Showing papers by "Josef Jampilek published in 2010"
TL;DR: In this study, a series of fourteen ring-substituted 8-hydroxyquinoline derivatives were prepared and showed biological activity comparable with or higher than the standards isoniazid or fluconazole.
Abstract: In this study, a series of fourteen ring-substituted 8-hydroxyquinoline derivatives were prepared. The synthesis procedures are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than the standards isoniazid or fluconazole. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.
47 citations
TL;DR: Several quinazolinone and styrylquinazoline analogues were found to have markedly greater anti-proliferative activity than desferoxamine and cis-platin.
43 citations
TL;DR: In this study, a series of twelve ring-substituted salicylanilides and carbamoylphenylcarbamates were prepared and characterized and showed minimal anti-proliferative activity against human cells in culture, indicating they would have low cytotoxicity.
Abstract: In this study, a series of twelve ring-substituted salicylanilides and carbamoylphenylcarbamates were prepared and characterized. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Moreover, their site of action in the photosynthetic apparatus was determined. Primary in vitro screening of the synthesized compounds was also performed against mycobacterial, bacterial and fungal strains. Several compounds showed biological activity comparable with or higher than the standards 3-(3,4-dichlorophenyl)-1,1-dimethylurea, isoniazid, penicillin G, ciprofloxacin or fluconazole. The most active compounds showed minimal anti-proliferative activity against human cells in culture, indicating they would have low cytotoxicity. For all compounds, the relationships between lipophilicity and the chemical structure are discussed.
41 citations
TL;DR: A series of sixteen pyrazinamide analogues with the -CONH- linker connecting the pyrazine and benzene rings was synthesized by the condensation of chlorides of substituted pyrazINEcarboxylic acids with ring-substituted (chlorine) anilines for antimycobacterial and antifungal activity and for their ability to inhibit photosynthetic electron transport (PET).
Abstract: A series of sixteen pyrazinamide analogues with the -CONH- linker connecting the pyrazine and benzene rings was synthesized by the condensation of chlorides of substituted pyrazinecarboxylic acids with ring-substituted (chlorine) anilines. The prepared compounds were characterized and evaluated for their antimycobacterial and antifungal activity, and for their ability to inhibit photosynthetic electron transport (PET). 6-Chloro-N-(4-chlorophenyl)pyrazine-2-carboxamide manifested the highest activity against Mycobacterium tuberculosis strain H37Rv (65% inhibition at 6.25 μg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 6-chloro-5-tert-butyl-N-(3,4-dichlorophenyl)pyrazine-2-carboxamide (MIC=62.5 μmol/L). 6-chloro-5-tert-butyl-N-(4-chlorophenyl)pyrazine-2-carboxamide showed the highest PET inhibition in spinach chloroplasts (Spinacia oleracea L.) chloroplasts (IC50=43.0 μmol/L). For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds as well as their structure-activity relationships are discussed.
38 citations
Patent•
13 Jan 2010
TL;DR: Co-crystals of inhibitors of tyrosine kinases, especially of Imatinib mesylate, have been found as a suitable form of API for dosage forms, both conventional and with controlled release for medicaments of the second generation as discussed by the authors.
Abstract: Co-crystals of inhibitors of tyrosine kinases, especially of Imatinib mesylate, have been found as a suitable form of API for dosage forms, both conventional and with controlled release for medicaments of the second generation. Complexes of kinase inhibitors with functionalized polysaccharides form solid dispersions suitable for pharmaceutical applications.
20 citations
TL;DR: The series of seven esters of substituted 6-aminohexanoic acid as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented here.
17 citations
TL;DR: Two series of esters were generated by multi-step synthesis with substituted 6-aminohexanoic acid as potential transdermal penetration enhancers and showed higher enhancement ratios than oleic acid and showed minimal anti-proliferative activity, indicating they would have low cytotoxicity when administered as chemical penetration enhancer.
8 citations
TL;DR: The relationships between the chemical structures of the studied compounds required for co-crystal generation are discussed and new entities of ibandronate monosodium salt with phenyl-β-d-galactopyranoside were found and characterized.
