The pharmaceutical industry has to tackle the explosion of high amounts of poorly soluble APIs. This phenomenon leads to numerous sophisticated solutions. These include the use of multifactorial data analysis identifying correlations between the components and dosage form properties, laboratory and production process parameters with respect to the API liberation Example of such API is bicalutamide. Improved liberation is achieved by particle size reduction. Laboratory batches, with different PSD of API, were filled into gelatinous capsules and consequently granulated for tablet compression. Comparative dissolution profiles with Casodex 150 mg (Astra Zeneca) were performed. The component analysis was used for the statistical evaluation of f1 and f2 factors and D(v,0.9) and D[4,3] parameters of PSD to identify optimal PSD values. Suitable PSD limits for API were statistically confirmed in laboratory and in commercial scale with respect to optimized tablet properties. The tablets were bioequivalent with originator (n = 20; 90% CI for ln AUC0-120: 99.8-111.9%; 90% CI for ln cmax: 101.1-112.9%). In conclusion, the micronisation of the API is still an efficient and inexpensive method improving the bioavailability, although there are more complicated and expensive methods available. Statistical multifactorial methods improved the safety and reproducibility of production.
- MeSH
- anilidy chemická syntéza metabolismus MeSH
- biologická dostupnost MeSH
- chemie farmaceutická metody MeSH
- multivariační analýza MeSH
- nitrily chemická syntéza metabolismus MeSH
- tablety MeSH
- terapeutická ekvivalence MeSH
- tosylové sloučeniny chemická syntéza metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R=3,4-Cl), 9 (R=2-Cl) and 11 (R=4-CF3) showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC=6.25 µg/mL). It was found that the lipophilicity is important for antimycobacterial activity and the best substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig's plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R=3-CF3), 3 (R=3,4-Cl) and 11 (R=4-CF3). A linear dependence between lipophilicity and herbicidal activity was observed.
- MeSH
- antituberkulotika chemická syntéza farmakologie MeSH
- chloroplasty účinky léků metabolismus MeSH
- fotosyntéza účinky léků MeSH
- halogenace MeSH
- herbicidy chemická syntéza farmakologie MeSH
- inhibiční koncentrace 50 MeSH
- mikrobiální testy citlivosti MeSH
- mikrovlny MeSH
- Mycobacterium smegmatis účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- nitrily chemická syntéza farmakologie MeSH
- pyraziny chemická syntéza farmakologie MeSH
- Spinacia oleracea účinky léků metabolismus MeSH
- transport elektronů účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Bosutinib is a selective kinase inhibitor introduced in 2012 by Pfizer Co. for treatment of chronic myeloid leukemia. Bosutinib is widely used in medicine and basic research. Some information indicated that researchers purchasing Bosutinib from a wide range of sources may have unwittingly been using an isomer of Bosutinib instead of Bosutinib itself. The aim of the review is to describe this serious case of marketing as well as to outline possible reasons and consequences of this case.
- MeSH
- aniliny chemická syntéza chemie zásobování a distribuce MeSH
- chemické techniky analytické metody přístrojové vybavení využití MeSH
- chinoliny chemická syntéza MeSH
- chronická myeloidní leukemie * farmakoterapie MeSH
- farmaceutická technologie MeSH
- farmaceutický průmysl MeSH
- isomerie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie metody přístrojové vybavení MeSH
- medikační omyly MeSH
- nitrily chemická syntéza MeSH
- protoonkogenní proteiny c-abl * antagonisté a inhibitory chemická syntéza terapeutické užití MeSH
- skupina kinas odvozených od src-genu * antagonisté a inhibitory chemická syntéza terapeutické užití MeSH
- Check Tag
- lidé MeSH
This paper describes preparation and biological evaluation of pyrazinamide analogues. Pyrazinamide with its simple structure gives a good opportunity for further modification regarding an increase of its antimycobacterial activity. We prepared a series of compounds derived from pyrazine-2,5-dicarbonitrile with arylamino substitution in position 3. All compounds were assayed in vitro against major Mycobacterium and various Fungi species. The best activity was found in 3-{[3-(trifluoromethyl)phenyl]amino}pyrazine-2,5-dicarbonitrile 11 with the value of 6.25 micromol(-1) against M. tuberculosis H(37)Rv and moderate activity against minor Mycobacterium pathogens.
- MeSH
- Absidia účinky léků MeSH
- antifungální látky farmakologie chemická syntéza MeSH
- antituberkulotika farmakologie chemická syntéza MeSH
- Aspergillus fumigatus účinky léků MeSH
- Candida účinky léků MeSH
- financování organizované MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium účinky léků MeSH
- nitrily farmakologie chemická syntéza MeSH
- pyrazinamid analogy a deriváty farmakologie chemická syntéza MeSH
- pyraziny farmakologie chemická syntéza MeSH
- Trichosporon účinky léků MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- vztahy mezi strukturou a aktivitou MeSH
Three asymmetrical AChE reactivators with cyano-moiety and propane linker were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by nerve agent tabun and insecticide paraoxon was tested in vitro and compared to pralidoxime, HI-6, obidoxime, K027, and K048. According to the results, three compounds seem to be promising against paraoxon-inhibited AChE. Better results were obtained for bisquaternary substances at least with one oxime group in position four. None of tested substances was able to satisfactorily reactivate tabun-inhibited AChE at concentration applicable for in vivo experiments.
