phenylethyl)thio)- pyrimidin-4(3H)-one derivatives were synthesized and their ability to inhibit HIV evaluated . The screening results revealed that compounds 2a-g had a favorable property in inhibiting
Synthesis and biological evaluation of novel dihydro-aryl/alkylsulfanyl- cyclohexylmethyl-oxopyrimidines (S-DACOs) as high active anti-HIV agents
He, Yan-Ping,Long, Jin,Zhang, Shui-Shuan,Li, Cong,Lai, Christopher Cong,Zhang, Chun-Sheng,Li, Da-Xiong,Zhang, De-Hua,Wang, Hua,Cai, Qing-Qing,Zheng, Yong-Tang
, p. 694 - 697 (2011/03/18)
A novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs) combinatory library was synthesized and evaluated with C8166 cells infected by the HIV-1IIIB in vitro, using Nevirapine (NVP) and Zidovudine (AZT) as positive control.
