Reasearch Awards nomination

Email updates

Keep up to date with the latest news and content from DARU Journal of Pharmaceutical Sciences and BioMed Central.

Open Access Highly Accessed Research article

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

Ghodsi Mohammadi Ziarani1*, Sakineh Faramarzi1, Shima Asadi1, Alireza Badiei2, Roya Bazl3 and Massoud Amanlou3*

Author Affiliations

1 Department of Chemistry, Alzahra University, Vanak Square, P.O. Box 19938939973, Tehran, Iran

2 School of Chemistry, College of Science, University of Tehran, Tehran, Iran

3 Drug Design and Development Research Center and Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

For all author emails, please log on.

DARU Journal of Pharmaceutical Sciences 2013, 21:3  doi:10.1186/2008-2231-21-3

The electronic version of this article is the complete one and can be found online at:

Received:12 September 2012
Accepted:30 December 2012
Published:5 January 2013

© 2013 Mohammadi Ziarani et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



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.


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).


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.

SBA-Pr-SO3H; Barbituric acid; Pyrano[2,3-d]pyrimidine diones; Multicomponent reaction (MCRs); Urease inhibitory


Pyran derivatives are ordinary structural subunits in a variety of important natural products, including carbohydrates, alkaloids, polyether antibiotics, pheromones, and iridoids [1]. Uracil and its fused derivatives, such as pyrano[2,3-dpyrimidines, pyrido[2,3-dpyrimidines or pyrimido[4,5-dpyrimidines are well recognized by synthesis as well as biological chemists.

These annelated uracils have received considerable attention over the past years due to their wide range of biological activity. Compounds with these ring systems have diverse pharmacological properties such as antiallergic [2], antihypertensive [3], cardiotonic [4], bronchiodilator [5], antibronchitic [6], or antitumour activity [7]. The synthesis of the mentioned compounds containing a pyran and an uracil ring poses significant synthetic challenges. Therefore, for the preparation of these complex molecules large efforts have been directed towards the synthetic manipulation of uracils. As a result, a number of reports have described in literature [8-12] which usually require drastic conditions, long reaction times and complex synthetic pathways and the yields are poor. Thus new routes for the synthesis of these molecules have attracted considerable attention in search for a rapid entry to these heterocycles.

The general procedures for the preparation of pyrano[2,3-d pyrimidine-2,4(1H,3H)-diones include the reaction of arylidenemalononitriles with barbituric acid under traditional hot reaction conditions [13,14] or microwave irradiation [15]. In these methods the arylidenemalononitriles are previously derived from malononitrile and aldehydes. Recently, direct condensation of aldehydes, malononitrile and barbituric acid in aqueous media has been reported under ultrasound irradiation [16], or catalyzed by diammonium hydrogen phosphate [17].

Different catalysts such as L-proline [18], N-methylmorpholine [19], [BMIm]BF4[20], 1,4-dioxane [13,21], H14[NaP5W30O110[22] and [K Al(SO4)2[23] under heating also 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) [17] and L-proline [24] under room temperature condition have been researched for the synthesis of pyrano[2,3-dpyrimidine diones derivatives. In addition, Et3N was examined under microwave irradiation [25]. The catalyst free procedures for the preparation of the pyrano pyrimidine diones were also investigated using microwave irradiation [15], ultrasonic [16], heating with water [26] and ball-milling technique [27].

Mesoporous materials are a special type of nanomaterials with ordered arrays of uniform nanochannels. These materials have important applications in a wide variety of fields such as separation, catalysis, adsorption, advanced nanomaterials, etc [28-33]. SBA-15 has many advantages such as: largest pore-size mesoporous material with highly ordered hexagonally arranged meso-channels, with thick walls, adjustable pore size from 3 to 30 nm, and high hydrothermal and thermal stability [34-38], therefore it is expected to be an useful catalyst in the synthesis of organic compounds.

