RESUMO
A selective and sensitive UHPLC-MS/MS bioanalytical method to determine PT-31, an analgesic drug candidate, in rat plasma was developed and validated. Analyses were performed using a UHPLC-MS/MS system equipped with an electrospray ionization interface operating in the positive ionization mode using a C18 reversed-phase column with a mobile phase of water:acetonitrile (68:31, v/v) containing 0.1% acetic acid eluting in a gradient mode with a flow rate of 0.3 mL/min. Plasma samples were deproteinized with cold acetonitrile containing 0.01% TFA (1:2, v/v) and 50 µL of the supernatant were injected into the system. PT-31 and phenytoin (internal standard) retention times were roughly 1.0 and 1.5 min, respectively. Linear standard curves were plotted for the 0.01-10 µg/mL concentration range, with a coefficient of determination > 0.99. The method's precision was over 88%. Maximum intra- and inter-day relative standard deviations were 14.6% and 11.6%, respectively. Interfering substances were not detected in the chromatogram, indicating that the method was specific. PT-31 stability was assessed under different temperature and storage settings. The method was used to characterize PT-31 plasma pharmacokinetics following administration of 5 mg/kg i.v. to Wistar rats. Therefore, the method described is sensitive, linear, precise and specific enough to determine PT-31 in preclinical pharmacokinetic investigations. Copyright © 2015 John Wiley & Sons, Ltd.
Assuntos
Analgésicos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Analgésicos/farmacocinética , Animais , Imidazolidinas/sangue , Imidazolidinas/farmacocinética , Limite de Detecção , Ratos , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
A novel set of acridinylidene thiazolidinediones and benzylidene thiazolidinediones was synthesized by nucleophilic addition of cyanoacrylates. Some of these compounds were evaluated for their glucose lowering capability and their effects on the triglyceride level in alloxan diabetic mice.
Assuntos
Acridinas/síntese química , Compostos de Benzil/síntese química , Hipoglicemiantes/síntese química , Tiazolidinedionas/síntese química , Acridinas/química , Acridinas/farmacologia , Animais , Compostos de Benzil/química , Compostos de Benzil/farmacologia , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/mortalidade , Avaliação Pré-Clínica de Medicamentos , Feminino , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Rosiglitazona , Tiazolidinedionas/química , Tiazolidinedionas/farmacologia , Triglicerídeos/sangueRESUMO
Synthesis and physico-chemical properties of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-ones, 5-benzylidene-3-(4-nitro-benzyl)-2-thioxo-imidazolidin-4-ones and 4-acridin-9-ylmethylene-1-benzyl-5-thioxo-imidazolidin-2-ones compounds are described. These thioxo-imidazolidine derivatives were prepared by alkylation and condensation with 4-fluoro-benzaldehyde or nucleophilic Michael addition with cyanoacrylates. The schistosomicidal activity of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one compounds was evaluated.
Assuntos
Imidazolidinas/síntese química , Imidazolidinas/farmacologia , Esquistossomicidas/síntese química , Esquistossomicidas/farmacologia , Animais , Cristalografia por Raios X , Feminino , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/toxicidadeRESUMO
The synthesis and physicochemical properties of 4-butyl-2H-benzo[1,4]thiazin-3-one derivatives are described. These new compounds were synthesised by alkylation in 4-N position and acylation and/or alkylation of 6-NH2 by phase transfer catalysis. Acid hydrolysis of 6-alkylacylamino group yielded 6-alkylamino-4-butyl-2H-benzo[1,4]thiazin-3-ones. The antimicrobial in vitro activity was determined on five compounds.
Assuntos
Anti-Infecciosos/síntese química , Tiazinas/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Tiazinas/farmacologiaRESUMO
Synthesis and physico-chemical properties of new 3-benzyl-4-thioxo-5-arylideneimidazolidine-2-ones and 3-benzyl-5-arylideneimidazolidine-2,4-dione are described. These compounds were synthesized by condensation reaction from aromatic aldehydes and 3-substituted imidazolidine-2,4-diones or 4-thioxoimidazolidine-2-ones. The N-alkylation of 5-benzylideneimidazolidine-2,4-dione led simultaneously to mono- and dialkylated derivatives. The nucleophilic addition of 1-methyl-3-benzylimidazolidine-2,4-dione with 2-cyano-3-(3,4-dichlorophenyl) acrylate also yielded the 3-substituted 5-arylideneimidazolidine-2,4-dione derivative. Antimicrobial in vitro activity was determined on some compounds.
Assuntos
Antibacterianos/síntese química , Imidazóis/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Contagem de Colônia Microbiana , Cromatografia Gasosa-Espectrometria de Massas , Imidazóis/química , Imidazóis/farmacologiaRESUMO
To complete a preceding work, we have made a QSAR study of a series of mono- or bi-pyridines, aminoxidized or not, wearing diverse substituents and related to the mushroom toxin orellanine. For the description of these molecules, we tried several sterical parameters which we have recently defined (sigma D and sigma S) or which we define here (D3) as well as physical and quantal parameters calculated with the CNDO/2 method, besides the parameter of hydrophobicity log P. Among the regression equations obtained, three have a correlation coefficient greater than 0.96, which is very high, taking into account the nature of the biological response (LD50). The importance of the hydrophobicity and of the size of the molecules in the expression of their toxicity is confirmed, as well as the particularity of orellanine in the series studied.
