244768-32-9

Usage

Uses

Used in Pharmaceutical Industry:
4-N[2(4-CHLOROPYRIMIDINYL)]-AMINO BENZONITRILE is used as a key intermediate in the synthesis of 2-naphthyl substituted diarylpyrimidines (DAPY) analogues for the development of novel therapeutic agents. These DAPY analogues have shown potential in targeting various diseases, including cancer, due to their unique chemical structure and biological activity.
Used in Cancer Treatment:
4-N[2(4-CHLOROPYRIMIDINYL)]-AMINO BENZONITRILE is used as a precursor in the development of DAPY analogues, which have demonstrated potential in the treatment of various types of cancer. These analogues can modulate multiple oncological signaling pathways, leading to the inhibition of tumor growth and progression. Additionally, they may exhibit synergistic effects when combined with conventional chemotherapeutic drugs, enhancing chemo-sensitivity and efficacy in resistant cases.
Used in Drug Delivery Systems:
To improve the delivery, bioavailability, and therapeutic outcomes of DAPY analogues, novel drug delivery systems have been developed. These systems employ various organic and metallic nanoparticles as carriers for the delivery of DAPY analogues, which are synthesized using 4-N[2(4-CHLOROPYRIMIDINYL)]-AMINO BENZONITRILE as a key intermediate. This approach aims to overcome the limitations of the compound and enhance its applications in the pharmaceutical industry.

InChI:InChI=1/C11H7ClN4/c12-10-5-6-14-11(16-10)15-9-3-1-8(7-13)2-4-9/h1-6H,(H,14,15,16)

Upstream product

• 189956-45-4 4-[(4-hydroxy-2-pyrimidinyl)amino]benzonitrile 
• 873-74-5 4-Aminobenzonitrile 
• 1228671-28-0 4-((4-methoxypyrimidin-2-yl)amino)benzonitrile 
• 5637-42-3 1-(4-cyanophenyl)guanidine 

Downstream Products

• 374067-85-3 4-((4-((4-bromo-2,6-dimethylphenyl)amino)pyrimidin-2-yl)amino)benzonitrile 
• 1066549-62-9 4-(4-{4-[5-(hydroxyiminomethyl)furan-2-yl]-2,6-dimethylphenylamino}pyrimidin-2-ylamino)benzonitrile 
• 748150-43-8 C₂₀H₁₄N₄O₂ 
• 748150-50-7 C₂₂H₁₅ClN₆ 
• 748150-55-2 C₂₂H₁₅ClN₆ 
• 269055-72-3 4-[(5-bromo-4-chloro-2-pyrimidinyl)amino]benzonitrile 
• 1232683-99-6 C₂₀H₁₅N₅ 
• 1232185-18-0 C₂₀H₁₅N₅ 
• 1353160-27-6 C₂₃H₁₅N₅ 
• 1232684-01-3 C₁₉H₁₂BrN₅ 
• 1334320-19-2 C₁₉H₁₂FN₅ 
• 1334320-18-1 C₁₉H₁₂FN₅ 
• 1353160-30-1 C₂₃H₁₅N₅ 
• 1334320-20-5 C₁₉H₁₂FN₅ 

Relevant academic research and scientific papers

Structural modifications of diarylpyrimidines (DAPYs) as HIV-1 NNRTIs: Synthesis, anti-HIV activities and SAR

30 new analogues of diarylpyrimidines were synthesized for further structural modifications, involving not only the linker but also the wing α of DAPYs. The anti-HIV-1 activities of all target molecules were evaluated, and most of them exhibited potent anti-HIV-1 (WT) activities and low cytotoxicities. Among which, compound 4g showed excellent activities against WT HIV-1 with an EC50 value of 5.8?nM and SI of up to 26,034. Another compound 4ab bearing a novel pyridinyl Wing α also displayed attractive activities. The structure-activity relationship (SAR) study was also summarized.

A novel family of diarylpyrimidines (DAPYs) featuring a diatomic linker: Design, synthesis and anti-HIV activities

To improve the conformational flexibility and positional adaptability of the traditional diarylpyrimidines (DAPYs), a family of diarylpyrimidines featuring a C-N diatomic linker between the left wing benzene ring and the central pyrimidine was firstly des

Design of biphenyl-substituted diarylpyrimidines with a cyanomethyl linker as HIV-1 NNRTIs via a molecular hybridization strategy

