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Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H) and their docking and urease inhibitory activity.

Ziarani GM, Faramarzi S, Asadi S, Badiei A, Bazl R, Amanlou M - Daru (2013)

Bottom Line: The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate.Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity.Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chemistry, Alzahra University, Vanak Square, P,O, Box 19938939973, Tehran, Iran. gmziarani@hotmail.com.

ABSTRACT

Background: A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.

Results: Reactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM).

Discussion: The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

No MeSH data available.


Related in: MedlinePlus

Plausible mechanism for the formation of pyrano[2,3]pyrimidine dione derivatives 4.
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C2: Plausible mechanism for the formation of pyrano[2,3]pyrimidine dione derivatives 4.

Mentions: A reasonable mechanism for the formation of the product 4 is outlined in Scheme 2. First the oxygen of carbonyl group in benzaldehyde 2 was protonated and malonitrile 3 tautomerized to 6. The Knoevenagel condensation of compounds 5 and 6 was occurred to form the cyano-olefin 8. Subsequently, the tautomerized barbituric acid 7 endures nucleophilic attack to 8 and gives the Michael adduct 9. The intermediate 9 tautomerizes in the presence of acidic catalyst to generate intermediate 10 which cyclizes to give compound 11 which subsequently tautomerized to afford the fully aromatized compound 4.


Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H) and their docking and urease inhibitory activity.

Ziarani GM, Faramarzi S, Asadi S, Badiei A, Bazl R, Amanlou M - Daru (2013)

Plausible mechanism for the formation of pyrano[2,3]pyrimidine dione derivatives 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3584946&req=5

C2: Plausible mechanism for the formation of pyrano[2,3]pyrimidine dione derivatives 4.
Mentions: A reasonable mechanism for the formation of the product 4 is outlined in Scheme 2. First the oxygen of carbonyl group in benzaldehyde 2 was protonated and malonitrile 3 tautomerized to 6. The Knoevenagel condensation of compounds 5 and 6 was occurred to form the cyano-olefin 8. Subsequently, the tautomerized barbituric acid 7 endures nucleophilic attack to 8 and gives the Michael adduct 9. The intermediate 9 tautomerizes in the presence of acidic catalyst to generate intermediate 10 which cyclizes to give compound 11 which subsequently tautomerized to afford the fully aromatized compound 4.

Bottom Line: The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate.Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity.Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chemistry, Alzahra University, Vanak Square, P,O, Box 19938939973, Tehran, Iran. gmziarani@hotmail.com.

ABSTRACT

Background: A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.

Results: Reactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM).

Discussion: The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

No MeSH data available.


Related in: MedlinePlus