New annulated pyrano[2,3-d]pyrimidine derivatives were synthesized with hydroxyl, methoxy, bromine, nitrile and nitro substituents on its skeleton. The correlated electronic effect of substituents on the magnitude of antibacterial activity was noted. The electron donating substituents (namely; 4–OH, 4–OCH₃, 4-Br) and electron withdrawing substituents (4-NO₂) on phenyl ring in the pyrano[2,3-d]pyrimidine skeleton exerted different influence on its antimicrobial activity against some Gram-positive and Gram-negative bacteria such as Pseudomonas aureus, E. coli, Staphylococcus aureus, Klebsiella pneumonia and Bacillus cereus. All the pyrano[2,3-d]pyrimidines were characterized by spectroscopic analyses. Antibacterial screening revealed that the presence of heteroaryl, cyano and amino groups on pyrano[2,3-d]pyrimidine skeleton increases its penetrating power on the bacterial cell wall so that the product becomes more biologically active. So the the nature of electron withdrawing or electro-donnor Impact of substituents should be taken in consideration in drug design.

Hydrolysis of -CRN to amide restored vital Intramolecular interaction like ortho-nitrophenyl and -ONO^δ-...-NH^δ+/amide link, offering a crucial template for antibacterial -NH, HO-pharmacophore sites, which ultimately elevated innate antimicrobial profiles. POM combinatorial analysis of tangible electronic contributions due to armed annulated pyrano[2,3-d]pyrimidines concluded their broad antimicrobial activity and viable/prominent drug score index through perspective parameters particularly: inter atomic distance/linkers, steric, electronic, polar parameters, and with a different polarising effect of electron donating/withdrawing environments of substituents. Furthermore, an anti-Kinase pharmacophore site (-O=CNH-C=O) was evaluated in continuation of the POM investigations. All synthesized products verified fewer side effects than standard streptomycin, but facile implication in selective cancer media (viz. breast or leucemia still needs to be screened).

合成了新的环状吡喃并[2,3-d]嘧啶衍生物，其骨架上带有羟基、甲氧基、溴、腈和硝基取代基。注意到取代基对抗菌活性大小的相关电子效应。吡喃并[2,3-d]嘧啶骨架中苯环上的给电子取代基（即：4-OH、4-OCH ₃、4-Br）和吸电子取代基（4-NO ₂）对其产生不同的影响。对一些革兰氏阳性和革兰氏阴性细菌如金黄色葡萄球菌、大肠杆菌、金黄色葡萄球菌、肺炎克雷伯菌和蜡状芽孢杆菌的抗菌活性。所有吡喃并[2,3-d]嘧啶均通过光谱分析表征。抗菌筛选表明，吡喃并[2,3-d]嘧啶骨架上杂芳基、氰基和氨基的存在增加了其对细菌细胞壁的渗透能力，从而使产物变得更具生物活性。因此在药物设计中应考虑吸电子或供电子体的性质对取代基的影响。

-CRN 水解为酰胺恢复了重要的分子内相互作用，如邻硝基苯基和 -ONO ^δ- ...-NH ^δ+/酰胺链接，为抗菌-NH、H2O-药团位点提供了关键模板，最终提高了先天抗菌谱。由于武装环状吡喃并 [2,3-d] 嘧啶对有形电子贡献的 POM 组合分析得出了它们广泛的抗菌活性和可行/突出的药物评分指数，特别是通过透视参数：原子间距离/连接器、空间、电子、极性参数，并且具有不同的取代基给电子/吸电子环境的极化效应。此外，在 POM 研究的继续过程中评估了抗激酶药效团位点 (-O=CNH-C=O)。所有合成的产品都证实比标准链霉素的副作用更少，但在选择性癌症培养基中容易产生影响（即仍需要筛选乳腺癌或白血病）。