RESUMEN
Several new derivatives of adenine, purine, and theophylline containing the (CF3)2CH group connected to a nitrogen atom of the imidazole ring were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated products in 47-78% yield. While for purine and 4- and 5-azabenzimidazole, the reaction led to a mixture of two isomers, the reaction of adenine and the corresponding 2-fluoro derivative was regioselective, resulting in the formation of only one isomer in each case. The alkylation of theophylline led to the formation of a new derivative of caffeine.
RESUMEN
A simple and general procedure for the preparation of Diels-Alder adducts of perfluorinated thioketones and various dienes is reported. The corresponding Diels-Alder adducts were prepared in 30-78% yield under mild conditions via a reaction of a mixture of fluoroolefins, sulfur, diene and CsF as a catalyst.
RESUMEN
The effectiveness of hetero-COSY, HETCOR, HMQC, and HSQC two-dimensional NMR pulse sequences for detection of (19)F-(1)H correlations by scalar coupling was evaluated on monofluorinated and polyfluorinated test compounds. All four of these sequences were effective in observing (1)H-(19)F correlations, using either (19) F or (1)H as the observe nucleus. All four sequences were amenable, to some degree, to adjustment to observe larger or smaller couplings preferentially. A 1/2J echo filter was effectively applied to remove artifacts from (2)JFF strong coupling. The HETCOR experiments afforded the best overall combination of sensitivity, resolution and selectivity for JHF.
RESUMEN
A series of 3-(arylamino)-3-phenylpropan-2-olamines was prepared and screened for their ability to inhibit monoamine reuptake. A number of analogues displayed significant dual norepinephrine and serotonin reuptake inhibition. Compounds in this class exhibited minimal affinity for the dopamine transporter.
Asunto(s)
Química Farmacéutica/métodos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/antagonistas & inhibidores , Norepinefrina/antagonistas & inhibidores , Propanolaminas/síntesis química , Inhibidores Selectivos de la Recaptación de Serotonina/síntesis química , Inhibidores de Captación Adrenérgica/farmacología , Animales , Perros , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/química , Diseño de Fármacos , Humanos , Concentración 50 Inhibidora , Ligandos , Modelos Químicos , Propanolaminas/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Relación Estructura-ActividadRESUMEN
A series of potent and binding selective LXRbeta agonists was developed using the previously reported non-selective LXR ligand WAY-254011 as a structural template. With the aid of molecular modeling, it was found that 2,3-diMe-Ph, 2,5-diMe-Ph, and naphthalene substituted quinoline acetic acids (such as quinoline 33, 37, and 38) showed selectivity for LXRbeta over LXRalpha in binding assays.
Asunto(s)
Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Proteínas de Unión al ADN/agonistas , Quinolinas/química , Quinolinas/metabolismo , Receptores Citoplasmáticos y Nucleares/agonistas , Animales , Ácidos Carboxílicos/farmacología , Cristalografía por Rayos X , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Expresión Génica , Humanos , Ligandos , Receptores X del Hígado , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Modelos Moleculares , Receptores Nucleares Huérfanos , Quinolinas/farmacología , Receptores Citoplasmáticos y Nucleares/química , Receptores Citoplasmáticos y Nucleares/metabolismo , Especificidad por Sustrato , Activación TranscripcionalRESUMEN
The first efficient and regioselective palladium-catalyzed cyclization of internal alkynes and 2-amino-3-iodoacrylates to give moderate to excellent yields of highly functionalized pyrroles has been developed. This approach is applicable to a range of alkynes and affords the deacylated pyrrole under reaction conditions for most substrates. [reaction: see text]