Preclinical Studies With 5‐(3,4‐dichlorophenyl)‐5‐ethyl‐hexahydropyrimidine‐2,4,6‐trione

DeLong, Donald C.; Doran, Wilbur J.; Baker, Linville A.; Nelson, Janet D.

doi:10.1111/j.1749-6632.1970.tb53439.x

Cited by 5 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The space available for phenyl ring modification is limited, however, because the p - tert -butylphenyl analogue 1c is less potent, as is 5-(1-naphthyl) analogue 1d . A significant activity of meta - and para -halogen substituted derivatives of mephobarbital ( 1e – 1h ) , further suggested that attachment of a TFD residue at these positions should be a plausible approach. Finally, we viewed modifications of the phenyl ring with a TFD residue at the meta - and para -positions ( 1i ) more suitable than that at the ortho -position, as they would eliminate potential intramolecular reactions of a photogenerated carbene intermediate with nucleophilic groups of the barbiturate framework.…”

Section: Resultsmentioning

confidence: 99%

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

et al. 2012

View full text Add to dashboard Cite

We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by x-ray crystallography. Additionally, we obtained the 3H-labeled ligand with high specific radioactivity. R-(−)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC50 approaches those for propofol and etomidate, whereas S-(+)-14 is tenfold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(−)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human α1β2/3γ2L GABAA receptors. Finally, R-(−)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both α1 and β3 subunits of human α1β3 GABAA receptors. These results indicate R-(−)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

show abstract

Section: Resultsmentioning

confidence: 99%

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The therapeutic index for both of these is exceptionally high, about 100, and several additional analogues were almost as active [31]. It is of interest that 6thioguanine is very effective in combination antitumour therapy with araC [32-341. A remarkable example of a pyrimidine analogue with antiviral activity is 5-(3,4-dichlorophenyl)-5-ethyl-hexahydropyrimidine-2,4,6-trione [35] . This is more easily recognized as a barbital derivative, 5-ethyl-5'-(3,4-dichlorphenyl)barbital.…”

Section: Purine and Pyrimidine Derivativesmentioning

confidence: 99%

Progress with antiviral agents

Shugar

1974

FEBS Letters

View full text Add to dashboard Cite

“…27 Based on the direct alkylation of adenine, the method has been used to synthesize over 20 different 3-substituted adenines (3) with the purpose of testing their potential enzyme inhibition and antiviral activity. 28 Chemistry. Treatment of adenine with A2-isopentenyl bromide (7,y-dimethylallyl bromide) in dimethylacetamide for 30 h at room temperature furnished, after basification, 3-( 2-isopentenyl) adenine (3a) in 66% yield, thus constituting the most direct synthesis of triacanthine.7 *The preferential 3 substitution on adenine was accompanied by formation of the corresponding 9-and 1-substituted adenines 4 and 5 in about 14 and 8% yield, respectively, 4 5 paralleling the experience of Pal4 **in ethylation and methylation under somewhat different conditions.…”

mentioning

confidence: 99%

3-Substituted adenines. In vitro enzyme inhibition and antiviral activity

Fujii¹,

Walker²,

Leonard³

et al. 1979

J. Med. Chem.

Self Cite

View full text Add to dashboard Cite

The direct alkylation of adenine at the 3 position has been extended to produce series of 3-alkyl-, 3-allyl-, and 3-(substituted benzyl)adenines. When these compounds were tested for enzyme inhibition and antiviral activity in vitro, 3-n-pentyladenine was found to be the most active compound in inhibiting the enzyme dopamine-beta-hydroxylase, and 3-(2-bromobenzyl)adenine showed the most striking inhibition of multiplication of Vaccinia virus and of Herpes simplex virus in tissue culture.

show abstract

Preclinical Studies With 5‐(3,4‐dichlorophenyl)‐5‐ethyl‐hexahydropyrimidine‐2,4,6‐trione

Cited by 5 publications

References 8 publications

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

Progress with antiviral agents

3-Substituted adenines. In vitro enzyme inhibition and antiviral activity

Contact Info

Product

Resources

About