Abstract: Mixtures of ibandronate monosodium salt with eleven gluco- and/or galacto-pyranoside derivatives as counterions were designed to prepare co-crystals with improved intestinal absorption. In general, gastrointestinal absorption of bisphosphonates after oral administration is approximately 1%. Co-crystals were generated by means of thermodynamically and/or kinetically controlled crystallization processes. Seventy-seven prepared samples were analyzed by means of FT-NIR, FT-Raman spectrometry and solid state NMR spectroscopy. New entities of ibandronate monosodium salt with phenyl-β-d-galactopyranoside were found and characterized. The absorption of these potential new co-crystals was investigated by means of PAMPA experiments. In the present study the relationships between the chemical structures of the studied compounds required for co-crystal generation are discussed.
8 citations
TL;DR: The Synthesis of (2E)‐2‐methyl‐3‐(4‐{[4‐(quinolin‐ 2‐ylmethoxy)phenyl]sulfanyl}phenyl) prop‐2-enoic acid and racemic 2‐methyl-3‐ (4‐ {[ 4‐(quinolin‐2•ylmETHoxy) phenyl]phenyl)propanoic acid as new potential antileukotrienic drugs
Abstract: The syntheses of (2E)-2-methyl-3-(4-([4-(quinolin-2-ylmethoxy)phenyl]sulfanyl)phenyl) prop-2-enoic acid (VUFB 20609) and racemic 2-methyl-3-(4-([4-(quinolin-2-ylmethoxy) phenyl]sulfanyl)phenyl)propanoic acid (VUFB 20584) as new potential antileukotrienic drugs are described. Due to a low reactivity of the 4-substituted aryl bromides (coupling of the 4-substituted aryl bromides do not provide an activating functional group with 4-methoxybenzene-1-thiol), special conditions, in particular specific heterogeneous copper catalysts, were used. Catalytic hydrogenation of the conjugated double bond on Pd/C in the presence of the sulfanyl group is discussed. In-vitro cytotoxicity testing was performed using a microplate colorimetric acid phosphatase assay. Antiplatelet activity was evaluated using an in-vitro test in human platelet-rich plasma. Some substances inhibited arachidonic acid-induced platelet aggregation.
8 citations
Patent•
06 Dec 2010
TL;DR: In this paper, a digestive tract simulator, comprising hydraulically interconnected at least two elastic bags (12) kept at the constant temperature and a controllable heating source, is presented.
Abstract: A digestive tract simulator, comprising hydraulically interconnected at least two elastic bags (12) kept at the constant temperature and a controllable heating source, wherein a heating source is represented by a heated temperating plate (2) over whose working surface intended for placing of elastic bags (12) two levers (7) are arranged in an axial distance, swinging around a common axis; to these levers (7) a deflected wing (3) placed in parallel with the temperating plate (2) and having working arms opened in a wide angle in direction from the temperating plate (2) is mounted on the lever's side near to the temperating plate (2); at least one of levers (7) is connected to a pendulum engine (4) having an adjustable motion so that elastic bags (12) are in operating state situated between the working surface of the temperating plate (2) and the deflected wing (3); each of bags (12) is equipped by an air cock (127) and an input and output pipe channel (126) for working medium, connecting bags (12) together via tubing coupled through a peristaltic pump (5).
8 citations
Patent•
25 Nov 2010
TL;DR: In this paper, a method of manufacturing a pharmaceutical composition containing an active substance of the sartan type in the form of an adduct (complex) with a pectin, optionally in a mixture with a glucan, is presented.
Abstract: The present solution relates to a method of manufacturing a pharmaceutical composition containing an active substance of the sartan type in the form of an adduct (complex) with a pectin, optionally in a mixture with a glucan. The resulting adduct is characterized by higher solubility in water as compared with the original pharmaceutically active substance. The adduct (complex) consisting of the active substance and pectin is then used for preparing a dosage form with targeted (controlled) release in the intestine.
