329187-59-9

Usage

Chemical Properties

N/A

Uses

Intermediate in the preparation of HIV replication inhibitors

InChI:InChI=1/C11H6Cl2N4/c12-9-5-10(13)17-11(16-9)15-8-3-1-7(6-14)2-4-8/h1-5H,(H,15,16,17)

Upstream product

• 873-74-5 4-Aminobenzonitrile 
• 5637-42-3 1-(4-cyanophenyl)guanidine 
• 56-05-3 2-Amino-4,6-dichloropyrimidine 
• 1194-02-1 4-fluorobenzonitrile 
• 623-03-0 4-Cyanochlorobenzene 
• 3764-01-0 2,4,6-trichloropyrimidine 
• 373690-68-7 4-cyanophenyl guanidine hydrochloride 
• 374067-80-8 4-((4,6-dihydroxypyrimidine-2-yl)amino)benzonitrile 

Downstream Products

• 903593-76-0 C₂₀H₁₅ClN₆ 
• 1037445-47-8 C₂₂H₁₇ClN₆ 
• 269055-75-6 4-[[(5-bromo-4,6-dichloro)-2-pyrimidinyl]amino]benzonitrile 
• 1070377-34-2 4-[[6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-benzonitrile 
• 1452006-62-0 4-((4-(mesitylamino)-6-(3-morpholinopropoxy) pyrimidin-2-yl)amino)benzonitrile 
• 244767-67-7 dapivirine 
• 1452006-59-5 4-((4-(mesitylamino)-6-(2-morpholinoethoxy)pyrimidin-2-yl)amino)benzonitrile 
• 1452007-28-1 4-(4-chloro-6-(mesitylamino)pyrimidin-2-ylamino)benzonitrile 
• 1398507-09-9 4-((4-amino-5-bromo-6-chloropyrimidin-2-yl)amino)benzonitrile 
• 1231185-22-0 C₂₁H₁₆N₆O 
• 1231185-21-9 C₂₀H₁₂ClN₅O 
• 903593-80-6 C₂₀H₁₄ClN₅S 
• 269055-15-4 etravirine 

Relevant academic research and scientific papers

Preparation method of 4-[(4,6-dichloro-2-pyrimidinyl)amino]cyanophenyl

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.

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

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.

Process for the Synthesis of Etravirine and Its Intermediates

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.

PROCESS FOR ETRAVIRINE INTERMEDIATE AND POLYMORPHS OF ETRAVIRINE

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.

Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility

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.

A PROCESS FOR ETRA VIRINE INTERMEDIATE AND POLYMORPHS OF ETRAVIRINE

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.

Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues

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.