The key problems of human immunodeficiency virus (HIV) therapy are the rapid emergence of drug-resistant mutant strains and significant cumulative drug toxicities. Therefore, there is an urgent demand for new anti-HIV agents with low toxicity and broad-spectrum antiviral potency. A series of biphenyl-substituted diarylpyrimidines with a cyanomethyl linker were designed using a molecular hybridization strategy. The cell-based anti-HIV assay showed that most of the compounds exhibited moderate to good activities against wild-type HIV-1 and clinically relevant mutant strains with a more favorable toxicity, and the enzymatic assay showed they had nanomolar activity against reverse transcriptase (RT). Compound 10p exhibited the best activity against wild-type HIV-1 with an EC50 (50% HIV-1 replication inhibitory concentration) value of 0.027 μM, an acceptable CC50 (50% cytotoxic concentration) value of 36.4 μM, and selectivity index of 1361, with moderate activities against the single mutants (EC50: E138K, 0.17 μM; Y181C, 0.87 μM; K103N, 0.9 μM; L100I, 1.21 μM, respectively), and an IC50 value of 0.059 μM against the RT enzyme, which was six-fold higher than nevirapine (NVP). The preliminary structure–activity relationship (SAR) of these new compounds was concluded. The molecular modeling predicted the binding modes of the new compounds with RT, providing molecular insight for further drug design.

Exploiting the hydrophobic channel of the NNIBP: Discovery of novel diarylpyrimidines as HIV-1 NNRTIs against wild-type and K103N mutant viruses

To further explore the chemical space surrounding the “hydrophobic channel” of the NNRTI binding pocket (NNIBP), a new series of diarylpyrimidines (DAPYs) were designed and synthesized as potent HIV-1 non-nucleoside RT inhibitors (NNRTIs). The target comp

Design, synthesis, and antiviral evaluation of novel piperidine-substituted arylpyrimidines as HIV-1 NNRTIs by exploring the hydrophobic channel of NNIBP

Herein, alkenylpiperidine and alkynylpiperidine moieties were introduced into the left wing of DAPYs (diarylpyrimidines) to explore the new site of the NNIBP (non-nucleoside inhibitor binding pocket) protein-solvent interface region via the structure-based drug design strategy. All the synthesized compounds displayed nanomolar to submicromolar activity against WT (wild-type) HIV-1. Among all, compound FT1 (EC50 = 19 nM) was found to be the most active molecule, which is better than NVP (EC50 = 0.10 μM). In addition, most of the compounds displayed micromolar activity against K103N and E138K mutant strains, while FT1 (EC50(K103N) = 50 nM, EC50(E138K) = 0.19 μM) still has the most effective activity. The molecular dynamics simulation studies revealed that the presence of pyridine moiety of FT1 was essential and played a significant role in its binding with RT (reverse transcriptase).

Scaffold hopping in discovery of HIV-1 non-nucleoside reverse transcriptase inhibitors: From CH(CN)-DABOs to CH(CN)-dapys

Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds B4 (EC50 = 6 nM) and B6 (EC50 = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC50 values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 μM). The preliminary structure-activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.

Substituted 1,2,3 triazole diarylpyrimidine derivative as well as preparation method and application thereof

The invention discloses a substituted 1,2,3 triazole diarylpyrimidine derivative as well as a preparation method and application thereof. The substituted 1,2,3 triazole diarylpyrimidine derivative orpharmaceutically acceptable salts or prodrugs thereof ha

Targeting the hydrophobic channel of NNIBP: Discovery of novel 1,2,3-triazole-derived diarylpyrimidines as novel HIV-1 NNRTIs with high potency against wild-type and K103N mutant virus

Enlightened by our previous efforts to modify diarylpyrimidines as HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) and the reported crystallographic studies, we designed and synthesized novel 1,2,3-triazole-derived diarylpyrimidine der

Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored "hydrophobic channel"

A new series of diarylpyrimidines (DAPYs) were designed, synthesized and evaluated as novel HIV-1 NNRTIs to further explore the chemical space surrounding the "hydrophobic channel" of the NNRTI binding pocket (NNIBP), guided by the comprehensive analysis

Discovery of biphenyl-substituted diarylpyrimidines as non-nucleoside reverse transcriptase inhibitors with high potency against wild-type and mutant HIV-1

A novel series of diarylpyrimidine (DAPY) derivatives bearing the biphenyl motif with multiple substituted groups was synthesized as human immunodeficiency virus (HIV)-1 non-nucleoside reverse transcriptase inhibitors. All of the target compounds were evaluated for their in vitro activity against HIV in MT-4 cells. Most of the compounds exhibited excellent activity with low nanomolar EC50 values against wild-type, single and double mutant HIV-1 strains. Compound 4b displayed an EC50 value of 1 nM against HIV-1 IIIB, 1.3 nM against L100I, 0.84 nM against K103 N, 1.5 nM against Y181C, 11 nM against Y188L, 2 nM against E138K, 10 nM against K103 N + Y181C, and almost 110 nM against F227L + V106. The improvement in the selectivity and potency of the target molecules against the wild-type and mutant HIV-1 strains validated our hypothesis. The biphenyl ring in the DAPY derivatives could strengthen the π-π stacking effect between the target molecule and the non-nucleoside inhibitor-binding pocket in the reverse transcriptase by extending the conjugating systems. This research represented a significant step toward the discovery of novel therapeutic DAPYs for treating acquired immunodeficiency syndrome in patients infected with HIV-1.