The surface of SBA-15 was modified by acidic functional groups (e.g., -SO3H) to prepare nano-solid acid catalyst which can use in the synthesis of various heterocyclic compounds [35]. Recently, we have also reported the use of this catalyst for the synthesis of quinoxaline derivatives [39], polyhydroquinolines [40], triazoloquinazolinones and benzimidazoquinazolinones [41].

Moreover, to the best of our knowledge there is no report on the use of these materials as nanoreactors in the synthesis of pyrano pyrimidine diones derivatives. In the present work, we report our results on the research of convenient and green way for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives using SBA-Pr-SO3H as a nanocatalyst and their urease inhibitory activity was investigated.

Material and methods

Gc-Mass analysis was performed on a Gc-Mass model: 5973 network mass selective detector, Gc 6890 Agilent. IR spectra were recorded from KBr disk using a FT-IR Bruker Tensor 27 instrument. Melting points were measured by using the capillary tube method with an electro thermal 9200 apparatus. The 1H-NMR (250 MHZ) was run on a Bruker DPX, 250 MHZ. Nitrogen adsorption and desorption isotherms were measured at -196°C using a Japan Belsorb II system after the samples were vacuum dried at 150°C overnight. Surface areas were calculated by the Brunauer-Emmett-Teller (BET) method, and pore sizes were calculated by the Barrett-Joyner-Halenda (BJH) method. Thermogravimetry analysis (TGA) was carried out in Perkin Elmer Pyris Diamond instrument from ambient temperature to 800°C using 20°C/min ramp rate.

Preparation of catalyst

Synthesis and functionalization of SBA-15

The nanoporous compound SBA-15 was synthesized and functionalizaed according to our previous report and the modified SBA-15-Pr-SO3H was used as nanoporous solid acid catalyst in the following reactions [40-43].

General procedure for the preparation pyrano[2,3-d]pyrimidine diones

The SBA-Pr-SO3H (0.02 g) was activated in vacuum at 100°C and then after cooling to room temperature, barbituric acid (0.265 g, 2 mmol), 4-nitrobenzaldehyde (0.362 ml, 2.4 mmol) and malonitrile (0.132 g, 2 mmol) was added to the catalyst in a reaction vessel (Scheme 1). The reaction mixture was heated for 15 min in bath oil at 140°C. After the completion of reaction as indicated by TLC, the generated solid was recrystallized in DMF and ethanol to afford pure product 4. The resulting solid product was solved in DMF, and then filtered for removing the unsolvable catalyst and then the filtrate was cooled to afford the pure product as a solid. The spectroscopic and analytical data for selected compounds are presented in the following part. The catalyst was washed subsequently with acetonitrile, diluted acid solution, distilled water and then acetone, dried under vacuum and re-used for several times without loss of significant activity.

Scheme 1

Three-component synthesis of pyrano[2,3-d]pyrimidine dione derivatives.

Spectral data for product

7-Amino-6-cyano-5-(3-methylphenyl)-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones4f: IR (KBr): υmax= 3411 and 3320 (NH2), 2961 and 2740 (CN), 1733 and 1700 (C=O) cm-1. 1H NMR (250 MHz, CDCl3): δ = 2.47 (s, 3H, CH3), 4.13 (s, 1H, CH), 6.95-7.17 (m, 6H, ArH & NH2), 11.09 (s, 1H, NH) 12.00 (s, 1H, NH) ppm. Mass (m/z): 296 (M+), 285, 149 (100).

7-Amino-6-cyano-5-(3-methoxylphenyl)-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones4h: IR (KBr): υmax= 3183 and 2834 (NH2), 2246 and 2200 (CN), 1690 and 1538 (C=O), 1459, 1375 cm-1. 1H NMR (250 MHz, CDCl3): δ = 3.35 (s, 3H, OCH3), 4.16 (s, 1H, CH), 6.96-7.78 (m, 4H, ArH), 8.48 (s, 2H, NH2) 11.03 (s, 1H, NH), 11.77 (s, 1H, NH) ppm. Mass (m/z): 312 (M+), 276, 230, 215.

7-Amino-6-cyano-5-(2,6-dichlorophenyl)-5H-pyrano[2,3-d]pyrimidinone4k: IR (KBr): υmax= 3368, 3337, 3148 and 3038 (NH2), 2930 and 2196 (CN), 1703 and 1664 (C=O), 1102, 1283, 763 cm-1. 1H NMR (250 MHz, CDCl3): δ = 5.28 (s, 1H, CH), 7.94 (s, 2H, NH2), 7.24- 7.36 (m, 5H, -ArH & NH2), 11.05 (s, 1H, NH), 12.20 (s, 1H, NH) ppm. Mass (m/z): 352 (M+), 316, 282, 267, 257, 191, 167, 122, 82.

7-Amino-6-cyano-1,3-dimethyl-5-(4-Hydroxyphenyl)-1,5-dihydro-pyrano[2,3-d]pyrimidine-2,4-dione4l: IR (KBr): υmax= 3415, 3315, 3203 and 3020 (NH2), 2192 (CN), 1688, 1659 and 1529 (C=O), 1348 cm-1. 1H NMR (250 MHz, CDCl3): δ = 3.17 (s, 3H, CH3), 3.40 (s, 3H, CH3), 4.40 (s, 1H, CH), 6.83-8.25 (m, 6H, ArH, & NH2) ppm. Mass (m/z): 326 (M+), 327(M+1), 306, 281, 149 (100).

Docking approach

AutoDockTools 1.5.4 (ADT) [44], Autogrid 4.2 [45] and Autodock 4.2 [45] were used to prepare input files, calculate grid box and docking experiments. A grid map consisted of 40 × 40 × 40 Å points around the active site was used. The center of the grid was set to the average coordinates of the two Ni2+ ions in the α chain of H. pylori urease (pdb ID: 3LA4). A Lamarckian genetic algorithm (LGA) was used for the conformational search. The reliability of the applied docking protocol was assessed by re-docking acetohydroxamic acid (AHA) into the active site of the H. pylori urease. Each Lamarckian job consisted of 250 runs. The initial population was 150 structures, and the maximum number of energy evaluations and generations was 2.5 × 107. The other parameters were set to default values. The final structures were clustered and ranked according to the most favorable docking energy. This protocol was then similarly applied to all synthesized compounds [46].

Computational resources

The computational studies were carried out on a computer cluster comprising four sets of HP Prolient ML370-G5 tower servers equipped with two quad-core Intel Xeon E5355 processors (2.66 GHz) and 4 GB of RAM, running a Linux platform (SUSE 10.2).

Urease inhibitory assay

All the chemicals used were of analytical grade from Merck Co., Germany. All aqueous solutions were prepared in MilliQ (Millipore, USA) water. Jack-bean urease was obtained from Merck (5 units/mg). After proper dilution, the concentration of enzyme solution adjusts at 2 mg/ml which is determined by UV spectroscopy at λ = 280 nm. Urease activity was measured by rapid phenol red urease test contains phenol red 0.1% (w/v) and 100 mM urea in 10 mM phosphate buffer, pH 7.0. Based on this method, the colour change from yellow (pH 6.8) to bright pink (pH 8.2) of phenol red pH indicator as a result of urea hydrolysis to ammonia was measured. The urease activity of the synthesized compounds (10 μl in DMSO) was monitored spectrophotometrically at 560 nm after incubation at 37°C for 30 min [47].

Results and discussion

In this article, we want to report the use of SBA-Pr-SO3H as a nano and green solid acid catalyst and nano- reactor in the synthesis of 7-amino-6-cyano-5-aryl-5H-pyrano[2,3-d]pyrimidinones by the Knoevenagel–Michael condensation reaction. The procedure consisted of the mixture of malonitrile, aromatic aldehydes, and barbituric acid derivatives. The reaction proceeded in high yields in the presence of SBA-Pr-SO3H as catalyst at room temperature and solvent free conditions to obtain our desired products 4a-4l (Scheme 1).