31 Oct 2010
Patent•
19 Aug 2010
TL;DR: In this article, a method of preparation of an imatinib mesylate polymorph as an AP1 form suitable for dosage forms is described, and two new polymorphous forms of Imatinib Mesylate are accessible through this method, these forms are named polymorph "Z1" and "Z2".
Abstract: The solution relates to a method of preparation of an imatinib mesylate polymorph as an AP1 form suitable for dosage forms. Formation of new polymorphs of tyrosine kinase inhibitors proceeds depending on the conditions, said method consisting of the following steps: a) preparation of imatinib mesylate by reaction of the imalinib base and methanesulfonic acid in aqueous environment or in a water-organic solvent mixture, with optional addition of an organic solvent; b) addition of an inorganic salt in an aqueous solution, controlling the pH and ionic strength of the solution; c) crystallization process at controlled temperature. The solution also relates to the crystalline form of imatinib mesylate polymorph and use thereof. Two new polymorphous forms of Imatinib mesylate are accessible through this method, these forms are named polymorph "Z1" and "Z2". "Z1 " is characterized by peaks in the XRPD at 5,3; 7,5; 10,0; 10,6; 14,1; 15,0 and 16;6°. "Z2" is characterized by peaks in the XRPD at 5,5; 10,6; 10,9; 14.9; 17,0 and 21,9°.
TL;DR: In this article, the crystal structures of two new AChE reactivators, which are bromides of (E)-1,4-bis(4-hydroxyiminomethylpyridinium)-but-2-ene (K075) and of 4,4′-bis (hydroximinmethyl)1,1′-(1, 4-phenylenedimethyl)-bispyrinium (K114), were described.
Abstract: The investigation of relationships between the molecular structure of the compounds capable to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus toxins, such as nerve agents and pesticides, is an important step toward synthesis of more efficient antidota. In the present article, we describe the crystal structures of two new AChE reactivators, which are bromides of (E)-1,4-bis(4-hydroxyiminomethylpyridinium)-but-2-ene (K075) and of 4,4′-bis(hydroxyiminomethyl)-1,1′-(1,4-phenylenedimethyl)-bispyridinium (K114). Their molecular geometry and intermolecular interactions in the crystalline state are compared to those in the crystal structures of the well-known AChE reactivators, obidoxime, and TMB-4. Inspection of hydrogen bonds and other short intermolecular contacts in the crystalline AChE–obidoxime complex revealed their similarity to those observed in the crystal structures of K075 and K114.
Patent•
13 Jan 2010
TL;DR: In this paper, co-cristaux d'inhibiteurs de tyrosine kinases, specialement de mesylate d'Imatinib, se sont reveles une forme adaptee d'API dans des formes galeniques, classiques comme a liberation controlee, for des medicaments de seconde generation.
Abstract: Des co-cristaux d'inhibiteurs de tyrosine kinases, specialement de mesylate d'Imatinib, se sont reveles une forme adaptee d'API dans des formes galeniques, classiques comme a liberation controlee, pour des medicaments de seconde generation. Des complexes d'inhibiteurs de kinase avec des polysaccharides fonctionnalises forment des dispersions solides adaptees aux applications pharmaceutiques.
Patent•
25 Nov 2010
TL;DR: In this paper, a method of manufacturing a pharmaceutical composition containing an active substance in the form of an adduct (complex) with a pectin, optionally in a mixture with a glucan, was proposed.
Abstract: The present solution relates to a method of manufacturing a pharmaceutical composition containing an active substance in the form of an adduct (complex) with a pectin, optionally in a mixture with a glucan. The resulting adduct is characterized by higher solubility in water as compared with the original pharmaceutically active substance. The adduct (complex) consisting of the active substance and pectin is then used for preparing a dosage form with targeted (controlled) release in the intestine.
22 Oct 2010
TL;DR: In this article, a series of nine 4-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl N-alkyl carbamates was synthesized and analyzed using RP-HPLC to determine lipophilicity.
Abstract: In this study, a series of nine 4-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl N-alkylcarbamates was prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. For the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR).