1268381-89-0Relevant 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 (2017/02/15)
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.
6-cyclohexylpyrimidone HIV reverse transcriptase inhibitor, preparation method and application thereof
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Paragraph 0023; 0024, (2017/07/20)
The invention belongs to the technical field of drugs, and particularly discloses 5-isopropyl-2-(4-hydrocarbyl methanoyl phenyl carbonyl methylsulfonyl)-6-cyclohexylpyrimidone, N-oxide shown as the formula I, a three-dimensional isomer form, a three-dimen
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
scheme or table, 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.