First the suitable conditions for the above transformation are examined with various solvents in different temperatures in the presence of SBA-Pr-SO3H as nanocatalyst as shown in Table 1. The results revealed when the reaction proceeds in the absence of solvent, the desired product was obtained in high yield (90%) and very short reaction time. By increasing the temperature of the media to 130°C, the reaction time decreases to 15 minutes so the best reaction conditions were obtained (entry 5, Table 1). The same reaction was done without using any catalyst and a very low yield of product was obtained.

Table 1. Optimization of the reaction conditions in the synthesis of 4i

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.

Scheme 2

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

Table 2 shows the obtained results in the reaction of a series of representative aldehydes with malononitrile and barbituric derivatives. The most derivatives were obtained in short reaction time ranging 5-45 minutes in high to very high yields. The effect of substituents on the aromatic ring did not show special effects in terms of yields under these reaction conditions.

Table 2. Synthesis of pyrano[2,3-d]pyrimidine diones derivatives 4 under optimized conditions

Literature surveys revealed that various conditions have been employed in this reaction as demonstrated in Table 3. The results illustrated that SBA-Pr-SO3H was an efficient catalyst in the synthesis of these compounds.

Table 3. Comparison of SBA-Pr-SO3H and various catalysts in the synthesis of pyrano[2,3-d]pyrimidine diones derivatives 4

Preparation of catalyst

Pure Nanoporous compound SBA-15 was synthesized according to the well-established method designed by Zhao & coworkers [42] with triblock poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) copolymer (Pluronic, EO20PO70EO20, P123) as the template. The SBA-15 silica was functionalized with (3-mercaptopropyl)trimethoxysilane (MPTS) and then, the thiol groups were oxidized to sulfonic acid by hydrogen peroxide. Analyzing of the catalyst surface was performed by various methods such as TGA, BET and CHN methods which demonstrated that the propylsulfonic acids were immobilized into the pores. Calculating average pore diameter of the surface area was performed by the BET method and pore volume of SBA-Pr-SO3H are 440 m2 g-1, 6.0 nm and 0.660 cm3 g-1, respectively, which are smaller than those of SBA-15 due to the immobilization of sulfonosilane groups into the pores [40]. The TGA analysis of SBA-Pr-SO3H confirmed the amount of organic groups on SBA-15. The weight reduction of SBA-Pr-SO3H in the temperature range between 200-600°C indicated that the amount of organic group was 1.2 mmol/g. SEM image of SBA-Pr-SO3H (Figure 1a) shows uniform particles about 1μm. The same morphology was observed for SBA-15. It can be concluded that morphology of acid catalyst was saved without change during the surface modifications. On the other hand, the TEM image (Figure 1b) reveals the parallel channels, which resemble to the pores configuration of SBA-15. This indicates that the pore of SBA-Pr-SO3H was not collapsed during two steps reactions.

thumbnailFigure 1. (a) SEM and (b) TEM images of SBA-Pr-SO3H.

The pyrano[2,3-dpyrimidine diones structurally similar to barbituric acids. The antibacterial and urease inhibitory activity of barbituric acid derivatives were reported [46,48,49]. Many urease inhibitors have been synthesized and tested, but because of their toxicity and instability use of them in vivo is impossible [48-50]. Thus, the search is still on for finding strong and specific urease inhibitors.

As shown in Table 4, all prepared pyrano[2,3-d]pyrimidine diones are demonstrated different profile of activity. This might be due to similarity of synthesised compounds to substrate of enzyme. While compounds 4a, 4d and 4l were not active in urease inhibition test, compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, show good inhibitory activity (Table 4). These compounds with electron donating group and subsequent hydrophobic interaction with active site of enzyme prevents the hydrolysis of substrate. Electron withdrawing groups such as nitro, 3-methoxy reduced urease inhibitory activity due to decreasing partial charge on nitrogen atoms of barbiturate moiety on pyrano[2,3-d]pyrimidine ring which is essential for inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl groups will convert the inhibitor to activator.

