Synthesis Of Barbiturates Research Articles

Design and Synthesis of Barbiturates and Hydantoins with Multitarget Antidiabetic Effect☆

☆ Taking in part of the Master in Pharmacy thesis of S. Juárez-Cruz Abstract. In current work, we prepared a series of ten 4-aryloxy-5-benzylidenebarbiturates and hydantoins as 1,3-thiazolidine-2,4-dione bioisosteres. An in silico pharmacological consensus analysis (PHACA) was conducted to assess the pharmacokinetic, pharmacodynamics, biopharmaceutical, and toxicological properties of compounds 1-10. The goal was to identify computationally safe hits using a color-coded system resembling a traffic light. The compounds identified as safe computational hits through PHACA were 1, 2, and 4 from the barbiturate series, which were then selected by in vitro assays targeting PPAR-γ, GPR40, and GLUT-4 gene expression. Additionally, these three compounds underwent in vivo evaluation through a glucose tolerance curve assay conducted on normoglycemic mice. Compounds 1 and 4 exhibited antihyperglycemic effects within the first thirty minutes post-administration. Molecular docking studies were conducted to clarify the dual effect and binding mode of compounds 1, 2 and 4 on PPAR-γ and GPR40. Compounds 1 and 4 exhibited robust in vitro and in vivo efficacy and could be considered as multitarget modulators with antidiabetic effect. Resumen. En este trabajo se preparó una serie de diez 4-ariloxi-5-bencilidenobarbituratos e hidantoínas como bioisósteros de la 1,3-tiazolidina-2,4-diona. Se realizó un análisis de consenso farmacológico in silico (PHACA) para evaluar las propiedades farmacocinéticas, farmacodinámicas, biofarmacéuticas y toxicológicas de los compuestos 1-10. El objetivo era identificar hits computacionales seguros utilizando un sistema codificado por colores que se asemeja a un semáforo. Los compuestos identificados como hits computacionales seguros fueron 1, 2 y 4 de la serie de barbituratos, que se eligieron para ensayos in vitro dirigidos a la expresión génica de PPAR-γ, GPR40 y GLUT-4. Además, estos tres compuestos se sometieron a una evaluación in vivo mediante un ensayo de curva de tolerancia a la glucosa realizado en ratones normoglucémicos. Los compuestos 1 y 4 exhibieron efectos antihiperglucémicos dentro de los primeros treinta minutos posteriores a la administración. Se realizaron estudios de acoplamiento molecular para clarificar el efecto dual y el modo de unión de los compuestos 1, 2 y 4 en PPAR-γ y GPR40. Los compuestos 1 y 4 exhibieron una sólida eficacia in vitro e in vivo, por lo que pueden considerarse moduladores polifarmacológicos con efecto antidiabético.

Novel Synthesis of Barbiturates.

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Novel Synthesis of Barbiturates

AbstractKnovenagel reaction of barbituric acid with different aldehydes were used to synthesize new barbiturates.This is a novel method which can be used to synthsis various types of new generation of barbiturates which are different from the previously reported.

One‐Pot Synthesis of Barbiturates on Reaction of Barbituric Acid with Aldehydes under Microwave Irradiation Using a Variety of Catalysts.

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Clinical studies of a new barbiturate (nealbarbitone).

Brandström (1957) in Sweden, has recently resolved certain problems in the synthesis of barbiturates with a neopentyl group as one of the ring substituents and the resulting compound 5-allyl-5-neopentyl-barbituric acid∗ has been subjected to experimental studies which show it to be less hypnotic and anaesthetic than amylobarbitone or pentobarbitone sodium and yet protective to rats subjected to a stress situation after the technique of Jacobsen and Sonné (1955). The drug is rapidly absorbed after oral administration, and has a duration of action between that of amylobarbitone and phenobarbitone.