ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Chemistry, Pharmaceutical/methods , Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors , Norepinephrine/antagonists & inhibitors , Propanolamines/chemical synthesis , Selective Serotonin Reuptake Inhibitors/chemical synthesis , Adrenergic Uptake Inhibitors/pharmacology , Animals , Dogs , Dopamine Plasma Membrane Transport Proteins/chemistry , Drug Design , Humans , Inhibitory Concentration 50 , Ligands , Models, Chemical , Propanolamines/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Carboxylic Acids/chemistry , Carboxylic Acids/metabolism , DNA-Binding Proteins/agonists , Quinolines/chemistry , Quinolines/metabolism , Receptors, Cytoplasmic and Nuclear/agonists , Animals , Carboxylic Acids/pharmacology , Crystallography, X-Ray , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , Gene Expression , Humans , Ligands , Liver X Receptors , Macrophages/drug effects , Macrophages/metabolism , Mice , Models, Molecular , Orphan Nuclear Receptors , Quinolines/pharmacology , Receptors, Cytoplasmic and Nuclear/chemistry , Receptors, Cytoplasmic and Nuclear/metabolism , Substrate Specificity , Transcriptional ActivationABSTRACT
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]