Table 4. Urease inhibitory activities (IC50 in μM) and interaction energies (kcal mol−1) of pyrano[2,3-d]pyrimidine diones derivatives 4


In conclusion we have developed a nano-catalyzed multicomponent synthesis of pyrano pyrimidine diones in good to very good yields. In comparison with previous investigations (Table 3), we presented SBA-Pr-SO3H as an efficient and active nano-reactor (Figure 2). Our method is simple as no special apparatus, reagents or chemicals, and work up are required, and the formed compound is filtered and purified just by simple crystallization. This synthesis is also advantageous in terms of atom economy as well as is devoid of any hazardous chemicals. The urease inhibitory activity of pyrano[2,3-d]pyrimidine dione derivatives were reported for first time.

thumbnailFigure 2. SBA-Pr-SO3H act as a nano-reactor in this reaction.

Competing interest

The authors declare that they have no competing of interests related to this publication.

Authors’ contributions

GMZ: Collaboration in design and identifying of the structures of target compounds, manuscript preparation. SF: Synthesis of the intermediates and some target compounds. SA: Synthesis of some target compounds and collaboration in identifying of the structures of target compounds. AB: Synthesis and characterization of nano catalyst. RB: Collaboration in docking study and evaluation of urease inhibitory test. MA: Collaboration in design of docking study, management of urease test and manuscript preparation. All authors read and approved the final manuscript.


We gratefully acknowledge for financial support from the Research Council of Alzahra University and University of Tehran and Tehran University of Medical Sciences.


  1. Tietze LF, Kettschau G: In Topics in Current Chemistry. In Volume 189. Berlin: Springer; 1997:1-120. OpenURL

  2. Kitamura N, Onishi A: Eur. Pat. 163599 (1984).

    Chem Abstr 1984, 104:186439. OpenURL

  3. Furuya S, Ohtaki T: Pyridopyrimidine derivatives, their production and use. Eur Pat Appl EP 608565 (1994).

    Chem Abstr 1994, 121:205395w. OpenURL

  4. Heber D, Heers C, Ravens U: Positive inotropic activity of 5-amino-6-cyano-1, 3-dimethyl-1, 2, 3, 4-tetrahydropyrido [2, 3-d] pyrim idine-2, 4-dione in cardiac muscle from guinea-pig and man. Part 6: compounds with positive inotropic activity.

    Die Pharmazie 1993, 48:537-541. PubMed Abstract OpenURL

  5. Coates WJ: Pyrimidopyrimidine Derivatives. Eur Pat 351058.

    Chem Abstr 1990, 113:40711. OpenURL

  6. Sakuma Y, Hasegawa M, Kataoka K, Hoshina K, Yamazaki N, Kadota T, Yamaguchi H: 1, 10-Phenanthroline Derivatives. WO 91/05785 PCT Int. Appl., 1989 May 2.

    Chem Abstr 1991, 115:71646. OpenURL

  7. Broom AD, Shim JL, Anderson GL: Pyrido [2,3-d] pyrimidines. IV. Synthetic studies leading to various oxopyrido [2,3-d] pyrimidines.

    J Org Chem 1976, 41:1095-1099. PubMed Abstract | Publisher Full Text OpenURL

  8. Srivastava P, Saxena AS, Ram VJ: An elegant approach towards the regioselective synthesis of deazalumazines through nucleophile induced ring transformation reactions of 6-aryl-3-cyano-4-methylthio-2h-pyran-2-ones.

    Synthesis 2000, 541-544. OpenURL

  9. Hirota K, Kuki H, Maki Y: Novel synthesis of pyrido[3,4-d]pyrimidines, pyrido[2,3-d]pyrimidines, and quinazolines via palladium-catalyzed oxidative coupling.

