A direct new synthetic method on the chemistry of benzo[g]pteridines is reported. Reactions between 5,8-dichloro-2,3-dicyanoquinoxaline and benzamidines gave 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines in high to quantitative yields. The molecular structure of an N-acetyl derivative of a member of this family of compounds, 4-acetamido-6,9-dichloro-2-phenylbenzo[g]pteridine, was determined by X-ray crystallography. The synthesized compounds were evaluated for their potential anti-inflammatory activity as inhibitors of the pro-inflammatory cytokines TNF-α and IL-6. Compounds 5b, 5d and 5i showed the highest level of inhibition of both cytokines. The rest of the compounds into the series (5a, 5f, 5g and 5h), with the only exceptions of compounds 5c and 5e, which were unable to inhibit TNF-α and were the two compounds with the lower effect upon IL-6, were also able to reach good levels of inhibition of TNF-α and even higher levels of inhibition of IL-6.