1609687-15-1

Basic information

• Product Name: (E)-3-(4-amino-3-fluoro-5-methylphenyl)acrylonitrile
• Synonyms: (E)-3-(4-amino-3-fluoro-5-methylphenyl)acrylonitrile
• CAS NO: 1609687-15-1
• Molecular Weight: 176.193
• Mol File: 1609687-15-1.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: (E)-3-(4-amino-3-fluoro-5-methylphenyl)acrylonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: (E)-3-(4-amino-3-fluoro-5-methylphenyl)acrylonitrile(1609687-15-1)
• EPA Substance Registry System: (E)-3-(4-amino-3-fluoro-5-methylphenyl)acrylonitrile(1609687-15-1)

Safety Data

• Hazardous Substances Data: 1609687-15-1(Hazardous Substances Data)

Upstream product

• 107-13-1 acrylonitrile 
• 443-89-0 2-fluoro-6-methylaniline 
• 429683-46-5 4-bromo-2-fluoro-6-methylbenzeneamine 

Relevant articles and documents

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.

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.