500292-86-4

Usage

Function

Potent and selective inhibitor of Rho kinase (ROCK)

Biological Role

Regulates smooth muscle contraction and cell motility

Medical Applications

Treatment of cerebral vasospasm after subarachnoid hemorrhage
Management of pulmonary hypertension
Therapy for coronary artery disease
Potential treatment for ischemic stroke
Potential treatment for neurodegenerative diseases

Additional Properties

Anti-inflammatory effects
Anti-fibrotic effects
Potential for treating a range of diseases beyond cardiovascular and neurological disorders

Upstream product

• 4102-53-8 4-iodo-2,6-dimethylaniline 
• 107-13-1 acrylonitrile 
• 24596-19-8 4-bromo-2,6-dimethylphenylamine 
• 88-05-1 2,4,6-trimethylaniline 
• 661489-23-2 (2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile hydrochloride 
• 87-62-7 2,6-dimethylaniline 
• 749249-96-5 C₁₁H₁₀N₂O₂ 
• 500292-92-2 (2E)-3-(4-amino-3,5-dimethylphenyl)prop-2-enamide 
• 75-05-8 acetonitrile 
• 661489-23-2 C₁₁H₁₂N₂*(x)ClH 
• 64-17-5 ethanol 
• 114886-15-6 N'-(4-bromo-2,6-dimethylphenyl)-N,N-dimethylmethanimidamide 

Downstream Products

• 700361-47-3 Rilpivirine hydrochloride 
• 1609687-08-2 4-{(6-[(4-2-cyanovinyl-2,6-dimethylphenyl)amino]pyridin-2-yl)amino}benzonitrile 
• 1609687-27-5 4-{(6-[(4-2-cyanovinyl-2,6-dimethylphenyl)amino]pyridin-2-yl)amino}benzonitrile 
• 1609686-99-8 4-{5-[4-(2-cyanovinyl)-2,6-dimethylphenyl]amino}-2-fluorophenylaminobenzonitrile 
• 1609687-29-7 4-{5-[4-(2-cyanovinyl)-2,6-dimethylphenyl]amino}-2-fluorophenylaminobenzonitrile 
• 1609686-83-0 3-{4-[6-(4-chlorophenyl)amino-5-fluoropyridin-2-yl]amino-3,5-dimethylphenyl}acrylonitrile 

Relevant academic research and scientific papers

Cu-catalyzed cyanomethylation of imines and α,β-alkenes with acetonitrile and its derivatives

We describe copper-catalyzed cyanomethylation of imines and α,β-alkenes with a methylnitrile source and provide an efficient route to synthesize arylacrylonitriles and β,γ-unsaturated nitriles. This method tolerates aliphatic and aromatic alkenes substituted with a variety of functional groups such as F, Cl, Br, Me, OMe,tert-Bu, NO2, NH2and CO2H with good to excellent yields (69-98%). These systems consist of inexpensive, simple copper catalyst and acetonitrile with its derivatives (α-bromo/α-iodo-acetonitrile) and are highly applicable in the industrial production of acrylonitriles.

Synthetic method of rilpivirine intermediate

The invention provides a synthetic method of a rilpivirine intermediate. The synthesis method includes: taking 2, 4, 6-trimethylaniline as the raw material to react with 2, 3-dichloro-5, 6-dicyanobenzoquinone (DDQ) in a diluted hydrochloric acid solution

PROCESS FOR THE PREPARATION OF RILPIVIRINE

The present invention relates to a new process of preparation of Rilpivirine, or a pharmaceutically acceptable salt thereof. Another aspect of the invention concerns compounds of formulae II and III: and their salts thereof, and their use for the preparation of Rilpivirine or a suitable salt thereof.

Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles

Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 μL/min/mg (human) and 33.2 μL/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 μL/min/mg; rat, 33.2 μL/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.

Pyrimidine heterocyclic compounds, pyrimidine heterocyclic compound salts, and preparation method and application thereof

The invention provides pyrimidine heterocyclic compounds, pyrimidine heterocyclic compound salts, and a preparation method and application thereof. According to the pyrimidine heterocyclic compounds provided by the invention, specific Rq is selected, so that the obtained compounds have favorable drug resistance and long half life when being used as the medicine for treating or preventing HIV. The compounds have the advantages of high activity, low toxicity and high stability.

Rilpivirine midbody preparing technology

The invention belongs to the field of medicinal chemistry, and particularly relates to a rilpivirine midbody preparing technology. The technology comprises the steps that 1, 4-bromo-2,6-dimethylaniline and acrylonitrile react under the catalysis of pallad

A METHOD OF PRODUCING HIGHLY PURE RILPIVIRINE AND ITS SALTS

A method of preparing Rilpivirine of formula I, or a suitable salt thereof, comprising a reaction of a hydrogen halide of the aniline derivative of formula II with chloropyrimidine of formula III in methyl isobutyl ketone and in the presence of a polar additive.

2,6-Di(arylamino)-3-fluoropyridine Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors

New non-nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier described di(arylamino)pyrimidines but featuring a 2,6-di(arylamino)-3-fluoropyridine, 2,4-di(arylamino)-5-fluoropyrimidine, or 1,3-di(arylamino)-4-fluorobenzene moiety instead of a 2,4-disubstituted pyrimidine moiety, are reported. The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations as the key steps. It is demonstrated through direct comparison with reference compounds that the presence of a fluorine atom increases the in vitro anti-HIV activity, both against the wild type virus and drug-resistant mutant strains.

Pharmaceutical compositions comprising a basic drug compound, a surfactant, and a physiologically tolerable water soluble acid

The invention provides a novel pharmaceutical composition comprising a basic respectively acidic drug compound, a surfactant and a physiologically tolerable water-soluble acid respectively base characterized in that the acid respectively base:drug compound ratio is at least 1:1 by weight.

NOVEL ANTI-HIV COMPOUNDS

The present invention relates to the field of HIV-1 infections, and in particular provides novel compounds containing fluorine on the Central ring. The compounds according to this invention are very suitable for the prevention and/or treatment of HIV-1 infection and in particular show higher activity against NNRTI-resistant strains of HIV-1.