Assuntos
2,2'-Dipiridil/análogos & derivados , Piridinas/toxicidade , 2,2'-Dipiridil/toxicidade , Animais , Dose Letal Mediana , Camundongos , Conformação Molecular , Análise de Regressão , Relação Estrutura-AtividadeRESUMO
The synthesis of five chlorobenzyl benzylidene imidazolidinediones and four fluorobenzyl benzylidene thiazolidinediones is described. In order to investigate their antimicrobial activity they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus, Mycobacterium smegmatis and Escherichia coli.
Assuntos
Anti-Infecciosos/síntese química , Compostos de Benzilideno/síntese química , Imidazóis/síntese química , Tiazóis/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Compostos de Benzil/síntese química , Compostos de Benzil/farmacologia , Compostos de Benzilideno/farmacologia , Fungos/efeitos dos fármacos , Imidazóis/farmacologia , Testes de Sensibilidade Microbiana , Tiazóis/farmacologiaRESUMO
The synthesis of six benzylidene thiazolidinediones and four benzylidene imidazolidinediones is described. In order to investigate their antifungal activity, they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus and Escherichia coli.
Assuntos
Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Neurospora crassa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/farmacologia , Técnicas In VitroRESUMO
The synthesis and physico-chemical properties of fourteen 4-thio-5-arylidene-thiazolidine-2-ones and eight 3-(4-bromophenacyl)-4-thio-5-arylidene-thiazolidine-2-ones are described. These products were synthetized by the aldolisation-crotonisation reaction between aromatic aldehydes and 4-thio-thiazolidine-2-one followed by N-alkylation of this substituted compounds.
Assuntos
Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologiaRESUMO
Quantitative structure-activity relationships are described for twenty six title compounds. Five compounds exhibit a significant hypoglycemic activity like insulin used as standard. The aim of the present paper is to investigate the contribution of the different substituents in the biological activity. The application of Fujita-Ban and Hansch models has shown that lipophilic and electronic parameters seem to be the best explanation of variance of biological data.
Assuntos
Hipoglicemia/induzido quimicamente , Imidazóis/farmacologia , Tiazóis/farmacologia , Animais , Feminino , Masculino , Camundongos , Relação Estrutura-AtividadeRESUMO
Synthesis and physico-chemical properties of 3-(4-bromobenzyl)-, 3-(4-chlorobenzyl)-5-arylidene-thiazolidine-2,4-diones and 3-(4-chlorobenzyl)-4-thioxo-5-arylidene-thiazolidin-2- ones are described. Twelve new products were synthesized by the aldolisation-crotonisation reaction from aromatic aldehydes and N-alkylated thiazolidinediones or thioxothiazolidinones. Seven compounds were preliminary tested for their bacteriostatic activity.
Assuntos
Antibacterianos/síntese química , Tiazóis/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tiazóis/farmacologiaRESUMO
The synthesis and the physico-chemical properties of four 3-(4-bromophenacyl)-5-arylidene-thiazolidine-2,4-diones, two 3-(4-bromobenzyl)-5-arylidene-thiazolidine-2,4-diones and seven 3-(4-chlorobenzyl)-5-arylidene-4-thio-imidazolidine-2-ones were described. These products were synthetized by the aldolisation-crotonisation reaction between aromatic aldehydes and substituted thiazolidinediones or thio-imidazolidinones.
Assuntos
Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Imidazóis/química , Imidazóis/síntese química , Imidazolidinas , Tiazóis/química , Tiazóis/síntese química , Tiazolidinedionas , Edema Encefálico/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Imidazóis/farmacologia , Tiazóis/farmacologiaRESUMO
Synthesis and physico-chemical properties of five bromobenzyl-benzylidene-imidazolidinediones and five nitrobenzyl- or benzyl-benzylidene-thiazolidinediones are described. The microbiological activity of bromobenzyl-benzylidene-imidazolidinediones against microorganisms such as Candida albicans, Neurospora crassa and Mycobacterium smegmatis are evaluated.
Assuntos
Anti-Infecciosos/síntese química , Compostos de Benzilideno/síntese química , Etilenotioureia/síntese química , Tiazóis/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Compostos de Benzil/síntese química , Compostos de Benzil/farmacologia , Compostos de Benzilideno/farmacologia , Candida albicans/efeitos dos fármacos , Etilenotioureia/farmacologia , Mycobacterium/efeitos dos fármacos , Neurospora crassa/efeitos dos fármacos , Tiazóis/farmacologiaRESUMO
The antifungal activity against Neurospora crassa of some 5-benzilidene pyrrolone and furanone derivatives was realised. Relations between the structure and this biological activity are established with Fujita-Ban and Hansch methods. The preponderant part of lipophilicity, resonance effect and E or Z configurations have been showed.
