Synthesis of some novel analogues of 4-[l-pyrrolidinyl] piperidine and their effect on plasma glucose level

In the present study some compounds of 4-[1-Pyrrolidinyl] Piperidine [I] have been synthesized. Structures of compounds were confirmed by using HNMR, IR, Mass and UV spectrophotometer techniques. All the derivatives [II, III, IV and V] and the parent compound [I] at the dose of 100 mg/kg were evaluated for their effect on plasma glucose level. Compound [II] was the only derivative which showed effect on plasma glucose level

Febrifugine derivative antimalarial activity: quantum mechanical predictors / Descritores da atividade antimalarial de derivados de febrifugina obtidos via mecânica qüântica

Plasmodium falciparum resistant strain development has encouraged the search for new antimalarial drugs. Febrifugine is a natural substance with high activity against P. falciparum presenting strong emetic property and liver toxicity, which prevent it from being used as a clinical drug. The search for analogues that could have a better clinical performance is a current topic. We aim to investigate the theoretical electronic structure by means of febrifugine derivative family semi-empirical molecular orbital calculations, seeking the electronic indexes that could help the design of new efficient derivatives. The theoretical results show there is a clustering in well-defined ranges of several electronic indexes of the most selective molecules. The model proposed for achieving high selectivity was tested with success.

O desenvolvimento de linhagens resistentes de Plasmodium falciparum tem encorajado a busca por novas drogas antimalariais. A febrifugina é uma substância natural com alta atividade contra o P. falciparum que apresenta propriedade emética e toxicidade para o fígado tal que não permitem o seu uso clínico. A busca por análogos que possam ter uma performance clínica melhor é um tema de pesquisa atual. Nosso objetivo é investigar a estrutura eletrônica teórica de uma família de derivados da febrifugina empregando cálculos semi-empíricos de orbitais moleculares, procurando por índices eletrônicos que possam ajudar a modelar novos derivados mais eficientes. Os resultados teóricos mostram que para as moléculas mais seletivas existe um agrupamento dos valores de determinados índices em intervalos bem definidos. O modelo proposto para se obter alta seletividade foi testado com sucesso.

Enhancement of dissolution properties of repaglinide using liquisolid compacts

The potential of liquisolid systems to improve the dissolution properties of water insoluble drugs was investigated using repaglinide as the model medication. The new formulation technique of liquisolid compacts was used to convert liquid medications such as solution or suspension of repaglinide in polysorbate 80, a non-volatile liquid vehicle, into acceptably flowing and compressible powders by blending with selective powder excipients. Several liquisolid tablet formulations were prepared using a new mathematical model to calculate the appropriate quantities of powder and liquid ingredients required to produce acceptably flowing and compressible admixtures. Due to their increased wetting properties and surface of drug available for dissolution. liquisolid compacts demonstrated significantly higher drug release rate than that of commercial products. Differential thermal analysis [DTA] was used for evaluation of physicochemical properties of repaglinide in liquisolid formula. It was shown that Avicel PH101 had more liquid retention potential in comparison with starch, and the formulations containing polysorbate 80 as a liquid medication, Avicel PH101 as a carrier and calcium silicate as a coat. showed higher dissolution rate at excipients ratio 5

Antineoplastons: major players in the biochemical defensive system against cancer

Antineoplastons are naturally occurring peptides and amino acid derivatives that were originally isolated from human urine. They possess a broad-spectrum antitumor activity and seem to be much safer and specific than many of the available chemotherapeutic agents. Their selectivity is likely entailed to preferential interaction with cellular components or signaling mechanisms that predominate in cancer cells. Our studies on breast cancer- cell lines and -patients indicated the efficacy of antineoplaston-A10 and its derivatives as antimitotic, immunemodulator and cytodifferentiating agents. Moreover, phase-I and phase-II clinical trials implied the utility of antineoplastons in treating neoplasms of various origins. Combination with lower doses of known chemotherapeutic agents or in conjunction with radiotherapy was a promising therapeutic strategy. Such regimens were likewise effective in cases with recurrent or drug-resistant neoplasms. Intensive research is continuing to reveal more on antineoplastons and their biologic characteristics

Molecular mechanics calculations of opioid ligands of the 4-arylpiperidine class.

Molecular mechanics calculations have been carried out on N-methyl-4-phenyl-4-piperidinols substituted at 2,3-, 2,5- and 2,6-positions with methyl groups. Besides the alcohols, their esters and methiodides were also studied. The molecular mechanics conformations have been compared with conformations determined experimentally by NMR or X-ray diffraction.

Kinetics of the reactions of methyl-2,3-dibromo-3- [4-substituted phenyl] propanoates with piperidine IV

The rates of elimination of a series of erythromethyl- 2,3-dibromo-3-[4-substituted phenyl] propanoates [1 alpha-d] have been determined conductimetrically in methanol using piperidine as a base. The elimination reactions gave exclusively Z-methyl-2-bromo-3- [4-substituted phenyl] propanoates [2 alpha-d]. The specific rate constants of the reactions gave a good Hammett correlation with p values of 0.39-1.31 which suggest a carbonionic transition state. The results suggested that the reaction proceeds by initial isomerization of the erythro-dibromo-compound to the threo-isomer, which spontaneously eliminates HBr to give [2 alpha-d]

Substitution and elimination reactions Reaction of methyl 2,3 -dibromo-3- [P-substituted phenyl] propanoates with piperidine

The reaction of erythro-methyl 2,3-dibromo-3-[p-substituted phenyl] propanoates 1a-d with 4 molar equivalent of piperidine in methanol gave a mixture of erythro and threo-methyl 2,3-bis-piperidino-3-[p- substituted phenyl] propanoates 2a-d. The identification of the configuration of the products 2a-d was based on 1H-NMR spectra. The mechanism of the reaction is discussed