    Heterocycles 1994, 37:563-570. Publisher Full Text OpenURL

  10. Ahluwalia VK, Kumar R, Khurana K, Batla R: A convenient synthesis of 1,3-diaryl-1,2,3,4,-tetrahydro-5,7,7-trimethyl-4-oxo-2-thioxo-7H-pyrano[2 ,3-d ]pyrimidines.

    Tetrahedron 1990, 46:3953-3963. Publisher Full Text OpenURL

  11. Wamhoff H, Muhr J: Reactions of uracils; 15. 7-Ethoxypyrimido[4,5-d]pyrimidines via a uracil-carbodiimide derivative and their products of aminolysis and pyrolysis.

    Synthesis 1988, 11:919-921. OpenURL

  12. Ahluvalia VK, Sharma HR, Tyagi R: A novel one step synthesis of pyrano (2,3-d) pyrimidines.

    Tetrahedron 1986, 42:4045-4048. Publisher Full Text OpenURL

  13. Sharanin YA, Klokol GV: Nitrile cyclization reactions. XVI. Reaction of arylidene drivatives of malononitrile and ethyl cyanoacetate with barbituric acid.

    Zh Org Khim 1984, 20:2448-2452. OpenURL

  14. Ibrahim MKA, El-Moghayar MRH, Sharaf MAF: Activated nitriles in heterocyclic synthesis: a novel synthesis of pyrano[2,3-d]pyrimidine, pyrano[2,3-c]pyrazole, pyrano[2,3-d]thiazole, and thiazolo[3,2-a]pyridine drivatives.

    Indian J Chem Sect B 1987, 26B:216-219. OpenURL

  15. Gao Y, Tu S, Li T, Zhang X, Zhu S, Fang F, Shi D: Effective synthesis of 7-amino-6-cyano-5-aryl-5H-pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones under microwave irradiation.

    Synth Commun 2004, 34:1295-1299. Publisher Full Text OpenURL

  16. Jin TS, Liu LB, Tu SJ, Zhao Y, Li TS: Clean one-pot synthesis of 7-amino-5-aryl-6-cyano-1,5-dihydro-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-diones in aqueous media under ultrasonic irradiation.

    J Chem Res 2005, 3:162-163. OpenURL

  17. Balalaie S, Abdolmohammadi S, Bijanzadeh HR, Amani AM: Diammonium hydrogen phosphate as a versatile and efficient catalyst for the one-pot synthesis of pyrano[2,3-d]pyrimidinone derivatives in aqueous media.

    Mol Divers 2008, 12:85-91. PubMed Abstract | Publisher Full Text OpenURL

  18. Heravi MM, Ghods A, Bakhtiari K, Derikvand F: Zn[(L)proline]2: an efficient catalyst for the synthesis of biologically active pyrano[2,3-d]pyrimidine derivatives.

    Synth Commun 2010, 40:1927-1931. Publisher Full Text OpenURL

  19. Shestopalov AA, Rodinovskaya LA, Shestopalov AM, Litvinov VP: One-step synthesis of substituted 4,8-dihydropyrano[3,2-b]pyran-4-ones.

    Russ Chem Bull 2004, 53:724-725. OpenURL

  20. Yu J, Wang H: Green synthesis of pyrano[2,3‐d]‐pyrimidine derivatives in ionic liquids.

    Synth Commun 2005, 35:3133-3140. Publisher Full Text OpenURL

  21. Zoorob HH, Abdelhamid M, El-Zahab MA, Abdel-Mogib M, AMA I: 1, 3-Dimethylpyrimidoheterocycles as antibacterial agents.

