**6. Pyrimido-pyrimidines**

In view of the various physiological properties, the pyrimido[4,5-*d*]pyrimidines were generally prepared from derivatives of enamines [34, 35]. Various substituted 2-amino-6,8-diaryl-5-oxo-pyrimido[4,5-*d*]pyrimidin-7-thiones (**14**) in 62–75% overall yields can be synthesized by reacting the respective compounds **2** with guanidine nitrate in the presence of sodium methoxide and methanol (**Figure 6**) [36]. Similarly, the condensation products **3** were reacted with guanidine nitrate in sodium methoxide and methanol affording the corresponding substituted 3,4-dihydro-5-oxopyrimido[4,5-*d*] pyrimidine-7-thiones, **15** in good yields (**Figure 6**) [36].

The derivatives of pyrimido-pyrimidines are quite effective in the inhibition of cancer cell sickness [37], exhibition of diuretic activities and anti-inflammatory activities [38]. The antifungal activity for the compounds **14** and **15** was screened against *Aspergillus niger* at different concentrations by agar growth paper disc method using Czapeck's nutrient medium and DMF was used as control. The average percentage inhibition after 96 hr. was determined and the results were compared with those obtained using commercial fungicide Carbendazim. Most of the compounds were found to be fairly active at the concentrations of 1000 ppm comparable with standard fungicide. It is noteworthy that introduction of pyrimido moiety in the pyrimidine nucleus enhances the fungitoxicity to some extent and furthermore,

*Construction of Biologically Active Five- and Six-Membered Fused Ring Pyrimidine Derivatives… DOI: http://dx.doi.org/10.5772/intechopen.108842*

**Figure 7.** *Synthesis of thioxo pyrimido[4,5-d]pyrimidinone derivatives.*

chloro-substituted heterocycles (**14c** and **15c**) were more active than methyl-substituted compounds (**14b** and **15b**).

Many of the earlier methods reported for the syntheses of pyrimido[4,5-*d*]pyrimidine derivatives require toxic chemicals, long reaction times, afford low to moderate yields and require many steps. A simple one-pot method for the synthesis of thioxo pyrimido[4,5-*d*]pyrimidinone derivatives by treatment of *N*,*N*-diethylthiobarbituric acids, benzaldehydes and thiourea/urea with NaOEt as the catalyst under solvent-free conditions was reported (**Figure 1**). Several 5-aryl-2,7-dithioxo-pyrimido[4,5-d] pyrimidine-4-ones; 4-aryl-7-thioxo-pyrimido[4,5-d]pyrimidine-2,5-diones were synthesized using an eco-friendly and efficient, multi-component reaction (MCR) under solvent free conditions. The reactions proceed *via* Biginelli type condensation of aromatic aldehyde, thiobarbituric acid and urea or thiourea in presence of catalytic amount of NaOEt. The synthesized compounds were screened for anti-inflammatory activity. It was observed that the compounds containing fluoro-substituents gave good yields and showed high anti-inflammatory activities. There are no reports available on the formation of Biginelli products using NaOEt as a catalyst under solventfree conditions (**Figure 7**).
