In the backbone atoms as in comparison with the crystal structure of both complexes.Results and discussionChemistryIn our continued interest [30, 377] in the development of very expedient approaches for the synthesis of diverse heterocyclic compounds of biological significance by means of one-pot multi-component reactions (MCRs) and avoiding organic solvents throughout the reactions in organic synthesis results in efficient, environmentally benign reagents, clean, and economical technologies (Green Chemistry Concepts). Inside the present investigation, reaction of equimolar amounts of barbituric acid 1a,b dimedone 2 with aldehyde three in presence of aqueous diethylamine medium at RT afforded zwitterionic adducts 4a and 5a in quantitative yields by very simple filtration (Scheme 1).Biological activityThirty-two new derivatives of barbituric acid as zwitterionic adducts of diethyl ammonium salts obtaining bis(6-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,three,4tetrahydropyrimidin-5-yl) (4a ), bis-(6-hydroxypyrimidine-2,4(1H,3H)-dione) (4il), (2-hydroxy-4,4dimethyl-6-oxocyclohex-1-en-1-yl)-1,3-dimethyl2 , six – d i oxo – 1 , 2 , 3 , six – t e t r a hy d r o p y r i m i d i n – 4 – o l at e (4mz), 4-((6-Hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4tetrahydropyrimidin-5-yl)(6-hydroxy-2,4-dioxo-1,two,three,4tetrahydropyrimidin-5-yl)methyl) benzaldehyde (5l), (2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl) methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate (5mr) and twelve derivatives of dimedone aszwitterionic adducts of diethyl ammonium salts having bis-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en (5a and 5s) as simple nucleus had been screened in vitro for their ureas enzyme inhibition potential against thiourea (IC50 = 21.287944-16-5 custom synthesis 2 1.2-Bromo-4-formylnicotinonitrile Chemscene three ), as an standard tested compounds (Table 1). Among barbituric acid zwitterionic adducts (4a ) obtaining bis(6-Hydroxy-1,3-dimethyl-2,4-dioxo-1,2,three,4tetrahydropyrimidin-5-yl) ring as simple nucleus, all ccompounds 4a, 4b, 4d, 4e, 4g and 4f showed IC50 values 39.3 0.36, 34.four 1.57, 31.six 0.79, 27.five 0.PMID:23800738 12, 28.5 0.41, and 40.three 0.32 respectively, and were located to be the potent urease inhibitors except compounds 4c (IC50 = 54.2 0.47 ) and 4f (IC50 = 54.two 0.83 ), whilst compared together with the common compound thiourea (IC50 = 21.two 1.three ). Among the barbituric acid derived derivatives (4il), obtaining bis(6-hydroxypyrimidine-2,4(1H,3H)dione) as backbone, all tested compounds i.e. 4i (IC50 = 17.6 0.23 ), 4j (IC50 = 22.3 0.73 ), four k (IC50 = 25.eight 0.23 ) and 4 l (IC50 = 22.7 0.20 ) were identified to be potent inhibitors of urease enzyme. Methyl substituted phenyl ring containing compound 4i (IC50 = 17.6 0.23 ) was probably the most active candidate of your series. Third series from the derivatives of barbituric acids obtaining (2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)1,3-dimethyl-2,6-dioxo-1,2,three,6-tetrahydropyrimidin4-olate ring as fundamental nucleus (4mz) had been also evaluated for their urease enzyme inhibition. Compounds 4m (IC50 = 39.3 0.79 ), 4n (IC50 = 41.2 0.58 ), 4p (IC50 = 39.7 0.70 ), 4q (IC50 = 24.6 0.42 ), 4r (IC50 = 27.5 0.19 ), 4x (IC50 = 38.five 0.28 ), and 4z (IC50 = 39.8 1.38 ) was discovered to be potent urease inhibitors against the regular thiourea. Amongst fourth series of your derivatives of barbituric acid obtaining (2-hydroxy-4,4-dimethyl-6-oxocyclohex1-en-1-yl)methyl-2,6-dioxo-1,two,three,6-tetrahydropyrimidin4-olate) ring as fundamental nucleus (5mr), compound 5n (IC50 = 23.7 0.57 ), 5o (IC50 = 34.6 0.79 ), 5p (IC50 = 27.four 0.54 ), and 5q (IC50 = 41.6 0.41 ), showed poetnt urease inhibiton.