    Arzneim Forsch 1997, 47:958-962. OpenURL

  22. Heravi MM, Ghods A, Derikvand F, Bakhtiari K, Bamoharram FF: H14[NaP5W30O110] catalyzed one-pot three-component synthesis of dihydropyrano[2,3-c]pyrazole and pyrano[2,3-d]pyrimidine derivatives.

    J Iran Chem Soc 2010, 7:615-620. Publisher Full Text OpenURL

  23. Mobinikhaledi A, Foroughifar N, Bodaghi Fard MA: Eco-friendly and efficient synthesis of pyrano[2,3-d] pyrimidinone and tetrahydrobenzo[b]pyran derivatives in water.

    Synth React Inorg, Met-Org, Nano-Met Chem 2010, 40:179-185. OpenURL

  24. Bararjanian M, Balalaie S, Movassagh B, Amani AM: One-pot synthesis of pyrano[2,3-d]pyrimidinone derivatives catalyzed by L-proline in aqueous media.

    J Iran Chem Soc 2009, 6:436-442. Publisher Full Text OpenURL

  25. Devi I, Kumar BSD, Bhuyan PJ: A novel three-component one-pot synthesis of pyrano[2,3-d]pyrimidines and pyrido[2,3-d]pyrimidines using microwave heating in the solid state.

    Tetrahedron Lett 2003, 44:8307-8310. Publisher Full Text OpenURL

  26. Shaabani A, Samadi S, Rahmati A: One-pot, three-component condensation reaction in water: an efficient and improved procedure for the synthesis of pyran annulated heterocyclic systems.

    Synth Commun 2007, 37:491-499. Publisher Full Text OpenURL

  27. Mashkouri S, Naimi-Jamal MR: Mechanochemical solvent-free and catalyst-free one-pot synthesis of pyrano[2,3-d]pyrimidine-2,4(1H,3H)-diones with quantitative yields.

    Molecules 2009, 14:474-479. PubMed Abstract | Publisher Full Text OpenURL

  28. Kresge CT, Leonowicz ME, Roth WJ, Vartuli JC, Beck JS: Ordered mesoporous molecular sieves synthesized by a liquid crystal template mechanism.

    Nature 1992, 359:710-712. Publisher Full Text OpenURL

  29. Tanev PT, Pinnavaia TJ: A neutral templating route to mesoporous molecular sieves.

    Science 1995, 267:865-867. PubMed Abstract | Publisher Full Text OpenURL

  30. Tanev PT, Chibwe M, Pinnavaia TJ: Titanium-containing mesoporous molecular sieves for catalytic oxidation of aromatic compounds.

    Nature 1994, 368:321-323. PubMed Abstract | Publisher Full Text OpenURL

  31. Bagshaw SA, Pinnavaia TJ: Templating of mesoporous molecular sieves by nonionic polyethylene oxide surfactants.

    Science 1995, 268:1242-1244. OpenURL

  32. Attard GS, Glyde JC, Goliner CG: Liquid-crystalline phases as templates for the synthesis of mesoporous silica.

    Nature 1995, 378:366-368. Publisher Full Text OpenURL

  33. Huo QS, Leon R, Petroff PM, Stucky GD: Mesostructure design with gemini surfactants: supercage formation in a three-dimensional hexagonal array.

    Science 1995, 268:1324-1327. PubMed Abstract | Publisher Full Text OpenURL

  34. Zhao DY, Feng JP, Huo QS, Melosh N, Fredrickson GH, Chmelka BF, Stucky GD: Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 angstrom pores.

    Science 1998, 279:548-552. PubMed Abstract | Publisher Full Text OpenURL

  35. Zhao DY, Huo QS, Feng JP, Chmelka BF, Stucky GD: Nonionic triblock and star diblock copolymer and oligomeric surfactant syntheses of highly ordered, hydrothermally stable, mesoporous silica structures.