Assuntos
Antifúngicos/farmacologia , Compostos de Benzilideno/farmacologia , Furanos/farmacologia , Neurospora crassa/efeitos dos fármacos , Pirróis/farmacologia , Fenômenos Químicos , Química , Relação Estrutura-AtividadeRESUMO
Synthesis and physico-chemical properties of four 3-benzyl or 3-(4-chlorobenzyl)-4-thioxo-5-arylazo-imidazolidin-2-ones, five 3-(4-nitrobenzyl)-5-arylidenethiazolidine-2,4-diones and three 3-(4-phenyl-phenacyl)-4-thioxo-5-arylidenethiazolidin-2-ones have been described. These new products were synthesized by an aldolisation-crotonisation reaction from aromatic aldehydes and 3-substituted thioxothiazolidin-2-ones or thiazolidine-2,4-diones. The arylazo-imidazolidine compounds were synthesized by copulation of diazonium ions with imidazolidines. Antimicrobial activity was determined for some compounds.
Assuntos
Anti-Infecciosos/síntese química , Antifúngicos/síntese química , Tiazóis/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Tiazóis/química , Tiazóis/farmacologiaRESUMO
Synthesis and physico-chemical properties of some 3-benzyl- and 3-phenacyl-4-thioxo-5-benzylidenethiazolidin-2-one derivatives are described. Fifteen new compounds were synthesized from thiazolidin-2-one by thionation of the 4-carbonyle, alkylation of the 3-N and aldolisation-crotonisation of 5-CH(2) with aromatic aldehydes. Soon, these new compounds will be tested for their bacteriostatic activity.
Assuntos
Anti-Infecciosos/síntese química , Tiazóis/síntese química , Tiazóis/farmacologia , Alquilação , Anti-Infecciosos/farmacologia , Indicadores e ReagentesRESUMO
The synthesis of six benzylidene thiazolidine-diones and three benzylidene imidazolidine-diones is described. In order to investigate their antimicrobial activity, they are evaluated against micro-organism such as Staphylococcus aureus, Streptococcus feacalis, Mycobacterium smegmatis and Neurospora crassa.
Assuntos
Anti-Infecciosos/síntese química , Compostos de Benzilideno/síntese química , Hidantoínas/síntese química , Tiazóis/síntese química , Antibacterianos , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Compostos de Benzilideno/farmacologia , Fungos/efeitos dos fármacos , Hidantoínas/farmacologia , Testes de Sensibilidade Microbiana , Tiazóis/farmacologiaRESUMO
Synthesis and physico-chemical properties of nine 3-(4-fluoro or chlorobenzyl)-5-arylidène-imidazolidine-2,4-diones, four 3-(4-fluoro or bromobenzyl)-5-arylidène-thiazolidine-2,4-diones and three 3-)4-bromophénacyl)-5-arylidène-thiazolidine-2,4- diones has been described. These compounds were synthesized by aldolisation-crotonisation reaction from aromatic aldehydes and 3-substituted imidazolidine-2,4-diones or thiazolidine-2,4-diones. In vitro cytotoxic activity was determined for compounds 8, 17, 18, 21 and 22.
Assuntos
Antineoplásicos/síntese química , Imidazóis/síntese química , Tiazóis/síntese química , Antineoplásicos/farmacologia , Humanos , Imidazóis/farmacologia , Células KB , Tiazóis/farmacologiaRESUMO
A new set of derivative thioxothiazolidinones and thioxoimidazolidinones 3,5-dissubstituted has been synthesized with satisfactory yield from the condensation Knoevenagel type between benzaldéhydes and 4-thioxothiazolidin-2-one, 2-thioxothiazolidin-4-one and 1-méthyl-2-thioxoimidazolidin-4-one compounds following by N-alkylation with aryl or acyl halides. The physico-chemical properties of the 5-benzylidene-3-[2-(4-chlorophenyl)-2-oxoethyl]-2 (or 4)-thioxothiazolidin-4 (or 2)-ones and 5-benzylidene-1-methyl-2-thioxoimidazolidin-4-ones synthesized have been described.
Assuntos
Imidazóis/química , Tiazóis/química , Tionas/química , Alquilação , Fenômenos Químicos , Físico-Química , Imidazóis/síntese química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Tiazóis/síntese química , Tionas/síntese químicaRESUMO
Synthesis and physico-chemical properties of six 5-arylidène-3-benzyl-1-methyl-2-thioxoimidazolidin-4-ones and three 2-arylidene-6-nitro-2H-1,4-benzothiazin-3(4H)-ones have been described. These new compounds were synthetised by Knoevenagel condensation reaction from aromatic aldehydes. The N-alkylation reaction of arylidenebenzothiazines by methyl iodide give the N-methylarylidenebenzothiazines.