A QSAR study on a series of N-methyl pyrimidones acting as HIV integrase inhibitors.

A quantitative structure-activity relationship (QSAR) study has been performed on integrase (IN) inhibition activity of a large series of N-methyl pyrimidones [Gardelli et al. (2007) J Med Chem 50, 4953-4975)] having varying heterocyclic ring substitution at 2-position of pyrimidone ring. The activity is found to be significantly correlated with surface tension and molar volume of the molecules. The whole series of compounds is divided into two subsets: a training set and a test set. A significant correlation is obtained for the training set, which is then used to predict the activity of compounds in the test set. The predicted activities of compounds in the test set are found to be very close to their observed activities. The predicting ability of the correlation obtained is judged by leave-one-out jackknife procedure. The correlation shows the effective role of the surface tension and molar volume of the molecules. From the correlation obtained, the integrase inhibition activities are predicted for some new prospective compounds.

Synthesis of thienopyrimidotriazines, a new fused heterocyclic ring system

Benzothieno [2, 3: 4', 5'] pyrimido [2, l-c] [1, 2, 4] triazines 2, 4 and 6 which represent a new fused heterocyclic ring system were synthesized by reacting 2-hydrazino-5, 6, 7, 8-tertrahydrobenzothieno [2, 3-d]-pyrimidin-4 [3H]-one [1] with phenacyl bromide, bromomalononitrile or chloroacetyl chloride, respectively. Condensation of 6 with aromatic aldehydes produced arylmethylene derivatives 7a, b. Reaction of 1 with phthalic anhydride afforded the phthalazine derivative 8. Also, compound 1 reacted with beta- diketones and with ethyl acetoacetate to produce the pyrazolyl 9a-c and pyrazolinone derivatives 11, respectively. Compound 11 condensed with aromatic aldehydes and coupled with diazotized aromatic amines to afford the corresponding arylmethylene and arylazo derivatives 12 and 13, respectively. All compounds were confirmed by IR, HNMR and analytical data

Potential anticancer drugs: synthesis of some fused arylhydrazonoindeno [1,2-d] thiazolo and thiazinopyrimidinones

4-aryl-1,2,3,4-tetrahydro-5-oxoindeno [1,2-d] pyrimidine-2-thiols [I] were synthesized in the laboratories and their corresponding hydrazono derivatives [II] were submitted to react with chloroacetic acid, 2-bromopropionic acid or 3-bromopropionic acid in the presence of fused sodium acetate and acetic anhydride to give 5-aryl-2,3- dihydro-5H, 6-arylhydrazonoindeno [1,2-d] thiazolo [3,2-a] pyrimidin-3-ones [III], its methyl derivatives [IV] and 6-aryl-6H, 7-arylhydrazonoindeno [1,2-d]-pyrimidino-[2,1-b]-1,3-thiazin-4-ones [V], respectively. The indenothiazolopyrimidones [III] condensed with aromatic aldehydes in the presence of acetic anhydride to yield 2-arylmethylene-5 aryl-2,3-dihydro-5H-6-arylhydrazonoimdeno [1,2-d] thiazolo [3,2-a] pyrimidin-3-ones [VI], which was obtained directly from their arylhydrazono derivatives [II] by the reaction of chloroacetic acid in the presence of the corresponding aromatic aldehyde and in refluxing acetic acid/acetic anhydride mixture

Synthesis of some novel benzimidazole derivatives as antimicrobial agents

Synthesis of 2-[p-[5-aryl-1-[H or phenyl]-delta2 pyrazolin-3-yl] anilino] benzimidazoles [4a, b], 2-[p-aryl-2-isoxazolin-3-yl] anilino] benzimidazole [5], 2-[p-[6-aryl-2-[oxo or thioxo]-1,2,5,6- tetrahydropyrimidin-4-yl] anilino] benzimidazoles [6a,b] and 2-[p- sulfamoylanilino] benzimidazoles [7a-g] were synthesized. The new compounds showed inhibitory effect against the growth of Gram +ve, Gram -ve bacteria, yeast and fungi

El desarrollo de nuevas drogas antipsicoticas / Development of new antipsychotic drugs

Se da por sentado que en la esquizofrenia, los efectos terapéuticos de los neurolépticos se basan en el bloqueo de los receptores de dopamina situados en el cerebro. Sin embargo, también se admite que los neurolépticos "clásicos" presentan algunos incovenientes importantes: su relativa falta de efectos sobre los síntomas negativos y su capacidad de inducción de síntomas extrapoiramidales (SEP). Experiencias clínicas llevadas a cabo con pipamperona mostraron que un antagonista combinado de serotinina 5-HT2 y dopamina D2 presentaba ventajas en el tratamiento de la esquizofrenia. Esto se hizo patente a través de los efectos antiautísticos observados, de la regulación de los ritmos de sueño y de vigilia perturbados y de la baja tendencia a la inducción de SEP. Los estudios realizados con setoperona, compuesto de perfil farmacológico comparable, confirmaron estas observaciones. No se pudo explorar la exacta implicación del antagnista 5-HT2 en los tratamientos psicofarmacológicos de la esquizofrenia hasta no haberse realizado la síntesis del receptor antagonista selectivo y específico: la ritanserina. En efecto las pruebas de doble ciego efectuadas demostraron una majoría sensible de los síntomas negativos y extrapiramidales. Puesto que las ventajas de la monoterapia en el tratamiento de la esquizofrenia son innegables, lo lógico era pasar a la selección de un compuesto con un antagonismo central comparable al de...