169772-16-1Relevant academic research and scientific papers
Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase
Sudbeck, Elise A.,Mao, Chen,Vig, Rakesh,Venkatachalam,Tuel-Ahlgren, Lisa,Uckun, Fatih M.
, p. 3225 - 3233 (1998)
Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]- 6-(benzyl)-pyrimidin-4-(1H)-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, 1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 μM.
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
New efficient and flexible synthetic route to Emivirine and its analogs
Li, Li,Ma, Liying,Wang, Xiaowei,Liu, Junyi
, p. 164 - 168 (2013/04/24)
A revised synthetic route to Emivirine (MKC-442) via properly substituted β-keto ester converted from Meldrum's Acid was developed. This method could be applied to the synthesis of a variety of MKC-442 analogues and open the way for their systematic biological evaluation.
Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
Qin, Hua,Liu, Chang,Guo, Ying,Wang, Ruiping,Zhang, Jianfang,Ma, Liying,Zhang, Zhili,Wang, Xiaowei,Cui, Yuxin,Liu, Junyi
scheme or table, p. 3231 - 3237 (2010/07/05)
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.
Synthesis and anti-HIV-1 activity of S-dihydro(alkyloxy)benzyloxypyrimidine derivatives
Rao, Zhi-Kun,Long, Jing,Li, Cong,Zhang, Sui-Shuan,He, Mei,Ou, Ling-Cheng,Zheng, Yong-Tang,He, Yan-Ping
scheme or table, p. 967 - 974 (2009/10/16)
Several 2-heteroaryl-, 2-heteroarylcarbonylmethyl-, 2-arylcarbonylmethyl, and 2-arylethyl derivatives of S-dihydro(alkyloxy)benzyloxypyrimidines have been synthesized and the anti-HIV activities of these compounds were tested in C8166 cell and against RT
Does the 2-methylthiomethyl substituent really confer high anti-HIV-1 activity to S-DABOs?
Sbardella, Gianluca,Mai, Antonello,Artico, Marino,Massa, Silvio,Marceddu, Tiziana,Vargiu, Laura,Marongiu, Maria Elena,La Colla, Paolo
, p. 30 - 39 (2007/10/03)
S-DABO derivatives containing the methylthiomethyl (MTM) group have been synthesized and tested for anti-HIV-1 activity in cell-based assay (MTT and p24 assays) and for their capability to target the HIV-1 reverse transcriptase in enzyme assays. Data of experiments lead to the conclusion that the introduction of a 2-MTM-thio side chain is not sufficient per se to significantly increase S-DABO's potency. Nevertheless, potent MTM-S-DABOs can be obtained by introducing a 2,6-difluorophenylmethyl moiety as a C-6 substituent.
5-alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series
Vig, Rakesh,Mao, Chen,Venkatachalam,Tuel-Ahlgren, Lisa,Sudbeck, Elise A.,Uckun, Fatih M.
, p. 1461 - 1466 (2007/10/03)
Novel dihydroalkoxybenzyloxopyrimidine (S-DABO) derivatives targeting the non-nucleoside inhibitor (NNI) binding site of human immunodeficiency virus (IV) reverse transcriptase (RT) have been synthesized using a novel computer model for the NNI binding pocket and tested for their RT inhibitory activity in cell-free assays using purified recombinant HIV RT as well as for their anti-HIV activity in HTLVIIIB-infected peripheral blood mononuclear cells. Our computational approach allowed the identification of several ligand derivatization sites for the generation of more potent S-DABO derivatives. Our lead S-DABO derivative, 5-isopropyl-2- [(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-one (compound 3), elicited potent anti-HIV activity with an IC50 value of less than 1nM for inhibition of HIV replication without any evidence of cytotoxicity and an unprecedented selectivity index of > 100,000.
Synthesis and Anti-HIV-1 Activity of Thio Analogues of Dihydroalkoxybenzyloxopyrimidines
Mai, Antonello,Artico, Marino,Sbardella, Gianluca,Massa, Silvio,Loi, Anna Giulia,et al.
, p. 3258 - 3263 (2007/10/03)
Various thio analogues of dihydroalkoxybenzyloxopyrimidines (DABOs), a new class of nonnucleoside reverse transcriptase inhibitors, were found to selectively inhibit the HIV-1 multiplication in vitro.Among the C-5 H-substituted 6-benzyl-3,4-dihydro-4-oxopyrimidines, the introduction of alkylthio or cycloalkylthio substituents at C-2 of the pyrimidine ring led to derivatives (S-DABOs) which were up to 10-fold more potent than the alkoxy or cycloalkyloxy counterparts.The further introduction of a methyl group at the 3'-position of the benzyl portion of 2-(alkylthio)-6-benzyluracils reduced the cytotoxicity leading to more selective compounds.Among C-5 methyl-substituted S-DABOs, numerous derivatives showed EC50 values as low as 0.6 μM and lacked cytotoxicity at doses as high as 300 μM.In the C-5 double methyl-substituted series, a more pronounced cytotoxicity was observed and the further introduction of a methyl at the 3'-position in the benzylidene group resulted in total loss of antiviral activity.S-DABOs, namely 2-(alkylthio)-6-benzyl-3,4-dihydro-4-oxopyrimidines, were synthesized by reacting proper methyl (phenylacetyl)acetates or their 2-methyl compounds with thiourea to afford 6-benzyl-4-oxo-1,2,3,4-tetrahydro-2-thiaoxopyrimidines or the related 5-methyl derivatives.Treatment of the latter derivatives with alkyl or cycloalkyl halides in alkaline medium gave the required title compounds.