    J Am Chem Soc 1998, 120:6024-6036. Publisher Full Text OpenURL

  36. Zhao DY, Sun JY, Li QZ, Stucky GD: Morphological control of highly ordered mesoporous silica SBA-15.

    Chem Mater 2000, 12:275-279. Publisher Full Text OpenURL

  37. Newalkar BL, Komarneni S, Katsuki H: Rapid synthesis of mesoporous SBA-15 molecular sieve by a microwave–hydrothermal process.

    Chem Commun 2000, 23:2389-2390. OpenURL

  38. Madhugiri S, Dalton A, Gutierrez J, Ferraris JP, Balkus KJ: Electrospun MEH-PPV/SBA-15 composite nanofibers using a dual syringe method.

    J Am Chem Soc 2003, 125:14531-14538. PubMed Abstract | Publisher Full Text OpenURL

  39. Mohammadi Ziarani G, Badiei A, Haddadpour M: Application of sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H) for one-pot synthesis of quinoxaline derivatives.

    Int J Chem 2011, 3:87-94. OpenURL

  40. Mohammadi Ziarani G, Badiei A, Khaniania Y, Haddadpour M: One Pot synthesis of polyhydroquinolines catalyzed by sulfonic acid functionalized SBA-15 as a New nanoporous acid catalyst under solvent free conditions.

    Iran J Chem Chem Eng 2010, 29:1-10. OpenURL

  41. Mohammadi Ziarani G, Badiei A, Aslani Z, Lashgari N: Application of sulfonic acid functionalized nanoporous silica (SBA-Pr-SO3H) in the green one-pot synthesis of triazoloquinazolinones and benzimidazoquinazolinones.

    Arabian J Chem

    in press

    Publisher Full Text OpenURL

  42. Zhao DHQ, Feng J, Chmelka BF, Stucky GD: Nonionic triblock and star diblock copolymer and oligomeric sufactant syntheses of highly ordered, hydrothermally stable, mesoporous silica structures.

    J Am Chem Soc 1998, 120:6024-6036. Publisher Full Text OpenURL

  43. Mohammadi Ziarani G, Badiei A, Shakiba Nahad M, Hassanzadeh M: Application of SBA-Pr-SO3H in the synthesis of benzoxazole derivatives.

    Eur J Chem 2012, 3:433-436. Publisher Full Text OpenURL

  44. Sanner MF: Python: a programming language for software integration and development.

    J Mol Graph Model 1999, 17:57-61. PubMed Abstract OpenURL

  45. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ: AutoDock4 And AutoDockTools4: automated docking with selective receptor flexibility.

    J Comput Chem 2009, 30:2785-2791. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  46. Azizian H, Nabati F, Sharifi A, Siavoshi F, Mahdavi M, Amanlou M: Large-scale virtual screening for the identification of new helicobacter pylori urease inhibitor scaffolds.

    J Mol Model 2012, 18:2917-2927. PubMed Abstract | Publisher Full Text OpenURL

  47. Quintana-Guzman EM, Schosinsky-Nevermann K, Arias-Echandy M, Davidovich Rose H: Comparative study of urease tests for helicobacter pylori detection in gastric biopsies.

    Rev Biomed 1999, 10:145-151. OpenURL

  48. Chandrashekhar C, Latha K, Vagdevi H, Vaidya V: Synthesis and antimicrobial activity of chalcones of naphtho [2, 1-b] furan condensed with barbituric acid.

    Der Pharma Chemica 2011, 3:329-333. OpenURL

  49. Yan Q, Cao R, Yi W, Chen Z, Wen H, Ma L, Song H: Inhibitory effects of 5-benzylidene barbiturate derivatives on mushroom tyrosinase and their antibacterial activities.

    Eur J Med Chem 2009, 44:4235-4243. PubMed Abstract | Publisher Full Text OpenURL

  50. Khan KM, Ali M, Wadood A, Khan M, Lodhi MA, Perveen S, Choudhary MI, Voelter W: Molecular modeling-based antioxidant arylidene barbiturates as urease inhibitors.

    J Mol Graphics Modell 2011, 30:153-156. OpenURL