RESUMEN
Terminal alkynes, secondary amines, and aldehydes undergo "solid-phase Mannich condensation". A set of diverse aldehyde inputs was examined. Aliphatic, aralkyl, aryl, and heteroaryl carboxaldehydes give good yields of Mannich adduct of high purity. Benzaldehydes containing electron-donating substituents that decrease the electrophilicity of the carbonyl center, or heteroaryl aldehydes that are similarly deactivated by resonance effects, do not undergo reaction.
Asunto(s)
Aldehídos/química , Aldehídos/síntesis química , Alquinos/síntesis química , Aminas/síntesis química , Benzaldehídos/síntesis química , Benzaldehídos/química , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Bases de Mannich/química , Espectrometría de MasasRESUMEN
Alpha-(3-Pyridylmethyl)-beta-aminotetralins were acylated with amino-piperidinyl and-pyrrolidinyl acetic acids, and with (aminomethyl)cyclohexanecarboxylic acid. Reaction with acyl chlorides, chloroformates, and isocyanates gave amides 8e, carbamates 9, and ureas 10, which bound to the Y5 receptor with nanomolar affinity. Congeners 11a and 11d containing a terminal benzimidazolone group were shown to be functional Y5 antagonists.
Asunto(s)
2-Naftilamina/análogos & derivados , Piridinas/química , Piridinas/farmacología , Receptores de Neuropéptido Y/antagonistas & inhibidores , 2-Naftilamina/química , 2-Naftilamina/farmacología , Acilación , HumanosRESUMEN
[3a,4,5,9b-Tetrahydro-1H-benzo[e]indol-2-yl]amines were prepared via reductive amination and concomitant cyclization of alpha-cyanomethyl-beta-aminotetralins. N-acylation with omega-sulfonamido-carboxylic acids and subsequent reduction afforded a series of N-(sulfonamido)alkyl[tetrahydro-1H-benzo[e]indol-2-yl]amines, which bound to the human neuropeptide Y Y5 receptor with nanomolar affinity.
Asunto(s)
Indoles/farmacología , Receptores de Neuropéptido Y/antagonistas & inhibidores , Cristalografía por Rayos X , Humanos , Indoles/síntesis química , Indoles/química , Estructura MolecularAsunto(s)
Receptores de Neuropéptido Y/antagonistas & inhibidores , Sulfonamidas/síntesis química , Tetrahidronaftalenos/síntesis química , Línea Celular , Humanos , Ensayo de Unión Radioligante , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacología , Tetrahidronaftalenos/química , Tetrahidronaftalenos/metabolismo , TransfecciónRESUMEN
Solid-phase organic synthesis, particularly when used in conjunction with combinatorial techniques, is emerging as a revolutionary technology in chemistry. Multi-component reaction systems are particularly valued because several elements of diversity can be introduced in a single transformation thereby expanding the diversity of compound libraries. A variety of multi-component reactions have been successfully adapted for solid-phase technology as described in this review.
