In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine).
نویسندگان
چکیده
Ideally, an anti-HIV drug should (1) be highly active against wild-type and mutant HIV without allowing breakthrough; (2) have high oral bioavailability and long elimination half-life, allowing once-daily oral treatment at low doses; (3) have minimal adverse effects; and (4) be easy to synthesize and formulate. R278474, a new diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI), appears to meet these criteria and to be suitable for high compliance oral treatment of HIV-1 infection. The discovery of R278474 was the result of a coordinated multidisciplinary effort involving medicinal chemists, virologists, crystallographers, molecular modelers, toxicologists, analytical chemists, pharmacists, and many others.
منابع مشابه
Molecular dynamics study of non-nucleoside reverse transcriptase inhibitor 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (TMC278/rilpivirine) aggregates: correlation between amphiphilic properties of the drug and oral bioavailability.
The non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278/rilpivirine is an anti-AIDS therapeutic agent with high oral bioavailability despite its high hydrophobicity. Previous studies established a correlation between ability of the drug molecule to form stable, homogeneous populations of spherical nanoparticles (approximately 100-120 nm in diameter) at low pH in surfactant-independent...
متن کاملSynthesis of some new thioxoquinazolinone derivatives and a study on their anticonvulsant and antimicrobial activities.
OBJECTIVE A series of ten novel derivatives of 3-substituted-2-thioxoquinazolin-4(3H)-ones have been synthesized from anthranilic acid via Mannich reaction with various secondary amines in presence of formaldehyde in ice cold condition. MATERIALS AND METHODS The structure of these compounds have been elucidated by spectral (FTIR, 1H-NMR and mass) analysis. The titled compounds were evaluated ...
متن کاملSynthesis and molecular docking of novel N-((2-chloroquinolin-3-yl) methylene)-4-methylbenzenamine derivatives as anti-HIV-1 reverse transcriptase inhibitors
In this research work, a proficient method has been developed for the preparation of novel N-((2-chloroquinolin-3-yl) methylene)-4-methylbenzenamine derivatives from 2-chloroquinoline-3-carbaldehyde derivatives and p-toluidine in ethanol as solvent and using catalytic amount of acetic acid under reflux conditions to obtain desired products in good yields. The identification of all the synthesiz...
متن کاملSynthesis, anti-inflammatory and analgesic evaluation of thioxoquinazolinone derivatives.
A series of 3-substituted-2-thioxoquinazolin-4(3H)-one derivatives have been synthesized and their structures have been elucidated on the basis of IR, (1)H-NMR, elemental analysis and mass spectroscopic studies. Anti-inflammatory and analgesic activity of the synthesized compounds was evaluated by Carrageenan induced rat paw edema method and Eddy's hot plate method respectively. Among the synth...
متن کاملSynthesis and Characterization of Novel Soluble Aromatic Polyesters with Pendant Cyano Groups
2, 6-Bis (4-carboxyphenoxy) benzonitrile was first synthesized by condensation of 2, 6-difluorobenzonitrile with p-Hydroxybenzoic acid in the presence of KOH and DMSO. And then the reaction of 2, 6-bis (4-carboxyphenoxy) benzonitrile with sulfur oxychloride yieded 2, 6-bis (4-chloroformylphenoxy) benzonitrile (BClPOBN). A series of novel soluble aromatic polyesters with pendant cyano groups wer...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of medicinal chemistry
دوره 48 6 شماره
صفحات -
تاریخ انتشار 2005