RESUMEN
The phase-transfer catalytic alkylation of N,N-dialkylmalonamic tert-butyl esters in the presence of 1 mol% of (S,S)-3,4,5-trifluorophenyl-NAS bromide afforded highly enantioselective (S)-mono-alpha-alkylated products (up to 96% ee), which could be readily converted into versatile chiral building blocks without loss of chirality.
Asunto(s)
Ésteres/química , Malonatos/química , Alquilación , Catálisis , Estereoisomerismo , Especificidad por SustratoAsunto(s)
Chalconas/química , Alcaloides de Cinchona/química , Compuestos Epoxi/síntesis química , Tensoactivos/química , Catálisis , Chalcona/análogos & derivados , Chalcona/síntesis química , Chalcona/química , Compuestos Epoxi/química , Hexosas/química , Modelos Moleculares , Estructura Molecular , Octoxinol/química , Poloxaleno/química , Polietilenglicoles/química , Polisorbatos/química , EstereoisomerismoRESUMEN
A new Merrifield-resin-derived glycinimine tert-butyl ester (9) was prepared and applied to the enantioselective synthesis of non-natural alpha-amino acids. High enantioselectivities (86 to >99% ee) were accomplished by employing the aldimine linker under phase-transfer alkylation conditions, using 50% aqueous CsOH in toluene/chloroform (7:3) at 0 degrees C in the presence of N-(9-anthracenylmethyl)-O(9)-allylcinchonidium bromide (10 mol %).
Asunto(s)
Aminoácidos/síntesis química , Reactivos de Enlaces Cruzados/química , Iminas/química , Alquilación , Catálisis , Conformación Molecular , EstereoisomerismoRESUMEN
Seventeen biarylcarboxybenzamide derivatives were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor (VR1) in rat DRG neurons. The replacement of the piperazine moiety of the lead compound 1 with phenyl ring showed quite enhanced antagonistic activity. Among the prepared derivatives, N-(4-tert-butylphenyl)-4-pyridine-2-yl-benzamide (2, IC(50)=31 nM) and N-(4-tert-butylphenyl)-4-(3-methylpyridine-2-yl)benzamide (3g, IC(50)=31 nM), showed 5-fold higher antagonistic activity than 1 in (45)Ca(2+)-influx assay.
Asunto(s)
Benzamidas/síntesis química , Benzamidas/farmacología , Canales Iónicos/antagonistas & inhibidores , Animales , Señalización del Calcio/efectos de los fármacos , Ganglios Espinales/citología , Concentración 50 Inhibidora , Canales Iónicos/agonistas , Ligandos , Neuronas , Ratas , Receptores de Droga/antagonistas & inhibidores , Relación Estructura-Actividad , Canales Catiónicos TRPVRESUMEN
Four pyrrolidine derivatives were prepared by the formation of a 5-membered ring based on capsazepine. Among them, the two carbon extended derivatives, 4a (IC(50)=55 microM) and 4b (IC(50)=3 microM), both showed different levels of antagonist activity against the vanilloid receptor in a (45)Ca(2+)-influx assay.
Asunto(s)
Capsaicina/análogos & derivados , Pirrolidinas/síntesis química , Pirrolidinas/farmacología , Receptores de Droga/antagonistas & inhibidores , Tiourea/análogos & derivados , Animales , Animales Recién Nacidos , Calcio/metabolismo , Capsaicina/química , Cristalografía por Rayos X , Indicadores y Reactivos , Modelos Moleculares , Conformación Molecular , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/metabolismo , Ratas , Tiourea/síntesis química , Tiourea/farmacologíaRESUMEN
A series of N-4-substituted-benzyl-N'-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG neurons. Their structure-activity relationship reveals that not only the two oxygens and amide hydrogen of sulfonamido group, but also the optimal size of methyl in methanesulfonamido group play an integral role for the antagonistic activity on vanilloid receptor.
Asunto(s)
Capsaicina/metabolismo , Neuronas/efectos de los fármacos , Receptores de Droga/antagonistas & inhibidores , Sulfonamidas/farmacología , Tiourea/farmacología , Animales , Animales Recién Nacidos , Calcio/metabolismo , Células Cultivadas , Ganglios Espinales/efectos de los fármacos , Ligandos , Estructura Molecular , Ratas , Receptores de Droga/agonistas , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Tiourea/análogos & derivados , Tiourea/síntesis químicaRESUMEN
A series of N-4-methansulfonamidobenzyl-N'-2-substituted-4-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG neurons. Their structure-activity relationship reveals that there is a space for another hydrophobic binding interaction around 2-position in 4-tert-butylbenzyl region. Among the prepared derivatives, 6n show the highest antagonistic activity against the vanilloid receptor (IC(50)=15 nM).
Asunto(s)
Receptores de Droga/antagonistas & inhibidores , Sulfonamidas/química , Tiourea/química , Animales , Células Cultivadas , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Ligandos , Ratas , Receptores de Droga/metabolismo , Sulfonamidas/metabolismo , Tiourea/metabolismoRESUMEN
Twenty-seven N,N',N"-trisubstituted thiourea derivatives were prepared. Among them, 1-[3-(4'-hydroxy-3'-methoxy-phenyl)-propyl]-1,3-diphenethyl-thiourea (8l, IC(50)=0.32 microM), showed 2-fold higher antagonistic activity than that of capsazepine (3, IC(50)=0.65 microM) against the vanilloid receptor in a (45)Ca(2+)-influx assay.