**3. Synthetic methods in decorated pyrimidine core**

A diverse group of drugs or drug candidates comprise pyrimidine core. The instances elaborated below belong to recently FDA approved ones or with special medical interest.

#### **3.1 Synthesis of N-2,4-Disubstitited pyrimidines**

Polyamino-pyrimidines play a very important role in biological and pharmaceutical chemistry. 2,4- diamino-pyrimidine derivatives as potential antimalarial agents [17], SNSR4 antagonists [47], antitumor agents [48] and caspase-1 inhibitors [49]. This report focused on the method development for the synthesis of the latter class of compounds.

*Synthetic Approaches for Pharmacologically Active Decorated Six-Membered Diazines DOI: http://dx.doi.org/10.5772/intechopen.109103*

#### **Figure 1.**

*Examples of chemical structures of bioactive pyrimidine-based derivatives. Pyrimidine heterocyclic rings found in potent anti-HIV agents like zidovudine (1), Stavudine (2); antiviral like Trifluridine (8), Emtricitabine (9, 15); antifungal like Voriconazole (11) Flucytosine (Ancobon) (10); antihistamine H4 receptor (12 and 13), antibacterial (16), cholesterol lowering agent Rosuvastatin (Crestor) (17); antitumor agents like fluorouracil (3), Tegafur (4), Carmofur (5), 5-Fluorouridine (6), Capecitabine (7), ENMD-2076 (14), Imatinib (18), Nimustine (19), Monastrol (20), Pazopanib (21), Brigatinib (22), Spebrutinib (23), Ceritinib (24), AP26113 (25), Spebrutinib (26), phosphoryl derivative (pho-DPPYs) (27), Rociletinib (28), Osimertinib (29), Olmutinib (30), Remibrutinib (LOU064) (31), Evobrutinib (32), Vecabrutinib (34).*

Polysubstituted pyrimidines received sub- special attention due to their pronounced physiological activity.

#### *3.1.1 Synthesis of N-2,4-Disubstituted N-2,4,5-trisubstituted pyrimidines*

#### *3.1.1.1 Approaches for synthesis of N-2,4-disubstituted pyrimidines*

2,4-disubstited pyrimidines are classifies according to the type of bond linking the substituent to the core heterocycle: i) 2,4-diamminosubstituted (2,4-diN), ii) 2,4monoaminomonocarbon (2 N, 4C), iii) 2,4-dicarbon (2,4-diC), iv) 2,4 monoaminomonooxo (2 N, 4O), v) 2,4-monoaminomonothio (2 N, 4S), vi) 2,4 monothiomonoamino (2S, 4 N), vii) 2,4-monothiomonocarbo (2S, 4C) and so on. Substituents reported so far can be aromatic, aliphatic, heteroaromatic and heteroaliphatic.
