- Preparation method of 4-[(4,6-dichloro-2-pyrimidinyl)amino]cyanophenyl
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The invention provides a method for synthesizing 4-[(4,6-dichloro-2-pyrimidinyl)amino]cyanophenyl (III). The method comprises the steps that 2-amino-4,6-dichloropyrimidine (II) is taken as a raw material to be mixed with 4-fluorobenzonitrile (I) in the presence of sodium hydride, and a one-step method is adopted for synthesis. The method for synthesizing the 4-[(4,6-dichloro-2-pyrimidinyl)amino]cyanophenyl (III) has the advantages that the operation is simple, the purity and yield of the product are higher, and industrialized practical significance and social and economic benefits are provided.
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Paragraph 0023-0028
(2019/11/14)
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- The discovery of novel diarylpyri(mi)dine derivatives with high level activity against a wide variety of HIV-1 strains as well as against HIV-2
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By means of structure-based molecular hybridization strategy, a series of novel diarylpyri(mi)dine derivatives targeting the entrance channel of HIV-1 reverse transcriptase (RT) were designed, synthesized and evaluated as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs). Encouragingly, all the tested compounds showed good activities against wild-type (WT) HIV-1 (IIIB) with EC50 in the range of 1.36 nM–29 nM, which is much better than those of nevirapine (NVP, EC50 = 125.42 nM) and azidothymidine (AZT, EC50 = 11.36 nM). Remarkably, these compounds also displayed effective activity against the most of the single and double-mutated HIV-1 strains with low EC50 values, which is comparable to the control drugs. Besides, these compounds were also exhibited favorable enzymatic inhibitory activity. Moreover, preliminary structure-activity relationships (SARs) and molecular modeling study were investigated and discussed in detail. Unexpectedly, four diarylpyrimidines yielded moderate anti-HIV-2 activities. To our knowledge, this is rarely reported that diarylpyrimidine-based NNRTIs have potent activity against both HIV-1 and HIV-2 in cell culture.
- Lu, Xueyi,Yang, Jiapei,Kang, Dongwei,Gao, Ping,Daelemans, Dirk,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
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p. 2051 - 2060
(2018/03/23)
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- Process for the Synthesis of Etravirine and Its Intermediates
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The invention discloses the synthesis of Etravirine via intermediate 4-((4-amino-5-bromo-6-chloropyrimidin-2-yl) amino)benzonitrile and process for the preparation of Etravirine of the formula-I.
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- Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility
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Non-nucleoside inhibitors of HIV-1 reverse transcriptase are reported that have ca. 100-fold greater solubility than the structurally related drugs etravirine and rilpivirine, while retaining high anti-viral activity. The solubility enhancements come from strategic placement of a morpholinylalkoxy substituent in the entrance channel of the NNRTI binding site. Compound 4d shows low-nanomolar activity similar to etravirine towards wild-type HIV-1 and key viral variants.
- Bollini, Mariela,Cisneros, José A.,Spasov, Krasimir A.,Anderson, Karen S.,Jorgensen, William L.
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p. 5213 - 5216
(2013/09/12)
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- PROCESS FOR ETRAVIRINE INTERMEDIATE AND POLYMORPHS OF ETRAVIRINE
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4-[[6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-benzonitrile is a key intermediate for the preparation of etravirine. The present invention provides a process for preparation of 4-[[6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethylbenzonitrile. The present invention also provides a novel process for the preparation of etravirine crystalline form I. The present invention further provides novel crystalline forms of etravirine, processes for their preparation and pharmaceutical compositions comprising them.
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- A PROCESS FOR ETRA VIRINE INTERMEDIATE AND POLYMORPHS OF ETRAVIRINE
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4-[[6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl- benzonitrile is a key intermediate for the preparation of etravirine. The present invention provides a process for preparation of 4-[[6-chloro-2-[(4-cyanophenyl)amino]-4- pyrimidinyl]oxy]-3,5-dimethylbenzonitrile. The present invention also provides a novel process for the preparation of etravirine crystalline form I. The present invention further provides novel crystalline forms of etravirine, processes for their preparation and pharmaceutical compositions comprising them.
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- Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues
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The synthesis and anti-HIV-1 activity of a series of diarylpyrimidines (DAPYs) are described. Several members of this novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) are extremely potent against both wild-type and a panel of clinically significant single- and double-mutant strains of HIV-1.
- Ludovici, Donald W.,De Corte, Bart L.,Kukla, Michael J.,Ye, Hong,Ho, Chih Y.,Lichtenstein, Mark A.,Kavash, Robert W.,Andries, Koen,De Bethune, Marie-Pierre,Azijn, Hilde,Pauwels, Rudi,Lewi, Paul J.,Heeres, Jan,Koymans, Lucien M.H.,De Jonge, Marc R.,Van Aken, Koen J.A.,Daeyaert, Frederik F.D.,Das, Kalyan,Arnold, Edward,Janssen, Paul A.J.
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p. 2235 - 2239
(2007/10/03)
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